Ignet

Gene Information

Gene symbol: ACACB

Gene name: acetyl-CoA carboxylase beta

HGNC ID: 85

Synonyms: HACC275, ACC2, ACCB

Related Genes

#	Gene Symbol	Number of hits
1	ACACA	1 hits
2	AKT1	1 hits
3	ATIC	1 hits
4	BCL2A1	1 hits
5	BDNF	1 hits
6	CPT1A	1 hits
7	CRP	1 hits
8	DPP4	1 hits
9	FASN	1 hits
10	GLP1R	1 hits
11	IKBKB	1 hits
12	INS	1 hits
13	LPL	1 hits
14	PPP2R4	1 hits
15	PRKAA1	1 hits
16	PRKAA2	1 hits
17	STK11	1 hits

Related Sentences

#	PMID	Sentence
1	9148944	After 5 min of contraction, ACC-beta activity was decreased by 90% despite an apparent increase in the cytosolic concentration of citrate, a positive regulator of ACC.
2	9148944	In addition, homogenization of the muscles in a buffer free of phosphatase inhibitors and containing the phosphatase activators glutamate and MgCl2 or treatment of immunoprecipitated ACC-beta with purified protein phosphatase 2A abolished the decreases in both ACC-beta activity and electrophoretic mobility caused by contraction.
3	9148944	The rapid decrease in ACC-beta activity after the onset of contractions (50% by 20 s) and its slow restoration to initial values during recovery (60-90 min) were paralleled temporally by reciprocal changes in the activity of the alpha2 but not the alpha1 isoform of 5'-AMP-activated protein kinase (AMPK).
4	9148944	These alterations in ACC and AMPK activity, by diminishing the concentration of malonyl-CoA, could be responsible for the increase in fatty acid oxidation observed in skeletal muscle during exercise.
5	9148944	After 5 min of contraction, ACC-beta activity was decreased by 90% despite an apparent increase in the cytosolic concentration of citrate, a positive regulator of ACC.
6	9148944	In addition, homogenization of the muscles in a buffer free of phosphatase inhibitors and containing the phosphatase activators glutamate and MgCl2 or treatment of immunoprecipitated ACC-beta with purified protein phosphatase 2A abolished the decreases in both ACC-beta activity and electrophoretic mobility caused by contraction.
7	9148944	The rapid decrease in ACC-beta activity after the onset of contractions (50% by 20 s) and its slow restoration to initial values during recovery (60-90 min) were paralleled temporally by reciprocal changes in the activity of the alpha2 but not the alpha1 isoform of 5'-AMP-activated protein kinase (AMPK).
8	9148944	These alterations in ACC and AMPK activity, by diminishing the concentration of malonyl-CoA, could be responsible for the increase in fatty acid oxidation observed in skeletal muscle during exercise.
9	9148944	After 5 min of contraction, ACC-beta activity was decreased by 90% despite an apparent increase in the cytosolic concentration of citrate, a positive regulator of ACC.
10	9148944	In addition, homogenization of the muscles in a buffer free of phosphatase inhibitors and containing the phosphatase activators glutamate and MgCl2 or treatment of immunoprecipitated ACC-beta with purified protein phosphatase 2A abolished the decreases in both ACC-beta activity and electrophoretic mobility caused by contraction.
11	9148944	The rapid decrease in ACC-beta activity after the onset of contractions (50% by 20 s) and its slow restoration to initial values during recovery (60-90 min) were paralleled temporally by reciprocal changes in the activity of the alpha2 but not the alpha1 isoform of 5'-AMP-activated protein kinase (AMPK).
12	9148944	These alterations in ACC and AMPK activity, by diminishing the concentration of malonyl-CoA, could be responsible for the increase in fatty acid oxidation observed in skeletal muscle during exercise.
13	9886945	Conversely, during exercise, when the need of the muscle cell for fatty acid oxidation is increased, decreases in the ATP/AMP and/or creatine phosphate-to-creatine ratios activate an isoform of an AMP-activated protein kinase (AMPK), which phosphorylates ACCbeta and inhibits both its basal activity and activation by citrate.
14	12079837	Leptin has recently been shown to enhance peripheral insulin sensitivity by decreasing the tissue triglyceride accumulation, possibly through regulation of fatty acid oxidation and lipogenesis.
15	12079837	Thus, to test the hypothesis that insulin resistance and increased skeletal muscle lipid accumulation in hHTg rats are due to a defect in lipid catabolism, we measured mitochondrial and peroxisomal fatty acid oxidation and malonyl-CoA and acetyl-CoA carboxylase-2 content in skeletal muscles of these animals.
16	12079837	We found the following: (1) in spite of a higher skeletal muscle malonyl-CoA content and an increased sensitivity of carnitine palmitoyltransferase-1 to malonyl-CoA, carnitine palmitoyltransferase-1 activity in muscle of hHTg rats was normal; (2) increased peroxisomal fatty acid oxidation did not seem to be sufficient to prevent the tissue lipid accumulation in these animals; (3) both lower leptin production by white adipose tissue and increased leptin uptake seem to be responsible for lower circulating leptin levels and therefore lower fatty acid catabolism.
17	12086935	Metformin treatment for 10 weeks significantly increased AMPK alpha2 activity in the skeletal muscle, and this was associated with increased phosphorylation of AMPK on Thr172 and decreased acetyl-CoA carboxylase-2 activity.
18	12086953	Acetyl-CoA carboxylase-2 mRNA expression was significantly decreased after training (P = 0.005), whereas lipoprotein lipase mRNA expression tended to increase (P = 0.07).
19	12393301	This article reviews recent developments in research on several of these targets, namely acetyl-CoA carboxylase 2 (ACC2), I kappa kinase (IKK) beta, dipeptidyl peptidase IV (DPP-IV) and glucagon-like peptide-1 receptor (GLP-1R).
20	12920182	Malonyl-CoA, generated by acetyl-CoA carboxylases ACC1 and ACC2, is a key metabolite in the control of fatty acid synthesis and oxidation in response to dietary changes.
21	12920182	ACC2 is associated to the mitochondria, and Acc2-/- mice have a normal lifespan and higher fatty acid oxidation rate and accumulate less fat.
22	12920182	Fatty acid oxidation rates in the soleus muscle and in hepatocytes of Acc2-/- mice were significantly higher than those of WT cohorts and were not affected by the addition of insulin. mRNA levels of uncoupling proteins (UCPs) were significantly higher in adipose, heart (UCP2), and muscle (UCP3) tissues of mutant mice compared with those of the WT.
23	12920182	Lowering intracellular fatty acid accumulation in the mutant relative to that of the WT mice may thus impact glucose transport by higher GLUT4 activity and insulin sensitivity.
