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Gene Information
Gene symbol: MC4R
Gene name: melanocortin 4 receptor
HGNC ID: 6932
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 9047307 | Arg85, Pro86, and Pro89 are important for selective inhibition of binding between MC1-R and MC3-R and MC4-R as their apparent K(I) values are essentially unchanged at MC1-R, while they have increased 6-10-fold relative to wild-type protein at MC3-R and MC4-R. |
| 2 | 9096167 | In vitro, in heterologous cells expressing either rat MC3-R or MC4-R, the major MCR subtypes expressed in brain, SHU-9119 showed no intrinsic agonism, but it inhibited alpha-MSH-induced cAMP accumulation (IC50 = 0.48 +/- 0.19 and 0.41 +/- 0.28 nM, respectively) and [125I]-[Nle4,DPhe7]-alpha-MSH binding (IC50 = 1.0 +/- 0.1 and 0.9 +/- 0.3 nM, respectively). |
| 3 | 9218248 | MCR are also found in melanocytic cells and adrenal cortical cells, the classical targets for alpha-MSH and ACTH, respectively, in myelogenous and lymphoid tissues, and in various endocrine and exocrine glands, adipocytes, and in autonomic ganglia. |
| 4 | 9218248 | A group of five G-protein-associated MCR subtypes, each of which is positively coupled to adenylate cyclase, has been identified. |
| 5 | 9218248 | Among these, the adrenal ACTH receptor (MC2-R) is selectively activated by ACTH. |
| 6 | 9218248 | In contrast, the other MCR subtypes (MC1-R, MC3-R, MC4-R, MC5-R) recognize a common group of ligands that includes various forms of MSH as well as ACTH; nevertheless they do exhibit important differences in ligand selectivity. |
| 7 | 9218248 | Moreover, spontaneous dominant mutations of the agouti gene in several strains of mice lead to its ubiquitous overexpression and produces not only yellow coat color, but also obesity and insulin resistance, perhaps as a result of its antagonism of other MCR subtypes. |
| 8 | 10070149 | Rats were fasted overnight to promote feeding behavior, then injected intraperitoneally with LPS (100 micrograms/kg ip), followed 30 min later by intracerebroventricular injection of either alpha-MSH or the melanocortin receptor subtype 3/subtype 4 (MC3-R/MC4-R) antagonist SHU-9119. |
| 9 | 10070149 | Central MC3-R/MC4-R blockade did not affect Tb or food intake in the absence of LPS treatment, but it reversed the LPS-induced reduction in 24-h food intake and increased LPS-induced fever without altering the LPS-induced suppression of locomotion. |
| 10 | 10070149 | Rats were fasted overnight to promote feeding behavior, then injected intraperitoneally with LPS (100 micrograms/kg ip), followed 30 min later by intracerebroventricular injection of either alpha-MSH or the melanocortin receptor subtype 3/subtype 4 (MC3-R/MC4-R) antagonist SHU-9119. |
| 11 | 10070149 | Central MC3-R/MC4-R blockade did not affect Tb or food intake in the absence of LPS treatment, but it reversed the LPS-induced reduction in 24-h food intake and increased LPS-induced fever without altering the LPS-induced suppression of locomotion. |
| 12 | 10078851 | Absence of genetic variation in some obesity candidate genes (GLP1R, ASIP, MC4R, MC5R) among Pima indians. |
| 13 | 10193863 | Agouti protein is normally expressed in hair follicles to regulate pigmentation through antagonism of the melanocortin-1 receptor, but in-vitro studies have demonstrated that the hormone also has potent antagonist activity for the melanocortin-4 receptor (MC4-R). |
| 14 | 10193863 | Additional studies with peptide antagonists have now implicated the MC4-R in the leptin signalling pathway. |
| 15 | 10193863 | Agouti protein is normally expressed in hair follicles to regulate pigmentation through antagonism of the melanocortin-1 receptor, but in-vitro studies have demonstrated that the hormone also has potent antagonist activity for the melanocortin-4 receptor (MC4-R). |
| 16 | 10193863 | Additional studies with peptide antagonists have now implicated the MC4-R in the leptin signalling pathway. |
| 17 | 10334300 | Altered energy balance causes selective changes in melanocortin-4(MC4-R), but not melanocortin-3 (MC3-R), receptors in specific hypothalamic regions: further evidence that activation of MC4-R is a physiological inhibitor of feeding. |
| 18 | 10334300 | We have examined the effects of underfeeding and obesity on the density of hypothalamic melanocortin MC3 and MC4 receptors (MC3-R and MC4-R, respectively), which may mediate the hypophagic effects of alpha-melanocyte-stimulating hormone (MSH) in the rat. |
| 19 | 10334300 | MC3-R and MC4-R were measured by quantitative autoradiography in brain sections using 125I-labeled Nle4-D-Phe7-alpha-MSH (125I-NDP-MSH) and discriminated by masking MC3-R with excess unlabelled gamma2-MSH. |
| 20 | 10334300 | We suggest that increased density of MC4-R with food restriction and in obese Zucker rats reflects receptor upregulation secondary to decreased release of alpha-MSH, consistent with increased hunger in these models. |
| 21 | 10334300 | Conversely, downregulation of MC4-R in diet-induced obesity may indicate increased alpha-MSH secretion in an attempt to limit overeating. |
| 22 | 10334300 | This alpha-MSH/MC4-R system may be inhibited by leptin and/or insulin. |
| 23 | 10334300 | Altered energy balance causes selective changes in melanocortin-4(MC4-R), but not melanocortin-3 (MC3-R), receptors in specific hypothalamic regions: further evidence that activation of MC4-R is a physiological inhibitor of feeding. |
| 24 | 10334300 | We have examined the effects of underfeeding and obesity on the density of hypothalamic melanocortin MC3 and MC4 receptors (MC3-R and MC4-R, respectively), which may mediate the hypophagic effects of alpha-melanocyte-stimulating hormone (MSH) in the rat. |
| 25 | 10334300 | MC3-R and MC4-R were measured by quantitative autoradiography in brain sections using 125I-labeled Nle4-D-Phe7-alpha-MSH (125I-NDP-MSH) and discriminated by masking MC3-R with excess unlabelled gamma2-MSH. |
| 26 | 10334300 | We suggest that increased density of MC4-R with food restriction and in obese Zucker rats reflects receptor upregulation secondary to decreased release of alpha-MSH, consistent with increased hunger in these models. |
| 27 | 10334300 | Conversely, downregulation of MC4-R in diet-induced obesity may indicate increased alpha-MSH secretion in an attempt to limit overeating. |
| 28 | 10334300 | This alpha-MSH/MC4-R system may be inhibited by leptin and/or insulin. |
| 29 | 10334300 | Altered energy balance causes selective changes in melanocortin-4(MC4-R), but not melanocortin-3 (MC3-R), receptors in specific hypothalamic regions: further evidence that activation of MC4-R is a physiological inhibitor of feeding. |
| 30 | 10334300 | We have examined the effects of underfeeding and obesity on the density of hypothalamic melanocortin MC3 and MC4 receptors (MC3-R and MC4-R, respectively), which may mediate the hypophagic effects of alpha-melanocyte-stimulating hormone (MSH) in the rat. |
| 31 | 10334300 | MC3-R and MC4-R were measured by quantitative autoradiography in brain sections using 125I-labeled Nle4-D-Phe7-alpha-MSH (125I-NDP-MSH) and discriminated by masking MC3-R with excess unlabelled gamma2-MSH. |
| 32 | 10334300 | We suggest that increased density of MC4-R with food restriction and in obese Zucker rats reflects receptor upregulation secondary to decreased release of alpha-MSH, consistent with increased hunger in these models. |
| 33 | 10334300 | Conversely, downregulation of MC4-R in diet-induced obesity may indicate increased alpha-MSH secretion in an attempt to limit overeating. |
| 34 | 10334300 | This alpha-MSH/MC4-R system may be inhibited by leptin and/or insulin. |
| 35 | 10334300 | Altered energy balance causes selective changes in melanocortin-4(MC4-R), but not melanocortin-3 (MC3-R), receptors in specific hypothalamic regions: further evidence that activation of MC4-R is a physiological inhibitor of feeding. |
| 36 | 10334300 | We have examined the effects of underfeeding and obesity on the density of hypothalamic melanocortin MC3 and MC4 receptors (MC3-R and MC4-R, respectively), which may mediate the hypophagic effects of alpha-melanocyte-stimulating hormone (MSH) in the rat. |
| 37 | 10334300 | MC3-R and MC4-R were measured by quantitative autoradiography in brain sections using 125I-labeled Nle4-D-Phe7-alpha-MSH (125I-NDP-MSH) and discriminated by masking MC3-R with excess unlabelled gamma2-MSH. |
| 38 | 10334300 | We suggest that increased density of MC4-R with food restriction and in obese Zucker rats reflects receptor upregulation secondary to decreased release of alpha-MSH, consistent with increased hunger in these models. |
| 39 | 10334300 | Conversely, downregulation of MC4-R in diet-induced obesity may indicate increased alpha-MSH secretion in an attempt to limit overeating. |
| 40 | 10334300 | This alpha-MSH/MC4-R system may be inhibited by leptin and/or insulin. |
| 41 | 10334300 | Altered energy balance causes selective changes in melanocortin-4(MC4-R), but not melanocortin-3 (MC3-R), receptors in specific hypothalamic regions: further evidence that activation of MC4-R is a physiological inhibitor of feeding. |