24	12920182	These results suggest that ACC2 plays an essential role in controlling fatty acid oxidation and is a potential target in therapy against obesity and related diseases.
25	12920182	Malonyl-CoA, generated by acetyl-CoA carboxylases ACC1 and ACC2, is a key metabolite in the control of fatty acid synthesis and oxidation in response to dietary changes.
26	12920182	ACC2 is associated to the mitochondria, and Acc2-/- mice have a normal lifespan and higher fatty acid oxidation rate and accumulate less fat.
27	12920182	Fatty acid oxidation rates in the soleus muscle and in hepatocytes of Acc2-/- mice were significantly higher than those of WT cohorts and were not affected by the addition of insulin. mRNA levels of uncoupling proteins (UCPs) were significantly higher in adipose, heart (UCP2), and muscle (UCP3) tissues of mutant mice compared with those of the WT.
28	12920182	Lowering intracellular fatty acid accumulation in the mutant relative to that of the WT mice may thus impact glucose transport by higher GLUT4 activity and insulin sensitivity.
29	12920182	These results suggest that ACC2 plays an essential role in controlling fatty acid oxidation and is a potential target in therapy against obesity and related diseases.
30	12920182	Malonyl-CoA, generated by acetyl-CoA carboxylases ACC1 and ACC2, is a key metabolite in the control of fatty acid synthesis and oxidation in response to dietary changes.
31	12920182	ACC2 is associated to the mitochondria, and Acc2-/- mice have a normal lifespan and higher fatty acid oxidation rate and accumulate less fat.
32	12920182	Fatty acid oxidation rates in the soleus muscle and in hepatocytes of Acc2-/- mice were significantly higher than those of WT cohorts and were not affected by the addition of insulin. mRNA levels of uncoupling proteins (UCPs) were significantly higher in adipose, heart (UCP2), and muscle (UCP3) tissues of mutant mice compared with those of the WT.
33	12920182	Lowering intracellular fatty acid accumulation in the mutant relative to that of the WT mice may thus impact glucose transport by higher GLUT4 activity and insulin sensitivity.
34	12920182	These results suggest that ACC2 plays an essential role in controlling fatty acid oxidation and is a potential target in therapy against obesity and related diseases.
35	14532170	Acute or chronic activation of AMP-activated protein kinase (AMPK) increases insulin sensitivity.
36	14532170	Conversely, reduced expression and/or function of AMPK might play a role in insulin resistance in type 2 diabetes.
37	14532170	Thus protein expression of the seven subunit isoforms of AMPK and activities and/or phosphorylation of AMPK and acetyl-CoA carboxylase-beta (ACCbeta) was measured in skeletal muscle from obese type 2 diabetic and well-matched control subjects during euglycemic-hyperinsulinemic clamps.
38	14532170	Protein expression of all AMPK subunit isoforms (alpha1, alpha2, beta1, beta2, gamma1, gamma2, and gamma3) in muscle of obese type 2 diabetic subjects was similar to that of control subjects.
39	14532170	In addition, alpha1- and alpha2-associated activities of AMPK, phosphorylation of alpha-AMPK subunits at Thr172, and phosphorylation of ACCbeta at Ser221 showed no difference between the two groups and were not regulated by physiological concentrations of insulin.
40	14532170	These data suggest that impaired insulin action on glycogen synthesis and lipid oxidation in skeletal muscle of obese type 2 diabetic subjects is unlikely to involve changes in AMPK expression and activity.
41	14532170	Acute or chronic activation of AMP-activated protein kinase (AMPK) increases insulin sensitivity.
42	14532170	Conversely, reduced expression and/or function of AMPK might play a role in insulin resistance in type 2 diabetes.
43	14532170	Thus protein expression of the seven subunit isoforms of AMPK and activities and/or phosphorylation of AMPK and acetyl-CoA carboxylase-beta (ACCbeta) was measured in skeletal muscle from obese type 2 diabetic and well-matched control subjects during euglycemic-hyperinsulinemic clamps.
44	14532170	Protein expression of all AMPK subunit isoforms (alpha1, alpha2, beta1, beta2, gamma1, gamma2, and gamma3) in muscle of obese type 2 diabetic subjects was similar to that of control subjects.
45	14532170	In addition, alpha1- and alpha2-associated activities of AMPK, phosphorylation of alpha-AMPK subunits at Thr172, and phosphorylation of ACCbeta at Ser221 showed no difference between the two groups and were not regulated by physiological concentrations of insulin.
46	14532170	These data suggest that impaired insulin action on glycogen synthesis and lipid oxidation in skeletal muscle of obese type 2 diabetic subjects is unlikely to involve changes in AMPK expression and activity.
47	15039461	We previously reported that sterol-regulatory-element-binding-protein-1c (SREBP-1c) mediates insulin upregulation of genes encoding glycolytic and lipogenic enzymes in rat skeletal muscle.
48	15039461	Time-course experiments showed that, within 3 hours, glucose stimulated the expression of hexokinase II, fatty acid synthase and acetyl-CoA-carboxylase-2 proteins, leading to an increased lipogenic flux and intracellular lipid accumulation in contracting myotubes.
49	15083594	ACC exists as two tissue-specific isozymes, ACC1 present in lipogenic tissues (liver and adipose) and ACC2 present in oxidative tissues (liver, heart and skeletal muscle).
50	15083594	Studies in both ACC2 knockout mice and animals administered isozyme-nonselective ACC inhibitors have demonstrated the utility of treating metabolic syndrome through this modality.
51	15083594	ACC exists as two tissue-specific isozymes, ACC1 present in lipogenic tissues (liver and adipose) and ACC2 present in oxidative tissues (liver, heart and skeletal muscle).
52	15083594	Studies in both ACC2 knockout mice and animals administered isozyme-nonselective ACC inhibitors have demonstrated the utility of treating metabolic syndrome through this modality.
53	15356065	Obesity in humans is associated with lipid accumulation in skeletal muscle, insulin and leptin resistance, and type 2 diabetes.
54	15356065	To address the hypothesis that lipid accumulation in skeletal muscle of obese subjects may be due to down-regulation of AMPK, we measured mRNA and protein levels of AMPK isoforms, AMPKalpha1 and -alpha2 activity, AMPK kinase activity, acetyl-coenzyme A carboxylase (ACCbeta) expression and phosphorylation, and FA metabolism in biopsies of rectus abdominus muscle from lean and obese women.
55	15356065	We also examined the effect of 5-aminoimidazole-4-carboxamide riboside (AICAR) on AMPK activity and the effects of AICAR and leptin on FA metabolism.
56	15356065	However, AMPK mRNA and protein expression, AMPKalpha1 and -alpha2 activities, AMPK kinase activity, ACCbeta phosphorylation, and FA oxidation were similar in lean and obese subjects.