| 42 | 10334300 | We have examined the effects of underfeeding and obesity on the density of hypothalamic melanocortin MC3 and MC4 receptors (MC3-R and MC4-R, respectively), which may mediate the hypophagic effects of alpha-melanocyte-stimulating hormone (MSH) in the rat. |
| 43 | 10334300 | MC3-R and MC4-R were measured by quantitative autoradiography in brain sections using 125I-labeled Nle4-D-Phe7-alpha-MSH (125I-NDP-MSH) and discriminated by masking MC3-R with excess unlabelled gamma2-MSH. |
| 44 | 10334300 | We suggest that increased density of MC4-R with food restriction and in obese Zucker rats reflects receptor upregulation secondary to decreased release of alpha-MSH, consistent with increased hunger in these models. |
| 45 | 10334300 | Conversely, downregulation of MC4-R in diet-induced obesity may indicate increased alpha-MSH secretion in an attempt to limit overeating. |
| 46 | 10334300 | This alpha-MSH/MC4-R system may be inhibited by leptin and/or insulin. |
| 47 | 10334300 | Altered energy balance causes selective changes in melanocortin-4(MC4-R), but not melanocortin-3 (MC3-R), receptors in specific hypothalamic regions: further evidence that activation of MC4-R is a physiological inhibitor of feeding. |
| 48 | 10334300 | We have examined the effects of underfeeding and obesity on the density of hypothalamic melanocortin MC3 and MC4 receptors (MC3-R and MC4-R, respectively), which may mediate the hypophagic effects of alpha-melanocyte-stimulating hormone (MSH) in the rat. |
| 49 | 10334300 | MC3-R and MC4-R were measured by quantitative autoradiography in brain sections using 125I-labeled Nle4-D-Phe7-alpha-MSH (125I-NDP-MSH) and discriminated by masking MC3-R with excess unlabelled gamma2-MSH. |
| 50 | 10334300 | We suggest that increased density of MC4-R with food restriction and in obese Zucker rats reflects receptor upregulation secondary to decreased release of alpha-MSH, consistent with increased hunger in these models. |
| 51 | 10334300 | Conversely, downregulation of MC4-R in diet-induced obesity may indicate increased alpha-MSH secretion in an attempt to limit overeating. |
| 52 | 10334300 | This alpha-MSH/MC4-R system may be inhibited by leptin and/or insulin. |
| 53 | 10693955 | It is striking that plasma leptin levels at 1 week were inversely correlated with MC4-R density in the VMH, suggesting that this is a key site of leptin action. |
| 54 | 10868932 | We investigated which hypothalamic areas known to express MC4R are involved in the regulation of feeding by using alpha-melanocyte-stimulating hormone (alpha-MSH), an endogenous MC4R agonist, and agouti-related peptide (Agrp), an endogenous MC4R antagonist. |
| 55 | 10868932 | Agrp (83-132) (0.1 nmol) and [Nle4, D-Phe7]alpha(-MSH (NDP-MSH) (0.1 nmol), a stable alpha-MSH analog, were administered to fed and fasted rats, respectively. |
| 56 | 10868932 | The PVN, DMN, and MPO were the areas with the greatest response to Agrp and NDP-MSH. |
| 57 | 10868932 | This study indicates that the hypothalamic nuclei expressing MC4R vary in their sensitivity to Agrp and alpha-MSH with regard to their effect on feeding. |
| 58 | 10868932 | We investigated which hypothalamic areas known to express MC4R are involved in the regulation of feeding by using alpha-melanocyte-stimulating hormone (alpha-MSH), an endogenous MC4R agonist, and agouti-related peptide (Agrp), an endogenous MC4R antagonist. |
| 59 | 10868932 | Agrp (83-132) (0.1 nmol) and [Nle4, D-Phe7]alpha(-MSH (NDP-MSH) (0.1 nmol), a stable alpha-MSH analog, were administered to fed and fasted rats, respectively. |
| 60 | 10868932 | The PVN, DMN, and MPO were the areas with the greatest response to Agrp and NDP-MSH. |
| 61 | 10868932 | This study indicates that the hypothalamic nuclei expressing MC4R vary in their sensitivity to Agrp and alpha-MSH with regard to their effect on feeding. |
| 62 | 10965876 | Furthermore, increased plasma insulin levels occur in the young lean MC4-R knockout (MC4-RKO) mouse, and impaired insulin tolerance takes place before the onset of detectable hyperphagia or obesity. |
| 63 | 11246450 | Decreased function of the melanocortin-4 receptor (MC4R) was reported to cause late-onset obesity and insulin resistance in rodents. |
| 64 | 11272133 | The melanocortin receptor (MC3-R and MC4-R) antagonist, agouti-related protein (AGRP), is a potent stimulant of food intake. |
| 65 | 11272133 | In the AGRP pair-fed group, a significant increase in the epididymal fat pad weight, BAT weight, and plasma leptin was again observed, suggesting that AGRP caused metabolic changes independent of increased food intake. |
| 66 | 11272133 | BAT uncoupling protein 1 (UCP-1) content was significantly decreased compared with saline controls in both the AGRP ad libitum fed (21 +/- 8% of saline control; P < 0.01) and AGRP pair-fed groups (24 +/- 7% of saline control; P < 0.01). |
| 67 | 11272133 | Plasma thyroid-stimulating hormone (TSH) was significantly suppressed compared with saline controls in both the AGRP ad libitum fed and AGRP pair-fed groups (3.5 +/- 0.3 [saline] vs. 2.7 +/- 0.4 [AGRP ad libitum fed] vs. 2.1 +/- 0.2 ng/ml [AGRP pair-fed]; P < 0.01). |
| 68 | 11272133 | This study demonstrates that independent of its orexigenic effects, chronic AGRP treatment decreased BAT UCP-1, suppressed plasma TSH, and increased fat mass and plasma leptin, suggesting that it may play a role in energy expenditure. |
| 69 | 11359864 | AGRP mRNA and neuropeptide Y mRNA were both significantly up-regulated in STZ-DM rats, which are associated with body weight loss, hyperglycemia, hypoinsulinemia and hypoleptinemia. |
| 70 | 11359864 | We proceeded to analyze whether insulin or leptin played the greater role in the regulation of AGRP using Zucker fa/fa rats. |
| 71 | 11359864 | The AGRP mRNA did not differ significantly between fasted fa/fa rats, which have both leptin-insensitivity and hypoinsulinemia, and fed Zuckers, which have leptin-insensitivity and hyperinsulinemia. |
| 72 | 11359864 | We further found that up-regulation of AGRP expression was normalized by infusion of leptin into the third cerebroventricle (i3vt), but not by i3vt infusion of insulin, although up-regulation of AGRP was partially corrected by systemic insulin infusion. |
| 73 | 11359864 | After STZ-DM induction, A(y)/a mice whose melanocortin-4 receptor (MC4-R) was blocked by ectopic expression of agouti protein additionally accelerated hyperphagia and up-regulated AGRP mRNA, implying that the mechanism is triggered by a leptin deficit rather than by the main action of the message through MC4-R. |
| 74 | 11397906 | Likewise, its homologous MC4R in human obesity, MC3R gene is also a good candidate for genetic susceptibility to glucose intolerance and T2DM. |
| 75 | 11756335 | Chronic central melanocortin-4 receptor antagonism and central neuropeptide-Y infusion in rats produce increased adiposity by divergent pathways. |
| 76 | 11756335 | To determine whether similar hormonal and metabolic mechanisms are involved in these two obesity syndromes, we investigated the time course of effects induced by 6-day intracerebroventricular (ICV) infusion of NPY (3.5 nmol/day) or the MC4 receptor antagonist HS014 (4.8 nmol/day) in rats pair-fed with vehicle-infused controls. |
| 77 | 11756335 | Plasma leptin was also increased in both experimental groups (NPY 10.6 +/- 1.9; HS014 4.4 +/- 0.9; control 2.0 +/- 0.1 ng/ml, n = 8-13, P < 0.05 for all comparisons). |
| 78 | 11756335 | Basal plasma corticosterone and insulin levels were increased by ICV NPY infusion, whereas HS014-infused rats showed no significant increase in these parameters on any of 1-6 days of infusion. |
| 79 | 11756335 | Both NPY and HS014 infusion potentiated intravenous glucose-induced (300 mg/kg) plasma insulin levels, and there was no difference in glycemia among groups. |
| 80 | 11756335 | Levels of uncoupling protein-1 mRNA in brown adipose tissue were significantly decreased after 6 days of HS014 infusion, similar to the effect of central NPY. |
| 81 | 11756335 | Because ICV HS014 induced at least as great an increase in fat mass as ICV NPY and yet had divergent hormonal and metabolic effects, we conclude that MC4 receptor antagonism does not induce obesity solely by regulation of the endogenous NPY-ergic system. |
| 82 | 11756335 | Chronic central melanocortin-4 receptor antagonism and central neuropeptide-Y infusion in rats produce increased adiposity by divergent pathways. |
| 83 | 11756335 | To determine whether similar hormonal and metabolic mechanisms are involved in these two obesity syndromes, we investigated the time course of effects induced by 6-day intracerebroventricular (ICV) infusion of NPY (3.5 nmol/day) or the MC4 receptor antagonist HS014 (4.8 nmol/day) in rats pair-fed with vehicle-infused controls. |
| 84 | 11756335 | Plasma leptin was also increased in both experimental groups (NPY 10.6 +/- 1.9; HS014 4.4 +/- 0.9; control 2.0 +/- 0.1 ng/ml, n = 8-13, P < 0.05 for all comparisons). |
| 85 | 11756335 | Basal plasma corticosterone and insulin levels were increased by ICV NPY infusion, whereas HS014-infused rats showed no significant increase in these parameters on any of 1-6 days of infusion. |
| 86 | 11756335 | Both NPY and HS014 infusion potentiated intravenous glucose-induced (300 mg/kg) plasma insulin levels, and there was no difference in glycemia among groups. |
| 87 | 11756335 | Levels of uncoupling protein-1 mRNA in brown adipose tissue were significantly decreased after 6 days of HS014 infusion, similar to the effect of central NPY. |
| 88 | 11756335 | Because ICV HS014 induced at least as great an increase in fat mass as ICV NPY and yet had divergent hormonal and metabolic effects, we conclude that MC4 receptor antagonism does not induce obesity solely by regulation of the endogenous NPY-ergic system. |
| 89 | 11756335 | Chronic central melanocortin-4 receptor antagonism and central neuropeptide-Y infusion in rats produce increased adiposity by divergent pathways. |
| 90 | 11756335 | To determine whether similar hormonal and metabolic mechanisms are involved in these two obesity syndromes, we investigated the time course of effects induced by 6-day intracerebroventricular (ICV) infusion of NPY (3.5 nmol/day) or the MC4 receptor antagonist HS014 (4.8 nmol/day) in rats pair-fed with vehicle-infused controls. |
| 91 | 11756335 | Plasma leptin was also increased in both experimental groups (NPY 10.6 +/- 1.9; HS014 4.4 +/- 0.9; control 2.0 +/- 0.1 ng/ml, n = 8-13, P < 0.05 for all comparisons). |
| 92 | 11756335 | Basal plasma corticosterone and insulin levels were increased by ICV NPY infusion, whereas HS014-infused rats showed no significant increase in these parameters on any of 1-6 days of infusion. |
| 93 | 11756335 | Both NPY and HS014 infusion potentiated intravenous glucose-induced (300 mg/kg) plasma insulin levels, and there was no difference in glycemia among groups. |
| 94 | 11756335 | Levels of uncoupling protein-1 mRNA in brown adipose tissue were significantly decreased after 6 days of HS014 infusion, similar to the effect of central NPY. |
| 95 | 11756335 | Because ICV HS014 induced at least as great an increase in fat mass as ICV NPY and yet had divergent hormonal and metabolic effects, we conclude that MC4 receptor antagonism does not induce obesity solely by regulation of the endogenous NPY-ergic system. |
| 96 | 11756348 | The melanocortin-4 receptor (MC4R) is a member of the seven membrane-spanning G protein-coupled receptor superfamily and signals through the activation of adenylyl cyclase. |
| 97 | 11790431 | This review will discuss this functional diversity by illustrating hypothalamic neurones that express neuropeptide Y (NPY), the melanocortin-4 receptor (MC4-R) and the orexins. |
| 98 | 11790431 | NPY neurones in the arcuate nucleus (ARC) release NPY, a powerful inducer of feeding and obesity, in the paraventricular nucleus (PVN) and the lateral hypothalamic area (LHA). |
| 99 | 11790431 | ARC-NPY neurones are inhibited by leptin and insulin and become overactive when levels of these hormones fall during undernutrition. |
| 100 | 11790431 | With disruption of the inhibitory leptin signals due to gene mutations, the NPY neurones are overactive, which contributes to hyperphagia and obesity in the ob/ob and db/db mice and fa/fa Zucker rat. |
| 101 | 11790431 | The MC4-R is activated by alpha-melanocyte-stimulating hormone [alpha-MSH; a cleavage product of pro-opiomelanocortin (POMC), which is expressed in the other ARC neurones] and inhibits feeding. |
| 102 | 11790431 | Activation of MC4-R, possibly mediated by blockade of AGRP release, appears to restrain overeating of a palatable diet. |
| 103 | 11790431 | Orexin-A and -B (corresponding to hypocretins 1 and 2) are expressed in specific LHA neurones. |
| 104 | 11790431 | Orexin neurones also have close anatomical connections with LHA glucose-sensitive neurones. |
| 105 | 11790431 | This review will discuss this functional diversity by illustrating hypothalamic neurones that express neuropeptide Y (NPY), the melanocortin-4 receptor (MC4-R) and the orexins. |
| 106 | 11790431 | NPY neurones in the arcuate nucleus (ARC) release NPY, a powerful inducer of feeding and obesity, in the paraventricular nucleus (PVN) and the lateral hypothalamic area (LHA). |
| 107 | 11790431 | ARC-NPY neurones are inhibited by leptin and insulin and become overactive when levels of these hormones fall during undernutrition. |
| 108 | 11790431 | With disruption of the inhibitory leptin signals due to gene mutations, the NPY neurones are overactive, which contributes to hyperphagia and obesity in the ob/ob and db/db mice and fa/fa Zucker rat. |
| 109 | 11790431 | The MC4-R is activated by alpha-melanocyte-stimulating hormone [alpha-MSH; a cleavage product of pro-opiomelanocortin (POMC), which is expressed in the other ARC neurones] and inhibits feeding. |
| 110 | 11790431 | Activation of MC4-R, possibly mediated by blockade of AGRP release, appears to restrain overeating of a palatable diet. |
| 111 | 11790431 | Orexin-A and -B (corresponding to hypocretins 1 and 2) are expressed in specific LHA neurones. |
| 112 | 11790431 | Orexin neurones also have close anatomical connections with LHA glucose-sensitive neurones. |
| 113 | 11790431 | This review will discuss this functional diversity by illustrating hypothalamic neurones that express neuropeptide Y (NPY), the melanocortin-4 receptor (MC4-R) and the orexins. |
| 114 | 11790431 | NPY neurones in the arcuate nucleus (ARC) release NPY, a powerful inducer of feeding and obesity, in the paraventricular nucleus (PVN) and the lateral hypothalamic area (LHA). |
| 115 | 11790431 | ARC-NPY neurones are inhibited by leptin and insulin and become overactive when levels of these hormones fall during undernutrition. |
| 116 | 11790431 | With disruption of the inhibitory leptin signals due to gene mutations, the NPY neurones are overactive, which contributes to hyperphagia and obesity in the ob/ob and db/db mice and fa/fa Zucker rat. |
| 117 | 11790431 | The MC4-R is activated by alpha-melanocyte-stimulating hormone [alpha-MSH; a cleavage product of pro-opiomelanocortin (POMC), which is expressed in the other ARC neurones] and inhibits feeding. |
| 118 | 11790431 | Activation of MC4-R, possibly mediated by blockade of AGRP release, appears to restrain overeating of a palatable diet. |
| 119 | 11790431 | Orexin-A and -B (corresponding to hypocretins 1 and 2) are expressed in specific LHA neurones. |
| 120 | 11790431 | Orexin neurones also have close anatomical connections with LHA glucose-sensitive neurones. |
| 121 | 11837451 | Its effect on pigmentation is achieved by antagonizing the binding of alpha-melanocyte stimulating hormone (alpha-MSH) to melanocortin 1 receptor (Mc1r), switching melanin synthesis from eumelanin (black/brown) to phaeomelanin (red/yellow). |
| 122 | 11837451 | The yellow coat colour is the result of agouti chronically antagonizing the binding of alpha-MSH to Mc1r and the obese phenotype results from agouti protein antagonizing the binding of alpha-MSH to Mc3r and/or Mc4r. |
| 123 | 11857934 | [Obesity induced by abnormality in leptin receptor and melanocortin-4 receptor]. |
| 124 | 11857934 | Leptin directly exerts its anorexigenic effects on hypothalamic arcuate nucleus. alpha-melanocyte stimulating hormone (alpha-MSH) derived from proopiomelanocortin (POMC) and melanocortin-4 receptor (MC4-R) have been reported to be involved in the downstream of leptin actions. |
| 125 | 11857934 | In this paper, we summarize the clinical characteristics and the mechanisms of obesity caused by genetic abnormalities in leptin receptor and melanocortin-4 receptor. |
| 126 | 11857934 | [Obesity induced by abnormality in leptin receptor and melanocortin-4 receptor]. |
| 127 | 11857934 | Leptin directly exerts its anorexigenic effects on hypothalamic arcuate nucleus. alpha-melanocyte stimulating hormone (alpha-MSH) derived from proopiomelanocortin (POMC) and melanocortin-4 receptor (MC4-R) have been reported to be involved in the downstream of leptin actions. |
| 128 | 11857934 | In this paper, we summarize the clinical characteristics and the mechanisms of obesity caused by genetic abnormalities in leptin receptor and melanocortin-4 receptor. |
| 129 | 11857934 | [Obesity induced by abnormality in leptin receptor and melanocortin-4 receptor]. |
| 130 | 11857934 | Leptin directly exerts its anorexigenic effects on hypothalamic arcuate nucleus. alpha-melanocyte stimulating hormone (alpha-MSH) derived from proopiomelanocortin (POMC) and melanocortin-4 receptor (MC4-R) have been reported to be involved in the downstream of leptin actions. |
| 131 | 11857934 | In this paper, we summarize the clinical characteristics and the mechanisms of obesity caused by genetic abnormalities in leptin receptor and melanocortin-4 receptor. |
| 132 | 11924926 | In humans, mutations in leptin, leptin receptor, proopiomelanocortin (POMC), melanocortin-4 receptor (MC4R) and prohormone convertase 1 (PC1) have been described in patients with severe obesity. |