57	15356065	Moreover, AICAR increased AMPKalpha2 activity, ACCbeta phosphorylation, and palmitate oxidation to a similar degree in muscle from lean and obese subjects.
58	15356065	We conclude that the abnormal lipid metabolism and leptin resistance of skeletal muscle of obese subjects is not due to down-regulation of AMPK.
59	15356065	In addition, the similar stimulation by AICAR of AMPK in skeletal muscle of lean and obese subjects suggests that direct pharmacological activation of AMPK may be a therapeutic approach for stimulating FA oxidation in the treatment of human obesity.
60	15356065	Obesity in humans is associated with lipid accumulation in skeletal muscle, insulin and leptin resistance, and type 2 diabetes.
61	15356065	To address the hypothesis that lipid accumulation in skeletal muscle of obese subjects may be due to down-regulation of AMPK, we measured mRNA and protein levels of AMPK isoforms, AMPKalpha1 and -alpha2 activity, AMPK kinase activity, acetyl-coenzyme A carboxylase (ACCbeta) expression and phosphorylation, and FA metabolism in biopsies of rectus abdominus muscle from lean and obese women.
62	15356065	We also examined the effect of 5-aminoimidazole-4-carboxamide riboside (AICAR) on AMPK activity and the effects of AICAR and leptin on FA metabolism.
63	15356065	However, AMPK mRNA and protein expression, AMPKalpha1 and -alpha2 activities, AMPK kinase activity, ACCbeta phosphorylation, and FA oxidation were similar in lean and obese subjects.
64	15356065	Moreover, AICAR increased AMPKalpha2 activity, ACCbeta phosphorylation, and palmitate oxidation to a similar degree in muscle from lean and obese subjects.
65	15356065	We conclude that the abnormal lipid metabolism and leptin resistance of skeletal muscle of obese subjects is not due to down-regulation of AMPK.
66	15356065	In addition, the similar stimulation by AICAR of AMPK in skeletal muscle of lean and obese subjects suggests that direct pharmacological activation of AMPK may be a therapeutic approach for stimulating FA oxidation in the treatment of human obesity.
67	15356065	Obesity in humans is associated with lipid accumulation in skeletal muscle, insulin and leptin resistance, and type 2 diabetes.
68	15356065	To address the hypothesis that lipid accumulation in skeletal muscle of obese subjects may be due to down-regulation of AMPK, we measured mRNA and protein levels of AMPK isoforms, AMPKalpha1 and -alpha2 activity, AMPK kinase activity, acetyl-coenzyme A carboxylase (ACCbeta) expression and phosphorylation, and FA metabolism in biopsies of rectus abdominus muscle from lean and obese women.
69	15356065	We also examined the effect of 5-aminoimidazole-4-carboxamide riboside (AICAR) on AMPK activity and the effects of AICAR and leptin on FA metabolism.
70	15356065	However, AMPK mRNA and protein expression, AMPKalpha1 and -alpha2 activities, AMPK kinase activity, ACCbeta phosphorylation, and FA oxidation were similar in lean and obese subjects.
71	15356065	Moreover, AICAR increased AMPKalpha2 activity, ACCbeta phosphorylation, and palmitate oxidation to a similar degree in muscle from lean and obese subjects.
72	15356065	We conclude that the abnormal lipid metabolism and leptin resistance of skeletal muscle of obese subjects is not due to down-regulation of AMPK.
73	15356065	In addition, the similar stimulation by AICAR of AMPK in skeletal muscle of lean and obese subjects suggests that direct pharmacological activation of AMPK may be a therapeutic approach for stimulating FA oxidation in the treatment of human obesity.
74	15677334	To investigate the role of acetyl-CoA carboxylase 2 (ACC2) in the regulation of energy metabolism in adipose tissues, we studied fatty acid and glucose oxidation in primary cultures of adipocytes isolated from wild-type and Acc2-/- mutant mice fed either normal chow or a HF/HC diet.
75	15677334	The mRNA level of glucose transporter 4 (GLUT4) decreased several fold in the adipose tissue of WT mice fed a HF/HC diet; however, in the adipose tissue of Acc2-/- mutant mice, it was 7-fold higher.
76	15677334	These findings suggest that continuous fatty acid oxidation in the adipocytes of Acc2-/- mutant mice, combined with a higher level of glucose oxidation and a higher rate of lipolysis, are major factors leading to efficient maintenance of insulin sensitivity and leaner Acc2-/- mutant mice.
77	15769985	In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2.
78	15769985	In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects.
79	15769985	Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052).
80	15769985	In lean myotubes, gAD activates AMPKalpha1 and -alpha2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACCbeta) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside.
81	15769985	In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 mug/ml) was blunted, but higher concentrations (0.5 mug/ml) stimulated AMPKalpha1 and -alpha2 activities, AMPK and ACCbeta phosphorylation, and fatty acid oxidation.
82	15769985	In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPKalpha1 activity and AMPK phosphorylation; however, ACCbeta phosphorylation and fatty acid oxidation were unaffected.
83	15769985	Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPKalpha and ACCbeta or the expression and activity of the upstream AMPK kinase, LKB1.
84	15769985	These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
85	15769985	In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2.
86	15769985	In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects.
87	15769985	Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052).
88	15769985	In lean myotubes, gAD activates AMPKalpha1 and -alpha2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACCbeta) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside.
89	15769985	In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 mug/ml) was blunted, but higher concentrations (0.5 mug/ml) stimulated AMPKalpha1 and -alpha2 activities, AMPK and ACCbeta phosphorylation, and fatty acid oxidation.
90	15769985	In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPKalpha1 activity and AMPK phosphorylation; however, ACCbeta phosphorylation and fatty acid oxidation were unaffected.
91	15769985	Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPKalpha and ACCbeta or the expression and activity of the upstream AMPK kinase, LKB1.
92	15769985	These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
93	15769985	In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2.
94	15769985	In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects.
95	15769985	Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052).
96	15769985	In lean myotubes, gAD activates AMPKalpha1 and -alpha2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACCbeta) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside.
97	15769985	In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 mug/ml) was blunted, but higher concentrations (0.5 mug/ml) stimulated AMPKalpha1 and -alpha2 activities, AMPK and ACCbeta phosphorylation, and fatty acid oxidation.
98	15769985	In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPKalpha1 activity and AMPK phosphorylation; however, ACCbeta phosphorylation and fatty acid oxidation were unaffected.
99	15769985	Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPKalpha and ACCbeta or the expression and activity of the upstream AMPK kinase, LKB1.
100	15769985	These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
101	15769985	In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2.
102	15769985	In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects.
103	15769985	Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052).
104	15769985	In lean myotubes, gAD activates AMPKalpha1 and -alpha2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACCbeta) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside.
105	15769985	In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 mug/ml) was blunted, but higher concentrations (0.5 mug/ml) stimulated AMPKalpha1 and -alpha2 activities, AMPK and ACCbeta phosphorylation, and fatty acid oxidation.