| 133 | 11924926 | Most of these obesity disorders, with the exception of the MC4R mutations, exhibit recessive inheritance and a distinct phenotype with varying degrees of hypothalamic dysfunction, and they unravel the critical role of the central leptin and melanocortin pathways in human appetite control and energy homeostasis. |
| 134 | 11924926 | To date, six MODY genes have been identified, the glucokinase gene and five beta cell-specific transcription factor genes, hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-1beta, HNF-4alpha, insulin promoter factor-1 (IPF-1) and NeuroD1/BETA2. |
| 135 | 11924926 | At the other end of the spectrum are the inherited syndromes of insulin resistance that are caused by mutations in the insulin receptor gene and in the adipocyte-specific transcription factor PPARgamma. |
| 136 | 11924926 | In humans, mutations in leptin, leptin receptor, proopiomelanocortin (POMC), melanocortin-4 receptor (MC4R) and prohormone convertase 1 (PC1) have been described in patients with severe obesity. |
| 137 | 11924926 | Most of these obesity disorders, with the exception of the MC4R mutations, exhibit recessive inheritance and a distinct phenotype with varying degrees of hypothalamic dysfunction, and they unravel the critical role of the central leptin and melanocortin pathways in human appetite control and energy homeostasis. |
| 138 | 11924926 | To date, six MODY genes have been identified, the glucokinase gene and five beta cell-specific transcription factor genes, hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-1beta, HNF-4alpha, insulin promoter factor-1 (IPF-1) and NeuroD1/BETA2. |
| 139 | 11924926 | At the other end of the spectrum are the inherited syndromes of insulin resistance that are caused by mutations in the insulin receptor gene and in the adipocyte-specific transcription factor PPARgamma. |
| 140 | 12359499 | The key findings included 1) that the coat color phenotype in the lethal yellow (A(Y)/a) mouse is due to antagonism of the melanocortin-1 receptor (MC1R) by the agouti gene product; 2) the MC3R and MC4R are expressed in CNS centers involved in energy homeostasis, and 3) the combined results of pharmacological studies showing that agouti is an antagonist of the MC4R and transgenic studies showing that inhibition or loss of the MC4R recapitulate the lethal yellow phenotype. |
| 141 | 12359499 | Pro-opiomelanocortin (POMC), MC3R, and MC4R knockouts are obese and are now being used to further analyze melanocortin receptor function. |
| 142 | 12359499 | The obesity phenotype observed in the MC3R and MC4R knockouts (KO) differ markedly. |
| 143 | 12359499 | The key findings included 1) that the coat color phenotype in the lethal yellow (A(Y)/a) mouse is due to antagonism of the melanocortin-1 receptor (MC1R) by the agouti gene product; 2) the MC3R and MC4R are expressed in CNS centers involved in energy homeostasis, and 3) the combined results of pharmacological studies showing that agouti is an antagonist of the MC4R and transgenic studies showing that inhibition or loss of the MC4R recapitulate the lethal yellow phenotype. |
| 144 | 12359499 | Pro-opiomelanocortin (POMC), MC3R, and MC4R knockouts are obese and are now being used to further analyze melanocortin receptor function. |
| 145 | 12359499 | The obesity phenotype observed in the MC3R and MC4R knockouts (KO) differ markedly. |
| 146 | 12359499 | The key findings included 1) that the coat color phenotype in the lethal yellow (A(Y)/a) mouse is due to antagonism of the melanocortin-1 receptor (MC1R) by the agouti gene product; 2) the MC3R and MC4R are expressed in CNS centers involved in energy homeostasis, and 3) the combined results of pharmacological studies showing that agouti is an antagonist of the MC4R and transgenic studies showing that inhibition or loss of the MC4R recapitulate the lethal yellow phenotype. |
| 147 | 12359499 | Pro-opiomelanocortin (POMC), MC3R, and MC4R knockouts are obese and are now being used to further analyze melanocortin receptor function. |
| 148 | 12359499 | The obesity phenotype observed in the MC3R and MC4R knockouts (KO) differ markedly. |
| 149 | 12499395 | A functional analysis of these mutant receptors, in addition to 11 other childhood obesity-associated MC4R mutations, indicates that they all alter the activation of the receptor by the endogenous agonist alpha-MSH. |
| 150 | 12639913 | Preexposure of GT1-7 cells that express endogenous MC4R to the agonist for MC4R, alpha-melanocyte-stimulating hormone, resulted in impaired cAMP formation to a second challenge of alpha-melanocyte-stimulating hormone. |
| 151 | 12639913 | The desensitization of MC4R was accompanied by time-dependent internalization of the receptor in HEK293 cells, which was partly inhibited by pretreatment with a specific protein kinase A (PKA) inhibitor, H89. |
| 152 | 12639913 | Overexpression of dominant-negative mutants of beta-arrestin1-V53D and dynamin I-K44A prevented agonist-mediated internalization of MC4R. |
| 153 | 12639913 | Our data demonstrate that, through PKA-, GRK-, beta-arrestin-, and dynamin-dependent processes, MC4R undergoes internalization in response to agonist, thereby providing novel insights into the regulation of MC4R signaling. |
| 154 | 12639913 | Preexposure of GT1-7 cells that express endogenous MC4R to the agonist for MC4R, alpha-melanocyte-stimulating hormone, resulted in impaired cAMP formation to a second challenge of alpha-melanocyte-stimulating hormone. |
| 155 | 12639913 | The desensitization of MC4R was accompanied by time-dependent internalization of the receptor in HEK293 cells, which was partly inhibited by pretreatment with a specific protein kinase A (PKA) inhibitor, H89. |
| 156 | 12639913 | Overexpression of dominant-negative mutants of beta-arrestin1-V53D and dynamin I-K44A prevented agonist-mediated internalization of MC4R. |
| 157 | 12639913 | Our data demonstrate that, through PKA-, GRK-, beta-arrestin-, and dynamin-dependent processes, MC4R undergoes internalization in response to agonist, thereby providing novel insights into the regulation of MC4R signaling. |
| 158 | 12639913 | Preexposure of GT1-7 cells that express endogenous MC4R to the agonist for MC4R, alpha-melanocyte-stimulating hormone, resulted in impaired cAMP formation to a second challenge of alpha-melanocyte-stimulating hormone. |
| 159 | 12639913 | The desensitization of MC4R was accompanied by time-dependent internalization of the receptor in HEK293 cells, which was partly inhibited by pretreatment with a specific protein kinase A (PKA) inhibitor, H89. |
| 160 | 12639913 | Overexpression of dominant-negative mutants of beta-arrestin1-V53D and dynamin I-K44A prevented agonist-mediated internalization of MC4R. |
| 161 | 12639913 | Our data demonstrate that, through PKA-, GRK-, beta-arrestin-, and dynamin-dependent processes, MC4R undergoes internalization in response to agonist, thereby providing novel insights into the regulation of MC4R signaling. |
| 162 | 12639913 | Preexposure of GT1-7 cells that express endogenous MC4R to the agonist for MC4R, alpha-melanocyte-stimulating hormone, resulted in impaired cAMP formation to a second challenge of alpha-melanocyte-stimulating hormone. |
| 163 | 12639913 | The desensitization of MC4R was accompanied by time-dependent internalization of the receptor in HEK293 cells, which was partly inhibited by pretreatment with a specific protein kinase A (PKA) inhibitor, H89. |
| 164 | 12639913 | Overexpression of dominant-negative mutants of beta-arrestin1-V53D and dynamin I-K44A prevented agonist-mediated internalization of MC4R. |
| 165 | 12639913 | Our data demonstrate that, through PKA-, GRK-, beta-arrestin-, and dynamin-dependent processes, MC4R undergoes internalization in response to agonist, thereby providing novel insights into the regulation of MC4R signaling. |
| 166 | 12851322 | Two melanocortin receptors (MC3R, MC4R) are expressed in brain regions receiving projections of POMC fibers, most of which also receive projections from a population of ARC neurons that co-express neuropeptide Y (NPY) and the MC3R/MC4R antagonist agouti-related peptide (AgRP). |
| 167 | 12851322 | The MC4R, but not the MC3R, is required for the stimulation of energy expenditure in response to melanocortin agonists and voluntary hyperphagia. |
| 168 | 12851322 | Two melanocortin receptors (MC3R, MC4R) are expressed in brain regions receiving projections of POMC fibers, most of which also receive projections from a population of ARC neurons that co-express neuropeptide Y (NPY) and the MC3R/MC4R antagonist agouti-related peptide (AgRP). |
| 169 | 12851322 | The MC4R, but not the MC3R, is required for the stimulation of energy expenditure in response to melanocortin agonists and voluntary hyperphagia. |
| 170 | 12883655 | We investigated if agouti-related peptide (AgRP), an endogenous antagonist of melanocortin receptors (MC3-R and MC4-R), effects energy expenditure in rats. |
| 171 | 12883655 | Despite the absence of hyperphagia and cross-reactivities with MC4-R, AgRP (25-51) and AgRP (54-82) significantly increased body weight and epididymal/mesenteric fat weight. |