106	15769985	In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPKalpha1 activity and AMPK phosphorylation; however, ACCbeta phosphorylation and fatty acid oxidation were unaffected.
107	15769985	Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPKalpha and ACCbeta or the expression and activity of the upstream AMPK kinase, LKB1.
108	15769985	These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
109	15934915	Studies in ACC2 knockout mice and in experimental animals treated with isozyme-nonselective ACC inhibitors have demonstrated the potential for treating metabolic syndrome through this modality.
110	15968460	Mice deficient in ACC2 have continuous fatty acid oxidation and reduced body fat and body weight, validating this enzyme as a target for drug development against obesity, diabetes and other symptoms of the metabolic syndrome.
111	15968460	ACC is a biotin-dependent enzyme and catalyzes the carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase (BC) and carboxyltransferase (CT).
112	16485039	Malonyl-CoA, generated by acetyl-CoA carboxylases 1 and 2 (Acc1 and Acc2), is a key regulator of both mitochondrial fatty acid oxidation and fat synthesis.
113	16485039	We used a diet-induced rat model of nonalcoholic fatty liver disease (NAFLD) and hepatic insulin resistance to explore the impact of suppressing Acc1, Acc2, or both Acc1 and Acc2 on hepatic lipid levels and insulin sensitivity.
114	16485039	While suppression of Acc1 or Acc2 expression with antisense oligonucleotides (ASOs) increased fat oxidation in rat hepatocytes, suppression of both enzymes with a single ASO was significantly more effective in promoting fat oxidation.
115	16485039	These studies suggest that pharmacological inhibition of Acc1 and -2 may be a novel approach in the treatment of NAFLD and hepatic insulin resistance.
116	16485039	Malonyl-CoA, generated by acetyl-CoA carboxylases 1 and 2 (Acc1 and Acc2), is a key regulator of both mitochondrial fatty acid oxidation and fat synthesis.
117	16485039	We used a diet-induced rat model of nonalcoholic fatty liver disease (NAFLD) and hepatic insulin resistance to explore the impact of suppressing Acc1, Acc2, or both Acc1 and Acc2 on hepatic lipid levels and insulin sensitivity.
118	16485039	While suppression of Acc1 or Acc2 expression with antisense oligonucleotides (ASOs) increased fat oxidation in rat hepatocytes, suppression of both enzymes with a single ASO was significantly more effective in promoting fat oxidation.
119	16485039	These studies suggest that pharmacological inhibition of Acc1 and -2 may be a novel approach in the treatment of NAFLD and hepatic insulin resistance.
120	16485039	Malonyl-CoA, generated by acetyl-CoA carboxylases 1 and 2 (Acc1 and Acc2), is a key regulator of both mitochondrial fatty acid oxidation and fat synthesis.
121	16485039	We used a diet-induced rat model of nonalcoholic fatty liver disease (NAFLD) and hepatic insulin resistance to explore the impact of suppressing Acc1, Acc2, or both Acc1 and Acc2 on hepatic lipid levels and insulin sensitivity.
122	16485039	While suppression of Acc1 or Acc2 expression with antisense oligonucleotides (ASOs) increased fat oxidation in rat hepatocytes, suppression of both enzymes with a single ASO was significantly more effective in promoting fat oxidation.
123	16485039	These studies suggest that pharmacological inhibition of Acc1 and -2 may be a novel approach in the treatment of NAFLD and hepatic insulin resistance.
124	16721829	Employing quantitative real-time PCR, we determined that expression of mitochondrial acetyl-CoA carboxylase 2 (ACC2) was increased by 50% with obesity (P < 0.05).
125	16721829	In both lean and obese subjects, expression of mitochondrial ACC2 was 20-fold greater than that of cytoplasmic ACC1, consistent with their hypothesized roles in synthesizing malonyl-CoA from acetyl-CoA for CPT1 regulation and lipogenesis, respectively.
126	16721829	In addition, in both lean and obese subjects, expression of malonyl-CoA decarboxylase was approximately 40-fold greater than fatty acid synthase, consistent with degradation, rather than lipogenesis, being the primary fate of malonyl-CoA in human muscle.
127	16721829	Employing quantitative real-time PCR, we determined that expression of mitochondrial acetyl-CoA carboxylase 2 (ACC2) was increased by 50% with obesity (P < 0.05).
128	16721829	In both lean and obese subjects, expression of mitochondrial ACC2 was 20-fold greater than that of cytoplasmic ACC1, consistent with their hypothesized roles in synthesizing malonyl-CoA from acetyl-CoA for CPT1 regulation and lipogenesis, respectively.
129	16721829	In addition, in both lean and obese subjects, expression of malonyl-CoA decarboxylase was approximately 40-fold greater than fatty acid synthase, consistent with degradation, rather than lipogenesis, being the primary fate of malonyl-CoA in human muscle.
130	16854592	Acetyl coenzyme A (acetyl-CoA) carboxylase isozyme 1 (ACC1) and acetyl-CoA carboxylase isozyme 2 (ACC2) are critical for de novo fatty acid synthesis and for the regulation of beta-oxidation.
131	16854592	The resultant human ACC2, human ACC1, and rat ACC2 possess high specific activities, are properly biotinylated, and exhibit kinetic parameters very similar to the native ACC enzymes.
132	16854592	Acetyl coenzyme A (acetyl-CoA) carboxylase isozyme 1 (ACC1) and acetyl-CoA carboxylase isozyme 2 (ACC2) are critical for de novo fatty acid synthesis and for the regulation of beta-oxidation.
133	16854592	The resultant human ACC2, human ACC1, and rat ACC2 possess high specific activities, are properly biotinylated, and exhibit kinetic parameters very similar to the native ACC enzymes.
134	17923673	Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity.
135	17923673	Acetyl-CoA carboxylase 2 (ACC)2 is a key regulator of mitochondrial fat oxidation.
136	17923673	To examine the impact of ACC2 deletion on whole-body energy metabolism, we measured changes in substrate oxidation and total energy expenditure in Acc2(-/-) and WT control mice fed either regular or high-fat diets.
137	17923673	To determine insulin action in vivo, we also measured whole-body insulin-stimulated liver and muscle glucose metabolism during a hyperinsulinemic-euglycemic clamp in Acc2(-/-) and WT control mice fed a high-fat diet.
138	17923673	Contrary to previous studies that have suggested that increased fat oxidation might result in lower glucose oxidation, both fat and carbohydrate oxidation were simultaneously increased in Acc2(-/-) mice.
139	17923673	Furthermore, Acc2(-/-) mice were protected from fat-induced peripheral and hepatic insulin resistance.
140	17923673	Taken together with previous work demonstrating that Acc2(-/-) mice have a normal lifespan, these data suggest that Acc2 inhibition is a viable therapeutic option for the treatment of obesity and type 2 diabetes.
141	17923673	Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity.
142	17923673	Acetyl-CoA carboxylase 2 (ACC)2 is a key regulator of mitochondrial fat oxidation.
143	17923673	To examine the impact of ACC2 deletion on whole-body energy metabolism, we measured changes in substrate oxidation and total energy expenditure in Acc2(-/-) and WT control mice fed either regular or high-fat diets.
144	17923673	To determine insulin action in vivo, we also measured whole-body insulin-stimulated liver and muscle glucose metabolism during a hyperinsulinemic-euglycemic clamp in Acc2(-/-) and WT control mice fed a high-fat diet.
145	17923673	Contrary to previous studies that have suggested that increased fat oxidation might result in lower glucose oxidation, both fat and carbohydrate oxidation were simultaneously increased in Acc2(-/-) mice.
146	17923673	Furthermore, Acc2(-/-) mice were protected from fat-induced peripheral and hepatic insulin resistance.
147	17923673	Taken together with previous work demonstrating that Acc2(-/-) mice have a normal lifespan, these data suggest that Acc2 inhibition is a viable therapeutic option for the treatment of obesity and type 2 diabetes.
148	17923673	Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity.
149	17923673	Acetyl-CoA carboxylase 2 (ACC)2 is a key regulator of mitochondrial fat oxidation.
150	17923673	To examine the impact of ACC2 deletion on whole-body energy metabolism, we measured changes in substrate oxidation and total energy expenditure in Acc2(-/-) and WT control mice fed either regular or high-fat diets.
151	17923673	To determine insulin action in vivo, we also measured whole-body insulin-stimulated liver and muscle glucose metabolism during a hyperinsulinemic-euglycemic clamp in Acc2(-/-) and WT control mice fed a high-fat diet.
152	17923673	Contrary to previous studies that have suggested that increased fat oxidation might result in lower glucose oxidation, both fat and carbohydrate oxidation were simultaneously increased in Acc2(-/-) mice.
153	17923673	Furthermore, Acc2(-/-) mice were protected from fat-induced peripheral and hepatic insulin resistance.
154	17923673	Taken together with previous work demonstrating that Acc2(-/-) mice have a normal lifespan, these data suggest that Acc2 inhibition is a viable therapeutic option for the treatment of obesity and type 2 diabetes.
155	17923673	Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity.
156	17923673	Acetyl-CoA carboxylase 2 (ACC)2 is a key regulator of mitochondrial fat oxidation.
157	17923673	To examine the impact of ACC2 deletion on whole-body energy metabolism, we measured changes in substrate oxidation and total energy expenditure in Acc2(-/-) and WT control mice fed either regular or high-fat diets.
158	17923673	To determine insulin action in vivo, we also measured whole-body insulin-stimulated liver and muscle glucose metabolism during a hyperinsulinemic-euglycemic clamp in Acc2(-/-) and WT control mice fed a high-fat diet.
159	17923673	Contrary to previous studies that have suggested that increased fat oxidation might result in lower glucose oxidation, both fat and carbohydrate oxidation were simultaneously increased in Acc2(-/-) mice.
160	17923673	Furthermore, Acc2(-/-) mice were protected from fat-induced peripheral and hepatic insulin resistance.
161	17923673	Taken together with previous work demonstrating that Acc2(-/-) mice have a normal lifespan, these data suggest that Acc2 inhibition is a viable therapeutic option for the treatment of obesity and type 2 diabetes.
162	17923673	Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity.
163	17923673	Acetyl-CoA carboxylase 2 (ACC)2 is a key regulator of mitochondrial fat oxidation.
164	17923673	To examine the impact of ACC2 deletion on whole-body energy metabolism, we measured changes in substrate oxidation and total energy expenditure in Acc2(-/-) and WT control mice fed either regular or high-fat diets.
165	17923673	To determine insulin action in vivo, we also measured whole-body insulin-stimulated liver and muscle glucose metabolism during a hyperinsulinemic-euglycemic clamp in Acc2(-/-) and WT control mice fed a high-fat diet.
166	17923673	Contrary to previous studies that have suggested that increased fat oxidation might result in lower glucose oxidation, both fat and carbohydrate oxidation were simultaneously increased in Acc2(-/-) mice.
167	17923673	Furthermore, Acc2(-/-) mice were protected from fat-induced peripheral and hepatic insulin resistance.
168	17923673	Taken together with previous work demonstrating that Acc2(-/-) mice have a normal lifespan, these data suggest that Acc2 inhibition is a viable therapeutic option for the treatment of obesity and type 2 diabetes.
169	17923673	Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity.
170	17923673	Acetyl-CoA carboxylase 2 (ACC)2 is a key regulator of mitochondrial fat oxidation.
171	17923673	To examine the impact of ACC2 deletion on whole-body energy metabolism, we measured changes in substrate oxidation and total energy expenditure in Acc2(-/-) and WT control mice fed either regular or high-fat diets.
172	17923673	To determine insulin action in vivo, we also measured whole-body insulin-stimulated liver and muscle glucose metabolism during a hyperinsulinemic-euglycemic clamp in Acc2(-/-) and WT control mice fed a high-fat diet.
173	17923673	Contrary to previous studies that have suggested that increased fat oxidation might result in lower glucose oxidation, both fat and carbohydrate oxidation were simultaneously increased in Acc2(-/-) mice.
174	17923673	Furthermore, Acc2(-/-) mice were protected from fat-induced peripheral and hepatic insulin resistance.
175	17923673	Taken together with previous work demonstrating that Acc2(-/-) mice have a normal lifespan, these data suggest that Acc2 inhibition is a viable therapeutic option for the treatment of obesity and type 2 diabetes.
176	17923673	Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity.
177	17923673	Acetyl-CoA carboxylase 2 (ACC)2 is a key regulator of mitochondrial fat oxidation.
178	17923673	To examine the impact of ACC2 deletion on whole-body energy metabolism, we measured changes in substrate oxidation and total energy expenditure in Acc2(-/-) and WT control mice fed either regular or high-fat diets.
179	17923673	To determine insulin action in vivo, we also measured whole-body insulin-stimulated liver and muscle glucose metabolism during a hyperinsulinemic-euglycemic clamp in Acc2(-/-) and WT control mice fed a high-fat diet.
180	17923673	Contrary to previous studies that have suggested that increased fat oxidation might result in lower glucose oxidation, both fat and carbohydrate oxidation were simultaneously increased in Acc2(-/-) mice.
181	17923673	Furthermore, Acc2(-/-) mice were protected from fat-induced peripheral and hepatic insulin resistance.
182	17923673	Taken together with previous work demonstrating that Acc2(-/-) mice have a normal lifespan, these data suggest that Acc2 inhibition is a viable therapeutic option for the treatment of obesity and type 2 diabetes.