| 172 | 12883655 | AgRP (83-132) did not affect glucose and insulin responses to the oral glucose tolerance test. |
| 173 | 12883655 | We investigated if agouti-related peptide (AgRP), an endogenous antagonist of melanocortin receptors (MC3-R and MC4-R), effects energy expenditure in rats. |
| 174 | 12883655 | Despite the absence of hyperphagia and cross-reactivities with MC4-R, AgRP (25-51) and AgRP (54-82) significantly increased body weight and epididymal/mesenteric fat weight. |
| 175 | 12883655 | AgRP (83-132) did not affect glucose and insulin responses to the oral glucose tolerance test. |
| 176 | 14653225 | Leptin activates Arc neurons producing alpha-melanocyte-stimulating hormone (alpha-MSH) and inhibits those producing agouti-related protein (AgRP). alpha-MSH is an endogenous agonist for the melanocortin-4 receptor (MC4-R) that is expressed exclusively in the central nervous system (CNS), whereas AgRP acts as a MC4-R antagonist. |
| 177 | 14693701 | MTII administration for 24 h prevents food deprivation-induced alterations in hypothalamic neuropeptide Y (NPY) and liver adiponectin receptor 1 and adiponectin receptor 2 mRNA expression, but does not alter hypothalamic mRNA expression of melanocortin 4 receptor or adiponectin serum and mRNA expression levels. |
| 178 | 14693701 | NPY and agouti gene-related protein (AgRP) mRNA expression after 8 days of MTII is increased to levels comparable to pair-fed mice. |
| 179 | 14693701 | In summary, 1) MTII is an effective treatment for obesity and related metabolic defects in leptin-resistant (DIO, UCP1-DTA) and leptin-sensitive (ob/ob) mouse models of obesity; 2) the effects of MTII on food intake and body weight are more pronounced in DIO mice than in lean mice; 3) the tachyphylactic effect after prolonged MTII administration appears to be, at least in part, caused by a compensatory upregulation of NPY and AgRP mRNA levels, whereas decreasing leptin levels may play a very minor role in mediating tachyphylaxis; and 4) alterations in adiponectin receptor mRNA expression after fasting or MTII treatment may contribute to altered insulin sensitivity and needs to be studied further. |
| 180 | 15142366 | Leptin was not deficient, and sequencing of the proband's DNA showed no mutations in the perixisome proliferator activated receptor (PPAR)-gamma, PPAR-gamma(2), PPAR-alpha or melanocortin 4 receptor genes. |
| 181 | 16320160 | Alpha melanocyte-stimulating hormone (alpha-MSH) is an agonist at the melanocortin 3 (MC3-R) and melanocortin 4 (MC4-R) receptors. |
| 182 | 16320160 | Agouti related protein (AgRP) is an endogenous antagonist at the MC3-R and MC4-R and is expressed in the rat adrenal cortex. |
| 183 | 16320160 | AgRP antagonises alpha-MSH-induced corticosterone release from rat and bovine adrenal cells. |
| 184 | 16320160 | Alpha melanocyte-stimulating hormone (alpha-MSH) is an agonist at the melanocortin 3 (MC3-R) and melanocortin 4 (MC4-R) receptors. |
| 185 | 16320160 | Agouti related protein (AgRP) is an endogenous antagonist at the MC3-R and MC4-R and is expressed in the rat adrenal cortex. |
| 186 | 16320160 | AgRP antagonises alpha-MSH-induced corticosterone release from rat and bovine adrenal cells. |
| 187 | 16611215 | The Melanocortin-4 Receptor is stimulated by endogenous melanocortin agonists derived from the pro-opiomelanocortin gene transcript and antagonized by the endogenous antagonist agouti-related protein. |
| 188 | 17983585 | We report here that serotonin 2C receptor (5-HT(2C)R) agonists, typically investigated for their anorectic properties, significantly improve glucose tolerance and reduce plasma insulin in murine models of obesity and type 2 diabetes. |
| 189 | 17983585 | We determined that this primary effect on glucose homeostasis requires downstream activation of melanocortin-4 receptors (MC4Rs), but not MC3Rs. |
| 190 | 18454148 | After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. |
| 191 | 18551113 | The aim of this study was to investigate a series of single-nucleotide polymorphisms (SNPs) in the genes MC2R, MC3R, MC4R, MC5R, POMC, and ENPP1 for association with obesity. |
| 192 | 18551113 | Weaker associations were detected between the SNPs rs1541276 in the MC5R, rs1926065 in the MC3R genes and obesity (P = 0.04 and P = 0.03, respectively), and between SNPs rs2236700 in the MC5R, rs2118404 in the POMC, rs943003 in the ENPP1 genes and type 2 diabetes (P = 0.03, P = 0.02 and P = 0.02, respectively); these associations did not, however, remain significant after correction for multiple testing. |
| 193 | 18551113 | In this study, we did not find association between the frequently studied ENPP1 K121Q variant, nor SNPs in the MCR or POMC genes and obesity or type 2 diabetes. |
| 194 | 18551122 | The objectives of this study were to identify potential alterations in gene expression of melanocortin-4 receptor (MC4-R), proopiomelanocortin (POMC), and Agouti-related protein (AgRP) in mouse hypothalamus under a chronic peripheral infusion of leptin or at early (8 weeks) and advanced (16 weeks) phases of diet-induced obesity. |
| 195 | 18551122 | We reported that in control mice, but not in obese mice, leptin infusion induced an increase in POMC mRNA level as well as in MC4-R mRNA level suggesting that leptin could act directly and/or through alpha-melanocyte-stimulating hormone (alpha-MSH). |
| 196 | 18551122 | This hypothesis was reinforced after in vitro studies, using the mouse hypothalamic GT1-7 cell line, since both leptin and Norleucine(4), D-Phenylalanine(7)-alpha-MSH (NDP-alpha-MSH) treatments increased MC4-R expression. |
| 197 | 18551122 | After 8 weeks of high-fat diet, nondiabetic obese mice became resistant to the central action of leptin and their hypothalamic content of POMC and AgRP mRNA were decreased without modification of MC4-R mRNA level. |
| 198 | 18551122 | The objectives of this study were to identify potential alterations in gene expression of melanocortin-4 receptor (MC4-R), proopiomelanocortin (POMC), and Agouti-related protein (AgRP) in mouse hypothalamus under a chronic peripheral infusion of leptin or at early (8 weeks) and advanced (16 weeks) phases of diet-induced obesity. |
| 199 | 18551122 | We reported that in control mice, but not in obese mice, leptin infusion induced an increase in POMC mRNA level as well as in MC4-R mRNA level suggesting that leptin could act directly and/or through alpha-melanocyte-stimulating hormone (alpha-MSH). |
| 200 | 18551122 | This hypothesis was reinforced after in vitro studies, using the mouse hypothalamic GT1-7 cell line, since both leptin and Norleucine(4), D-Phenylalanine(7)-alpha-MSH (NDP-alpha-MSH) treatments increased MC4-R expression. |
| 201 | 18551122 | After 8 weeks of high-fat diet, nondiabetic obese mice became resistant to the central action of leptin and their hypothalamic content of POMC and AgRP mRNA were decreased without modification of MC4-R mRNA level. |
| 202 | 18551122 | The objectives of this study were to identify potential alterations in gene expression of melanocortin-4 receptor (MC4-R), proopiomelanocortin (POMC), and Agouti-related protein (AgRP) in mouse hypothalamus under a chronic peripheral infusion of leptin or at early (8 weeks) and advanced (16 weeks) phases of diet-induced obesity. |
| 203 | 18551122 | We reported that in control mice, but not in obese mice, leptin infusion induced an increase in POMC mRNA level as well as in MC4-R mRNA level suggesting that leptin could act directly and/or through alpha-melanocyte-stimulating hormone (alpha-MSH). |
| 204 | 18551122 | This hypothesis was reinforced after in vitro studies, using the mouse hypothalamic GT1-7 cell line, since both leptin and Norleucine(4), D-Phenylalanine(7)-alpha-MSH (NDP-alpha-MSH) treatments increased MC4-R expression. |
| 205 | 18551122 | After 8 weeks of high-fat diet, nondiabetic obese mice became resistant to the central action of leptin and their hypothalamic content of POMC and AgRP mRNA were decreased without modification of MC4-R mRNA level. |
| 206 | 18551122 | The objectives of this study were to identify potential alterations in gene expression of melanocortin-4 receptor (MC4-R), proopiomelanocortin (POMC), and Agouti-related protein (AgRP) in mouse hypothalamus under a chronic peripheral infusion of leptin or at early (8 weeks) and advanced (16 weeks) phases of diet-induced obesity. |
| 207 | 18551122 | We reported that in control mice, but not in obese mice, leptin infusion induced an increase in POMC mRNA level as well as in MC4-R mRNA level suggesting that leptin could act directly and/or through alpha-melanocyte-stimulating hormone (alpha-MSH). |
| 208 | 18551122 | This hypothesis was reinforced after in vitro studies, using the mouse hypothalamic GT1-7 cell line, since both leptin and Norleucine(4), D-Phenylalanine(7)-alpha-MSH (NDP-alpha-MSH) treatments increased MC4-R expression. |
| 209 | 18551122 | After 8 weeks of high-fat diet, nondiabetic obese mice became resistant to the central action of leptin and their hypothalamic content of POMC and AgRP mRNA were decreased without modification of MC4-R mRNA level. |