183	18025247	Acetyl CoA carboxylase (ACC) 2, which catalyzes the carboxylation of acetyl-CoA to form malonyl-CoA, has been identified as a potential target for type 2 diabetes and obesity.
184	18025247	Small-molecule inhibitors of ACC2 would be expected to reduce de novo lipid synthesis and increase lipid oxidation.
185	18025247	Treatment of ob/ob mice with compound A-908292 (S) ({(S)-3-[2-(4-isopropoxy-phenoxy)-thiazol-5-yl]-1-methyl-prop-2-ynyl}-carbamic acid methyl ester), a small-molecule inhibitor with an IC(50) of 23 nM against ACC2, resulted in a reduction of serum glucose and triglyceride levels.
186	18025247	However, compound A-875400 (R) ({(R)-3-[2-(4-isopropoxy-phenoxy)-thiazol-5-yl]-1-methyl-prop-2-ynyl}-carbamic acid methyl ester), an inactive enantiomer of A-908292 (S) with approximately 50-fold less activity against ACC2, also caused a similar reduction in glucose and triglycerides, suggesting that the glucose-lowering effects in ob/ob mice may be mediated by other metabolic pathways independent of ACC2 inhibition.
187	18025247	Overall, the gene expression analysis suggests a plausible mechanism for the similar pharmacological findings with active and inactive enantiomers of an ACC2 inhibitor.
188	18025247	Acetyl CoA carboxylase (ACC) 2, which catalyzes the carboxylation of acetyl-CoA to form malonyl-CoA, has been identified as a potential target for type 2 diabetes and obesity.
189	18025247	Small-molecule inhibitors of ACC2 would be expected to reduce de novo lipid synthesis and increase lipid oxidation.
190	18025247	Treatment of ob/ob mice with compound A-908292 (S) ({(S)-3-[2-(4-isopropoxy-phenoxy)-thiazol-5-yl]-1-methyl-prop-2-ynyl}-carbamic acid methyl ester), a small-molecule inhibitor with an IC(50) of 23 nM against ACC2, resulted in a reduction of serum glucose and triglyceride levels.
191	18025247	However, compound A-875400 (R) ({(R)-3-[2-(4-isopropoxy-phenoxy)-thiazol-5-yl]-1-methyl-prop-2-ynyl}-carbamic acid methyl ester), an inactive enantiomer of A-908292 (S) with approximately 50-fold less activity against ACC2, also caused a similar reduction in glucose and triglycerides, suggesting that the glucose-lowering effects in ob/ob mice may be mediated by other metabolic pathways independent of ACC2 inhibition.
192	18025247	Overall, the gene expression analysis suggests a plausible mechanism for the similar pharmacological findings with active and inactive enantiomers of an ACC2 inhibitor.
193	18025247	Acetyl CoA carboxylase (ACC) 2, which catalyzes the carboxylation of acetyl-CoA to form malonyl-CoA, has been identified as a potential target for type 2 diabetes and obesity.
194	18025247	Small-molecule inhibitors of ACC2 would be expected to reduce de novo lipid synthesis and increase lipid oxidation.
195	18025247	Treatment of ob/ob mice with compound A-908292 (S) ({(S)-3-[2-(4-isopropoxy-phenoxy)-thiazol-5-yl]-1-methyl-prop-2-ynyl}-carbamic acid methyl ester), a small-molecule inhibitor with an IC(50) of 23 nM against ACC2, resulted in a reduction of serum glucose and triglyceride levels.
196	18025247	However, compound A-875400 (R) ({(R)-3-[2-(4-isopropoxy-phenoxy)-thiazol-5-yl]-1-methyl-prop-2-ynyl}-carbamic acid methyl ester), an inactive enantiomer of A-908292 (S) with approximately 50-fold less activity against ACC2, also caused a similar reduction in glucose and triglycerides, suggesting that the glucose-lowering effects in ob/ob mice may be mediated by other metabolic pathways independent of ACC2 inhibition.
197	18025247	Overall, the gene expression analysis suggests a plausible mechanism for the similar pharmacological findings with active and inactive enantiomers of an ACC2 inhibitor.
198	18025247	Acetyl CoA carboxylase (ACC) 2, which catalyzes the carboxylation of acetyl-CoA to form malonyl-CoA, has been identified as a potential target for type 2 diabetes and obesity.
199	18025247	Small-molecule inhibitors of ACC2 would be expected to reduce de novo lipid synthesis and increase lipid oxidation.
200	18025247	Treatment of ob/ob mice with compound A-908292 (S) ({(S)-3-[2-(4-isopropoxy-phenoxy)-thiazol-5-yl]-1-methyl-prop-2-ynyl}-carbamic acid methyl ester), a small-molecule inhibitor with an IC(50) of 23 nM against ACC2, resulted in a reduction of serum glucose and triglyceride levels.
201	18025247	However, compound A-875400 (R) ({(R)-3-[2-(4-isopropoxy-phenoxy)-thiazol-5-yl]-1-methyl-prop-2-ynyl}-carbamic acid methyl ester), an inactive enantiomer of A-908292 (S) with approximately 50-fold less activity against ACC2, also caused a similar reduction in glucose and triglycerides, suggesting that the glucose-lowering effects in ob/ob mice may be mediated by other metabolic pathways independent of ACC2 inhibition.
202	18025247	Overall, the gene expression analysis suggests a plausible mechanism for the similar pharmacological findings with active and inactive enantiomers of an ACC2 inhibitor.
203	18221116	Studies in ACC2 knockout mice and in experimental animals treated with isozyme-specific antisense oligonucleotides or with isozyme-nonselective ACC inhibitors have demonstrated the potential for treating metabolic syndrome through this modality.
204	18221116	Co-crystallization of the biotin carboxylase and carboxyltransferase domains of eukaryotic ACC in the presence of substrates and inhibitors has revealed characteristics of the catalytic center that can be exploited in drug discovery.
205	19047759	Acetyl-CoA carboxylases 1 and 2 (ACC1 and ACC2) catalyze the synthesis of malonyl-CoA, the substrate for fatty acid synthesis and the regulator of fatty acid oxidation.
206	19047759	In this review we discuss the role of fatty acid metabolism and its key players, ACC1 and ACC2, in animal evolution and physiology, as related to health and disease.
207	19047759	Acetyl-CoA carboxylases 1 and 2 (ACC1 and ACC2) catalyze the synthesis of malonyl-CoA, the substrate for fatty acid synthesis and the regulator of fatty acid oxidation.
208	19047759	In this review we discuss the role of fatty acid metabolism and its key players, ACC1 and ACC2, in animal evolution and physiology, as related to health and disease.
209	19390150	The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist.
210	19390150	Inhibition of acetyl-CoA carboxylase (ACC) may prevent lipid-induced insulin resistance and type 2 diabetes, making the enzyme an attractive pharmaceutical target.
211	19390150	The use of biophysical assays has permitted the identification of a specific C-terminal truncation of the 826-residue human ACC2 carboxyl transferase (CT) domain that is both functionally competent to bind inhibitors and crystallizes in their presence.
212	19390150	This C-terminal truncation led to the determination of the human ACC2 CT domain-CP-640186 complex crystal structure, which revealed distinctions from the yeast-enzyme complex.
213	19390150	The human ACC2 CT-domain C-terminus is comprised of three intertwined alpha-helices that extend outwards from the enzyme on the opposite side to the ligand-binding site.
214	19390150	The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist.
215	19390150	Inhibition of acetyl-CoA carboxylase (ACC) may prevent lipid-induced insulin resistance and type 2 diabetes, making the enzyme an attractive pharmaceutical target.
216	19390150	The use of biophysical assays has permitted the identification of a specific C-terminal truncation of the 826-residue human ACC2 carboxyl transferase (CT) domain that is both functionally competent to bind inhibitors and crystallizes in their presence.
217	19390150	This C-terminal truncation led to the determination of the human ACC2 CT domain-CP-640186 complex crystal structure, which revealed distinctions from the yeast-enzyme complex.
218	19390150	The human ACC2 CT-domain C-terminus is comprised of three intertwined alpha-helices that extend outwards from the enzyme on the opposite side to the ligand-binding site.
219	19390150	The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist.
220	19390150	Inhibition of acetyl-CoA carboxylase (ACC) may prevent lipid-induced insulin resistance and type 2 diabetes, making the enzyme an attractive pharmaceutical target.
221	19390150	The use of biophysical assays has permitted the identification of a specific C-terminal truncation of the 826-residue human ACC2 carboxyl transferase (CT) domain that is both functionally competent to bind inhibitors and crystallizes in their presence.
222	19390150	This C-terminal truncation led to the determination of the human ACC2 CT domain-CP-640186 complex crystal structure, which revealed distinctions from the yeast-enzyme complex.
223	19390150	The human ACC2 CT-domain C-terminus is comprised of three intertwined alpha-helices that extend outwards from the enzyme on the opposite side to the ligand-binding site.
224	19390150	The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist.
225	19390150	Inhibition of acetyl-CoA carboxylase (ACC) may prevent lipid-induced insulin resistance and type 2 diabetes, making the enzyme an attractive pharmaceutical target.
226	19390150	The use of biophysical assays has permitted the identification of a specific C-terminal truncation of the 826-residue human ACC2 carboxyl transferase (CT) domain that is both functionally competent to bind inhibitors and crystallizes in their presence.
227	19390150	This C-terminal truncation led to the determination of the human ACC2 CT domain-CP-640186 complex crystal structure, which revealed distinctions from the yeast-enzyme complex.
228	19390150	The human ACC2 CT-domain C-terminus is comprised of three intertwined alpha-helices that extend outwards from the enzyme on the opposite side to the ligand-binding site.
229	19748969	Brain-derived neurotrophic factor mRNA and protein expression was increased in muscle cells that were electrically stimulated, and BDNF increased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl coenzyme A carboxylase-beta (ACCbeta) and enhanced fatty oxidation both in vitro and ex vivo.
230	19748969	These data identify BDNF as a contraction-inducible protein in skeletal muscle that is capable of enhancing lipid oxidation in skeletal muscle via activation of AMPK.
231	21051750	The ACACB gene (also called ACC2 or acetyl-CoA carboxylase 2) plays a critical role in intracellular fatty acid (FA) oxidation.
232	21082864	Acetyl CoA carboxylase isoforms 1 and 2 (ACC1/2) are key enzymes of fat utilization and their inhibition is considered to improve aspects of the metabolic syndrome.
233	21082864	To identify pharmacological inhibitors of ACC1/2, a high throughput screen was performed which resulted in the identification of the lead compound 3 ( Gargazanli , G. ; Lardenois , P. ; Frost , J. ; George , P.
234	21082864	Patent WO9855474 A1, 1998 ) as a moderate selective ACC2 inhibitor.
235	21082864	Patent WO2010003624 A2, 2010 ) as a submicromolar dual ACC1/2 inhibitor of the rat and human isoforms. 4m possessed favorable pharmacokinetic parameters.
236	21082864	This compound stimulated fat oxidation in vivo and reduced plasma triglyceride levels in a rodent model after subchronic administration. 4m is a suitable tool compound for the elucidation of the pharmacological potential of ACC1/2 inhibition.
237	21515056	Hybridization of weak inhibitors of ACC2 provided a novel, moderately potent but lipophilic series.
238	21515056	Optimization led to compounds 33 and 37, which exhibit potent inhibition of human ACC2, 10-fold selectivity over inhibition of human ACC1, good physical and in vitro ADME properties and good bioavailability.
239	21515056	X-ray crystallography has shown this series binding in the CT-domain of ACC2 and revealed two key hydrogen bonding interactions.
240	21515056	Hybridization of weak inhibitors of ACC2 provided a novel, moderately potent but lipophilic series.
241	21515056	Optimization led to compounds 33 and 37, which exhibit potent inhibition of human ACC2, 10-fold selectivity over inhibition of human ACC1, good physical and in vitro ADME properties and good bioavailability.
242	21515056	X-ray crystallography has shown this series binding in the CT-domain of ACC2 and revealed two key hydrogen bonding interactions.
243	21515056	Hybridization of weak inhibitors of ACC2 provided a novel, moderately potent but lipophilic series.
244	21515056	Optimization led to compounds 33 and 37, which exhibit potent inhibition of human ACC2, 10-fold selectivity over inhibition of human ACC1, good physical and in vitro ADME properties and good bioavailability.
245	21515056	X-ray crystallography has shown this series binding in the CT-domain of ACC2 and revealed two key hydrogen bonding interactions.
246	21553357	A gene polymorphism in acetyl-coenzyme A carboxylase beta may be associated with the C-reactive protein level in a prediabetic and diabetic population.
247	21553357	Considering the involvement of chronic inflammation in the pathophysiology of DM, the present study investigated an association between the ACACB gene polymorphism and high-sensitivity C-reactive protein (hsCRP) in a prediabetic and diabetic population.
248	21553357	A gene polymorphism in acetyl-coenzyme A carboxylase beta may be associated with the C-reactive protein level in a prediabetic and diabetic population.
249	21553357	Considering the involvement of chronic inflammation in the pathophysiology of DM, the present study investigated an association between the ACACB gene polymorphism and high-sensitivity C-reactive protein (hsCRP) in a prediabetic and diabetic population.