| 210 | 18697794 | Recent genome wide scans found common variants near MC4R were related to obesity and insulin resistance. |
| 211 | 19079260 | This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity. |
| 212 | 19091795 | The objectives of this study were to determine if mutations impairing the function of MC4R or MC3R were associated with severe obesity in North American adults. |
| 213 | 19091795 | We studied MC4R and MC3R mutations detected in a total of 1821 adults (889 severely obese and 932 lean controls) from two cohorts. |
| 214 | 19091795 | We systematically and comparatively evaluated the functional consequences of all mutations found in both MC4R and MC3R. |
| 215 | 19091795 | The objectives of this study were to determine if mutations impairing the function of MC4R or MC3R were associated with severe obesity in North American adults. |
| 216 | 19091795 | We studied MC4R and MC3R mutations detected in a total of 1821 adults (889 severely obese and 932 lean controls) from two cohorts. |
| 217 | 19091795 | We systematically and comparatively evaluated the functional consequences of all mutations found in both MC4R and MC3R. |
| 218 | 19091795 | The objectives of this study were to determine if mutations impairing the function of MC4R or MC3R were associated with severe obesity in North American adults. |
| 219 | 19091795 | We studied MC4R and MC3R mutations detected in a total of 1821 adults (889 severely obese and 932 lean controls) from two cohorts. |
| 220 | 19091795 | We systematically and comparatively evaluated the functional consequences of all mutations found in both MC4R and MC3R. |
| 221 | 19164386 | Recent genome-wide association studies (GWAS) have identified multiple risk loci for common obesity (FTO, MC4R, TMEM18, GNPDA2, SH2B1, KCTD15, MTCH2, NEGR1 and PCSK1). |
| 222 | 19255736 | Combined effects of MC4R and FTO common genetic variants on obesity in European general populations. |
| 223 | 19255736 | Compared to participants carrying neither FTO nor MC4R risk allele (20-24% of the populations), subjects with three or four risk alleles (7-10% of the populations) had a 3-fold increased susceptibility of developing obesity during childhood. |
| 224 | 19255736 | Prospectively, we demonstrated that each FTO and MC4R risk allele increased obesity and T2D incidences by 24% (P = 0.02) and 21% (P = 0.02), respectively. |
| 225 | 19255736 | In European general populations, the combined effects of common polymorphisms in FTO and MC4R are therefore additive, predictive of obesity and T2D, and may be influenced by interactions with physical activity levels and gender, respectively. |
| 226 | 19255736 | Combined effects of MC4R and FTO common genetic variants on obesity in European general populations. |
| 227 | 19255736 | Compared to participants carrying neither FTO nor MC4R risk allele (20-24% of the populations), subjects with three or four risk alleles (7-10% of the populations) had a 3-fold increased susceptibility of developing obesity during childhood. |
| 228 | 19255736 | Prospectively, we demonstrated that each FTO and MC4R risk allele increased obesity and T2D incidences by 24% (P = 0.02) and 21% (P = 0.02), respectively. |
| 229 | 19255736 | In European general populations, the combined effects of common polymorphisms in FTO and MC4R are therefore additive, predictive of obesity and T2D, and may be influenced by interactions with physical activity levels and gender, respectively. |
| 230 | 19255736 | Combined effects of MC4R and FTO common genetic variants on obesity in European general populations. |
| 231 | 19255736 | Compared to participants carrying neither FTO nor MC4R risk allele (20-24% of the populations), subjects with three or four risk alleles (7-10% of the populations) had a 3-fold increased susceptibility of developing obesity during childhood. |
| 232 | 19255736 | Prospectively, we demonstrated that each FTO and MC4R risk allele increased obesity and T2D incidences by 24% (P = 0.02) and 21% (P = 0.02), respectively. |
| 233 | 19255736 | In European general populations, the combined effects of common polymorphisms in FTO and MC4R are therefore additive, predictive of obesity and T2D, and may be influenced by interactions with physical activity levels and gender, respectively. |
| 234 | 19255736 | Combined effects of MC4R and FTO common genetic variants on obesity in European general populations. |
| 235 | 19255736 | Compared to participants carrying neither FTO nor MC4R risk allele (20-24% of the populations), subjects with three or four risk alleles (7-10% of the populations) had a 3-fold increased susceptibility of developing obesity during childhood. |
| 236 | 19255736 | Prospectively, we demonstrated that each FTO and MC4R risk allele increased obesity and T2D incidences by 24% (P = 0.02) and 21% (P = 0.02), respectively. |
| 237 | 19255736 | In European general populations, the combined effects of common polymorphisms in FTO and MC4R are therefore additive, predictive of obesity and T2D, and may be influenced by interactions with physical activity levels and gender, respectively. |
| 238 | 19557197 | In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4x10(-7))]. |
| 239 | 19680233 | Recent genome-wide association studies (GWAS) in Asian Indians reported strong associations of variants near melanocortin-4 receptor (MC4R) and MLX interacting protein-like (MLXIPL) genes with insulin resistance and several obesity-related quantitative traits (QTs). |
| 240 | 19680233 | Here, we evaluated the association of two variants (rs12970134 and rs4450508) near MC4R and a nonsynonymous (Gln241His) variant (rs3812316) in MLXIPL gene with type 2 diabetes (T2D) and obesity-related QTs in our case-control cohort (n = 1,528; 745 T2D cases and 783 controls) from a Sikh population from North India. |
| 241 | 19680233 | Recent genome-wide association studies (GWAS) in Asian Indians reported strong associations of variants near melanocortin-4 receptor (MC4R) and MLX interacting protein-like (MLXIPL) genes with insulin resistance and several obesity-related quantitative traits (QTs). |
| 242 | 19680233 | Here, we evaluated the association of two variants (rs12970134 and rs4450508) near MC4R and a nonsynonymous (Gln241His) variant (rs3812316) in MLXIPL gene with type 2 diabetes (T2D) and obesity-related QTs in our case-control cohort (n = 1,528; 745 T2D cases and 783 controls) from a Sikh population from North India. |
| 243 | 19955787 | Candidate gene variants for polygenic obesity appear to disrupt pathways involved in the regulation of energy intake and expenditure and include adrenergic receptors, uncoupling proteins, PPARG, POMC, MC4R and a set of single nucleotide polymorphisms in the FTO locus. |
| 244 | 20215397 | Implication of genetic variants near NEGR1, SEC16B, TMEM18, ETV5/DGKG, GNPDA2, LIN7C/BDNF, MTCH2, BCDIN3D/FAIM2, SH2B1, FTO, MC4R, and KCTD15 with obesity and type 2 diabetes in 7705 Chinese. |
| 245 | 21063808 | Genetic variants of FTO and MC4R have been linked with obesity and T2DM in populations of Europeans. |
| 246 | 21063808 | BMI of participants carrying neither FTO nor MC4R risk allele was 25.9 ± 4.9, one risk allele was 26.4 ± 5.1, two risk alleles was 28.1 ± 5.5, and there or four risk alleles was 33.2 ± 6.3. |
| 247 | 21063808 | We found no association between FTO and MC4R and the Chinese population with T2DM (P > 0.05). |
| 248 | 21063808 | No association between FTO and MC4R and Chinese population with T2DM was found. |
| 249 | 21063808 | Genetic variants of FTO and MC4R have been linked with obesity and T2DM in populations of Europeans. |
| 250 | 21063808 | BMI of participants carrying neither FTO nor MC4R risk allele was 25.9 ± 4.9, one risk allele was 26.4 ± 5.1, two risk alleles was 28.1 ± 5.5, and there or four risk alleles was 33.2 ± 6.3. |
| 251 | 21063808 | We found no association between FTO and MC4R and the Chinese population with T2DM (P > 0.05). |
| 252 | 21063808 | No association between FTO and MC4R and Chinese population with T2DM was found. |
| 253 | 21063808 | Genetic variants of FTO and MC4R have been linked with obesity and T2DM in populations of Europeans. |
| 254 | 21063808 | BMI of participants carrying neither FTO nor MC4R risk allele was 25.9 ± 4.9, one risk allele was 26.4 ± 5.1, two risk alleles was 28.1 ± 5.5, and there or four risk alleles was 33.2 ± 6.3. |
| 255 | 21063808 | We found no association between FTO and MC4R and the Chinese population with T2DM (P > 0.05). |
| 256 | 21063808 | No association between FTO and MC4R and Chinese population with T2DM was found. |
| 257 | 21063808 | Genetic variants of FTO and MC4R have been linked with obesity and T2DM in populations of Europeans. |
| 258 | 21063808 | BMI of participants carrying neither FTO nor MC4R risk allele was 25.9 ± 4.9, one risk allele was 26.4 ± 5.1, two risk alleles was 28.1 ± 5.5, and there or four risk alleles was 33.2 ± 6.3. |
| 259 | 21063808 | We found no association between FTO and MC4R and the Chinese population with T2DM (P > 0.05). |
| 260 | 21063808 | No association between FTO and MC4R and Chinese population with T2DM was found. |
| 261 | 21127480 | While knocking out and phenotypically screening mouse orthologs of thousands of druggable human genes, we found KSR2 knockout (KSR2(-/-)) mice to be more obese and glucose intolerant than melanocortin 4 receptor(-/-) (MC4R(-/-)) mice. |
| 262 | 21127480 | The obesity and T2D of KSR2(-/-) mice resulted from hyperphagia which was unresponsive to leptin and did not originate downstream of MC4R. |
| 263 | 21127480 | The kinases AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) are each linked to food intake regulation, but only mTOR had increased activity in KSR2(-/-) mouse brain, and the ability of rapamycin to inhibit food intake in KSR2(-/-) mice further implicated mTOR in this process. |
| 264 | 21127480 | While knocking out and phenotypically screening mouse orthologs of thousands of druggable human genes, we found KSR2 knockout (KSR2(-/-)) mice to be more obese and glucose intolerant than melanocortin 4 receptor(-/-) (MC4R(-/-)) mice. |
| 265 | 21127480 | The obesity and T2D of KSR2(-/-) mice resulted from hyperphagia which was unresponsive to leptin and did not originate downstream of MC4R. |
| 266 | 21127480 | The kinases AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) are each linked to food intake regulation, but only mTOR had increased activity in KSR2(-/-) mouse brain, and the ability of rapamycin to inhibit food intake in KSR2(-/-) mice further implicated mTOR in this process. |
| 267 | 21209091 | Its disruption causes severe obesity in mice and humans. cAMP-response element-binding protein 1 (CREB1) has been postulated to play an important role downstream of the melanocortin-4 receptor (MC4R), but this hypothesis has never been confirmed in vivo. |
| 268 | 21209091 | To test this, we generated mice that lack CREB1 in SIM1-expressing neurons, of the paraventricular nucleus (PVN), which are known to be MC4R-positive. |
| 269 | 21209091 | Surprisingly, MC4R function tested pharmacologically was normal in CREB1(ΔSIM1) mice, suggesting that CREB1 is not required for intact MC4R signaling. |
| 270 | 21209091 | Its disruption causes severe obesity in mice and humans. cAMP-response element-binding protein 1 (CREB1) has been postulated to play an important role downstream of the melanocortin-4 receptor (MC4R), but this hypothesis has never been confirmed in vivo. |
| 271 | 21209091 | To test this, we generated mice that lack CREB1 in SIM1-expressing neurons, of the paraventricular nucleus (PVN), which are known to be MC4R-positive. |
| 272 | 21209091 | Surprisingly, MC4R function tested pharmacologically was normal in CREB1(ΔSIM1) mice, suggesting that CREB1 is not required for intact MC4R signaling. |
| 273 | 21209091 | Its disruption causes severe obesity in mice and humans. cAMP-response element-binding protein 1 (CREB1) has been postulated to play an important role downstream of the melanocortin-4 receptor (MC4R), but this hypothesis has never been confirmed in vivo. |
| 274 | 21209091 | To test this, we generated mice that lack CREB1 in SIM1-expressing neurons, of the paraventricular nucleus (PVN), which are known to be MC4R-positive. |
| 275 | 21209091 | Surprisingly, MC4R function tested pharmacologically was normal in CREB1(ΔSIM1) mice, suggesting that CREB1 is not required for intact MC4R signaling. |
| 276 | 21283731 | FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome. |
| 277 | 21460229 | Mahogany (Attractin, Atrn/mg) and mahoganoid (Mahogunin Ring Finger-1, Mgrn1/md) are mutations epistatic to A(y). |
| 278 | 21460229 | These mutations have been described as suppressors of ASP action, blocking its antagonizing effects on the melanocortin 1 and 4 receptors (MC1R and MC4R) in the skin and the brain, respectively, via unknown mechanisms. |
| 279 | 21460229 | We show that overexpression of ASP inhibits the rise in cAMP levels in response to α-melanocyte-stimulating hormone, an MC4R agonist, by blocking ligand binding and by directing MC4R trafficking to the lysosome. |
| 280 | 21460229 | Loss-of-function of either attractin or MGRN1 blocks ASP-dependent MC4R degradation and promotes increased trafficking of internalized MC4R to the cell surface, but it does not restore α-melanocyte-stimulating hormone-dependent cAMP signaling. |
| 281 | 21460229 | We propose that MGRN1 and attractin are components of an evolutionarily conserved receptor trafficking pathway and that the md and mg mutations rescue the A(y) phenotypes by a primarily cAMP-independent mechanism promoting trafficking of MC4R and likely MC1R away from the lysosome toward the cell surface. |
| 282 | 21460229 | Mahogany (Attractin, Atrn/mg) and mahoganoid (Mahogunin Ring Finger-1, Mgrn1/md) are mutations epistatic to A(y). |
| 283 | 21460229 | These mutations have been described as suppressors of ASP action, blocking its antagonizing effects on the melanocortin 1 and 4 receptors (MC1R and MC4R) in the skin and the brain, respectively, via unknown mechanisms. |
| 284 | 21460229 | We show that overexpression of ASP inhibits the rise in cAMP levels in response to α-melanocyte-stimulating hormone, an MC4R agonist, by blocking ligand binding and by directing MC4R trafficking to the lysosome. |
| 285 | 21460229 | Loss-of-function of either attractin or MGRN1 blocks ASP-dependent MC4R degradation and promotes increased trafficking of internalized MC4R to the cell surface, but it does not restore α-melanocyte-stimulating hormone-dependent cAMP signaling. |
| 286 | 21460229 | We propose that MGRN1 and attractin are components of an evolutionarily conserved receptor trafficking pathway and that the md and mg mutations rescue the A(y) phenotypes by a primarily cAMP-independent mechanism promoting trafficking of MC4R and likely MC1R away from the lysosome toward the cell surface. |
| 287 | 21460229 | Mahogany (Attractin, Atrn/mg) and mahoganoid (Mahogunin Ring Finger-1, Mgrn1/md) are mutations epistatic to A(y). |
| 288 | 21460229 | These mutations have been described as suppressors of ASP action, blocking its antagonizing effects on the melanocortin 1 and 4 receptors (MC1R and MC4R) in the skin and the brain, respectively, via unknown mechanisms. |
| 289 | 21460229 | We show that overexpression of ASP inhibits the rise in cAMP levels in response to α-melanocyte-stimulating hormone, an MC4R agonist, by blocking ligand binding and by directing MC4R trafficking to the lysosome. |
| 290 | 21460229 | Loss-of-function of either attractin or MGRN1 blocks ASP-dependent MC4R degradation and promotes increased trafficking of internalized MC4R to the cell surface, but it does not restore α-melanocyte-stimulating hormone-dependent cAMP signaling. |
| 291 | 21460229 | We propose that MGRN1 and attractin are components of an evolutionarily conserved receptor trafficking pathway and that the md and mg mutations rescue the A(y) phenotypes by a primarily cAMP-independent mechanism promoting trafficking of MC4R and likely MC1R away from the lysosome toward the cell surface. |
| 292 | 21460229 | Mahogany (Attractin, Atrn/mg) and mahoganoid (Mahogunin Ring Finger-1, Mgrn1/md) are mutations epistatic to A(y). |
| 293 | 21460229 | These mutations have been described as suppressors of ASP action, blocking its antagonizing effects on the melanocortin 1 and 4 receptors (MC1R and MC4R) in the skin and the brain, respectively, via unknown mechanisms. |
| 294 | 21460229 | We show that overexpression of ASP inhibits the rise in cAMP levels in response to α-melanocyte-stimulating hormone, an MC4R agonist, by blocking ligand binding and by directing MC4R trafficking to the lysosome. |
| 295 | 21460229 | Loss-of-function of either attractin or MGRN1 blocks ASP-dependent MC4R degradation and promotes increased trafficking of internalized MC4R to the cell surface, but it does not restore α-melanocyte-stimulating hormone-dependent cAMP signaling. |
| 296 | 21460229 | We propose that MGRN1 and attractin are components of an evolutionarily conserved receptor trafficking pathway and that the md and mg mutations rescue the A(y) phenotypes by a primarily cAMP-independent mechanism promoting trafficking of MC4R and likely MC1R away from the lysosome toward the cell surface. |
| 297 | 21710454 | Mutations in the melanocortin-4 receptor (MC4R) are associated with severe obesity, independent of their effect on cortisol or thyroid-stimulating hormone levels. |
| 298 | 21710454 | We examined a morbidly obese male (BMI = 62 kg/m²) with a binge-eating disorder and eight family members for mutations in the MC4R gene and potential differences in leptin levels. |
| 299 | 21710454 | Mutations in the melanocortin-4 receptor (MC4R) are associated with severe obesity, independent of their effect on cortisol or thyroid-stimulating hormone levels. |
| 300 | 21710454 | We examined a morbidly obese male (BMI = 62 kg/m²) with a binge-eating disorder and eight family members for mutations in the MC4R gene and potential differences in leptin levels. |
| 301 | 21796137 | Association of variations in the FTO, SCG3 and MTMR9 genes with metabolic syndrome in a Japanese population. |
| 302 | 21796137 | There is evidence that obesity and obesity-related phenotypes are associated with variations in several genes, including NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, SH2B1, FTO, MAF, MC4R, KCTD15, SCG3, MTMR9, TFAP2B, MSRA, LYPLAL1, GCKR and FADS1. |
| 303 | 21796137 | Four SNPs in the FTO gene were significantly related to metabolic syndrome: rs9939609 (P=0.00013), rs8050136 (P=0.00011), rs1558902 (P=6.6 × 10(-5)) and rs1421085 (P=7.4 × 10(-5)). rs3764220 in the SCG3 gene (P=0.0010) and rs2293855 in the MTMR9 gene (P=0.0015) were also significantly associated with metabolic syndrome. |
| 304 | 21796137 | SNPs in the FTO, SCG3 and MTMR9 genes had no SNP × SNP epistatic effects on metabolic syndrome. |
| 305 | 21796137 | Our data suggest that genetic variations in the FTO, SCG3 and MTMR9 genes independently influence the risk of metabolic syndrome. |
| 306 | 21865462 | Peripheral Melotan II (MTII) injection increased iBAT temperature, but it was blunted by blockade of DMH melanocortin receptors (MC4Rs) by injecting agouti-related peptide (AgRP) directly into the DMH, suggesting a physiological role of the DMH on temperature regulation in animals with normal body weight. |
| 307 | 21865462 | Nevertheless, obese mice without a functional melanocortin system (MC4R KO mice) have an increased sympathetic outflow to iBAT compared with their littermates, suggesting that higher leptin levels drive sympathoexcitation to iBAT by a melanocortin-independent pathway. |
| 308 | 21865462 | Peripheral Melotan II (MTII) injection increased iBAT temperature, but it was blunted by blockade of DMH melanocortin receptors (MC4Rs) by injecting agouti-related peptide (AgRP) directly into the DMH, suggesting a physiological role of the DMH on temperature regulation in animals with normal body weight. |
| 309 | 21865462 | Nevertheless, obese mice without a functional melanocortin system (MC4R KO mice) have an increased sympathetic outflow to iBAT compared with their littermates, suggesting that higher leptin levels drive sympathoexcitation to iBAT by a melanocortin-independent pathway. |
| 310 | 21894153 | The HTR2C and leptin genes are among the most promising, and new evidence suggests that the DRD2, TNF, SNAP-25 and MC4R genes are also prominent risk factors. |
| 311 | 21894153 | Further promising findings have been reported in novel susceptibility genes, such as CNR1, MDR1, ADRA1A and INSIG2. |
| 312 | 21921652 | Evaluation of the obesity genes FTO and MC4R and the type 2 diabetes mellitus gene TCF7L2 for contribution to stroke risk: The Mannheim-Heidelberg Stroke Study. |
| 313 | 22041983 | Eight loci, rs10968576 (BDNF), rs3817334 (MTCH2), rs1558902 (FTO), rs571312 (MC4R), rs543874 (SEC16B), rs987237 (TFAP2B), rs2867125 (TMEM18) and rs7138803 (FAIM2), were previously known obesity susceptibility loci, and the remaining four loci, rs1514175 (TNNI3K), rs206936 (NUDT3), rs4771122 (MTIF3) and rs2241423 (MAP2K5), were newly identified as BMI loci by the GIANT study. |
| 314 | 22043166 | In particular, the specific genes that will be presented (FTO, MC4R, and NPC1) have recently been associated with childhood obesity through a genome-wide association study (GWAS) and were shown to interact with nutritional components to increase weight gain. |
| 315 | 22100407 | NPY and MC4R signaling regulate thyroid hormone levels during fasting through both central and peripheral pathways. |
| 316 | 22100407 | Previous studies demonstrate that leptin communicates nutritional status to the HPT axis through thyrotropin-releasing hormone (TRH) in the paraventricular nucleus (PVN) of the hypothalamus. |
| 317 | 22100407 | Leptin targets TRH neurons either directly or indirectly via the arcuate nucleus through pro-opiomelanocortin (POMC) and agouti-related peptide/neuropeptide Y (AgRP/NPY) neurons. |
| 318 | 22100407 | To evaluate the role of these pathways in vivo, we developed double knockout mice that lack both the melanocortin 4 receptor (MC4R) and NPY. |
| 319 | 22100407 | We show that NPY is required for fasting-induced suppression of Trh expression in the PVN. |
| 320 | 22100407 | However, both MC4R and NPY are required for activation of hepatic pathways that metabolize T(4) during the fasting response. |
| 321 | 22100407 | NPY and MC4R signaling regulate thyroid hormone levels during fasting through both central and peripheral pathways. |
| 322 | 22100407 | Previous studies demonstrate that leptin communicates nutritional status to the HPT axis through thyrotropin-releasing hormone (TRH) in the paraventricular nucleus (PVN) of the hypothalamus. |
| 323 | 22100407 | Leptin targets TRH neurons either directly or indirectly via the arcuate nucleus through pro-opiomelanocortin (POMC) and agouti-related peptide/neuropeptide Y (AgRP/NPY) neurons. |
| 324 | 22100407 | To evaluate the role of these pathways in vivo, we developed double knockout mice that lack both the melanocortin 4 receptor (MC4R) and NPY. |
| 325 | 22100407 | We show that NPY is required for fasting-induced suppression of Trh expression in the PVN. |
| 326 | 22100407 | However, both MC4R and NPY are required for activation of hepatic pathways that metabolize T(4) during the fasting response. |
| 327 | 22100407 | NPY and MC4R signaling regulate thyroid hormone levels during fasting through both central and peripheral pathways. |
| 328 | 22100407 | Previous studies demonstrate that leptin communicates nutritional status to the HPT axis through thyrotropin-releasing hormone (TRH) in the paraventricular nucleus (PVN) of the hypothalamus. |
| 329 | 22100407 | Leptin targets TRH neurons either directly or indirectly via the arcuate nucleus through pro-opiomelanocortin (POMC) and agouti-related peptide/neuropeptide Y (AgRP/NPY) neurons. |
| 330 | 22100407 | To evaluate the role of these pathways in vivo, we developed double knockout mice that lack both the melanocortin 4 receptor (MC4R) and NPY. |
| 331 | 22100407 | We show that NPY is required for fasting-induced suppression of Trh expression in the PVN. |
| 332 | 22100407 | However, both MC4R and NPY are required for activation of hepatic pathways that metabolize T(4) during the fasting response. |
| 333 | 22272442 | Influence of obesity-susceptibility loci (MC4R and INSIG2) on the outcome of weight loss and amelioration of co-morbidity in obese patients treated by a gastric-bypass. |
| 334 | 22466342 | β2-adrenergic receptor Thr164Ile polymorphism, obesity, and diabetes: comparison with FTO, MC4R, and TMEM18 polymorphisms in more than 64,000 individuals. |
| 335 | 22787141 | S6K1 in the central nervous system regulates energy expenditure via MC4R/CRH pathways in response to deprivation of an essential amino acid. |
| 336 | 22787141 | Furthermore, we show that the effect of hypothalamic S6K1 is mediated by modulation of Crh expression in a melanocortin-4 receptor-dependent manner. |
| 337 | 22787141 | S6K1 in the central nervous system regulates energy expenditure via MC4R/CRH pathways in response to deprivation of an essential amino acid. |
| 338 | 22787141 | Furthermore, we show that the effect of hypothalamic S6K1 is mediated by modulation of Crh expression in a melanocortin-4 receptor-dependent manner. |
| 339 | 23680515 | Two neural melanocortin receptors, melanocortin 3 and 4 receptors (MC3R and MC4R), play crucial roles in the regulation of energy balance. |
| 340 | 23727064 | Association of POL1, MALT1, MC4R, PHLPP and DSEL single nucleotide polymorphisms in chromosome 18q region with type 2 diabetes in Tunisians. |
| 341 | 23817596 | The aim of our study is to estimate the prevalence of MS (according to Cook's criteria) in a Chilean cross-sectional sample of 259 obese children (47.1% girls, aged 6-12 years), and to assess the association between common genetic variants of leptin-melanocortin pathway genes (LEP, LEPR, POMC, MC3R and MC4R) with components of the MS using logistic regression. |
| 342 | 23838847 | The mRNA expression of lipid and glucose metabolism genes was changed upon the treatment of human primary adipocytes with SPIONs. mRNA of GULP1, SLC30A8, NEGR1, SEC16B, MTCH2, MAF, MC4R, and TMEM195 were severely induced, whereas INSIG2, NAMPT, MTMR9, PFKP, KCTD15, LPL and GNPDA2 were down-regulated upon SPIONs stimulation. |
| 343 | 23890480 | We performed a study of eleven variants in/near genes TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, and FTO in Czech adolescents and analysed their association with obesity, metabolic syndrome and related traits. |
| 344 | 23890480 | Moreover, MC4R and BDNF variants increased the risk of metabolic syndrome, probably through their effect on abdominal obesity. |
| 345 | 23890480 | We performed a study of eleven variants in/near genes TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, and FTO in Czech adolescents and analysed their association with obesity, metabolic syndrome and related traits. |
| 346 | 23890480 | Moreover, MC4R and BDNF variants increased the risk of metabolic syndrome, probably through their effect on abdominal obesity. |