250	22362781	We have shown previously that acetyl-CoA carboxylase 2 (Acc2(-/-)) mutant mice, when fed a high-fat (HF) or high-fat, high-carbohydrate (HFHC) diet, are protected against diet-induced obesity and maintained whole body and hepatic insulin sensitivity.
251	22362781	To determine the effect of an ACC2 deletion on hepatic fat metabolism, we studied the regulation of the enzymes involved in the lipogenic pathway under Western HFHC dietary and de novo lipogenic conditions.
252	22362781	After completing the HFHC regimen, Acc2(-/-) mutant mice were found to have lower body weight, smaller epididymal fat pads, lower blood levels of nonesterified fatty acids and triglycerides, and higher hepatic cholesterol than wild-type mice.
253	22362781	Significant up-regulation of lipogenic enzymes and an elevation in hepatic peroxisome proliferator-activated receptor-γ (PPAR-γ) protein were found in Acc2(-/-) mutant mice under de novo lipogenic conditions.
254	22362781	In contrast, hepatic levels of the PPAR-γ and PPAR-α proteins were significantly lower in the Acc2(-/-) mutant mice fed an HFHC diet.
255	22362781	When compared with wild-type mice fed the same diet, Acc2(-/-) mutant mice exhibited a similar level of AKT but with a significant increase in pAKT.
256	22362781	Hence, deleting ACC2 ameliorates the metabolic syndrome and protects against fatty liver despite increased de novo lipogenesis and dietary conditions known to induce obesity and diabetes.
257	22362781	We have shown previously that acetyl-CoA carboxylase 2 (Acc2(-/-)) mutant mice, when fed a high-fat (HF) or high-fat, high-carbohydrate (HFHC) diet, are protected against diet-induced obesity and maintained whole body and hepatic insulin sensitivity.
258	22362781	To determine the effect of an ACC2 deletion on hepatic fat metabolism, we studied the regulation of the enzymes involved in the lipogenic pathway under Western HFHC dietary and de novo lipogenic conditions.
259	22362781	After completing the HFHC regimen, Acc2(-/-) mutant mice were found to have lower body weight, smaller epididymal fat pads, lower blood levels of nonesterified fatty acids and triglycerides, and higher hepatic cholesterol than wild-type mice.
260	22362781	Significant up-regulation of lipogenic enzymes and an elevation in hepatic peroxisome proliferator-activated receptor-γ (PPAR-γ) protein were found in Acc2(-/-) mutant mice under de novo lipogenic conditions.
261	22362781	In contrast, hepatic levels of the PPAR-γ and PPAR-α proteins were significantly lower in the Acc2(-/-) mutant mice fed an HFHC diet.
262	22362781	When compared with wild-type mice fed the same diet, Acc2(-/-) mutant mice exhibited a similar level of AKT but with a significant increase in pAKT.
263	22362781	Hence, deleting ACC2 ameliorates the metabolic syndrome and protects against fatty liver despite increased de novo lipogenesis and dietary conditions known to induce obesity and diabetes.
264	22362781	We have shown previously that acetyl-CoA carboxylase 2 (Acc2(-/-)) mutant mice, when fed a high-fat (HF) or high-fat, high-carbohydrate (HFHC) diet, are protected against diet-induced obesity and maintained whole body and hepatic insulin sensitivity.
265	22362781	To determine the effect of an ACC2 deletion on hepatic fat metabolism, we studied the regulation of the enzymes involved in the lipogenic pathway under Western HFHC dietary and de novo lipogenic conditions.
266	22362781	After completing the HFHC regimen, Acc2(-/-) mutant mice were found to have lower body weight, smaller epididymal fat pads, lower blood levels of nonesterified fatty acids and triglycerides, and higher hepatic cholesterol than wild-type mice.
267	22362781	Significant up-regulation of lipogenic enzymes and an elevation in hepatic peroxisome proliferator-activated receptor-γ (PPAR-γ) protein were found in Acc2(-/-) mutant mice under de novo lipogenic conditions.
268	22362781	In contrast, hepatic levels of the PPAR-γ and PPAR-α proteins were significantly lower in the Acc2(-/-) mutant mice fed an HFHC diet.
269	22362781	When compared with wild-type mice fed the same diet, Acc2(-/-) mutant mice exhibited a similar level of AKT but with a significant increase in pAKT.
270	22362781	Hence, deleting ACC2 ameliorates the metabolic syndrome and protects against fatty liver despite increased de novo lipogenesis and dietary conditions known to induce obesity and diabetes.
271	22362781	We have shown previously that acetyl-CoA carboxylase 2 (Acc2(-/-)) mutant mice, when fed a high-fat (HF) or high-fat, high-carbohydrate (HFHC) diet, are protected against diet-induced obesity and maintained whole body and hepatic insulin sensitivity.
272	22362781	To determine the effect of an ACC2 deletion on hepatic fat metabolism, we studied the regulation of the enzymes involved in the lipogenic pathway under Western HFHC dietary and de novo lipogenic conditions.
273	22362781	After completing the HFHC regimen, Acc2(-/-) mutant mice were found to have lower body weight, smaller epididymal fat pads, lower blood levels of nonesterified fatty acids and triglycerides, and higher hepatic cholesterol than wild-type mice.
274	22362781	Significant up-regulation of lipogenic enzymes and an elevation in hepatic peroxisome proliferator-activated receptor-γ (PPAR-γ) protein were found in Acc2(-/-) mutant mice under de novo lipogenic conditions.
275	22362781	In contrast, hepatic levels of the PPAR-γ and PPAR-α proteins were significantly lower in the Acc2(-/-) mutant mice fed an HFHC diet.
276	22362781	When compared with wild-type mice fed the same diet, Acc2(-/-) mutant mice exhibited a similar level of AKT but with a significant increase in pAKT.
277	22362781	Hence, deleting ACC2 ameliorates the metabolic syndrome and protects against fatty liver despite increased de novo lipogenesis and dietary conditions known to induce obesity and diabetes.
278	22362781	We have shown previously that acetyl-CoA carboxylase 2 (Acc2(-/-)) mutant mice, when fed a high-fat (HF) or high-fat, high-carbohydrate (HFHC) diet, are protected against diet-induced obesity and maintained whole body and hepatic insulin sensitivity.
279	22362781	To determine the effect of an ACC2 deletion on hepatic fat metabolism, we studied the regulation of the enzymes involved in the lipogenic pathway under Western HFHC dietary and de novo lipogenic conditions.
280	22362781	After completing the HFHC regimen, Acc2(-/-) mutant mice were found to have lower body weight, smaller epididymal fat pads, lower blood levels of nonesterified fatty acids and triglycerides, and higher hepatic cholesterol than wild-type mice.
281	22362781	Significant up-regulation of lipogenic enzymes and an elevation in hepatic peroxisome proliferator-activated receptor-γ (PPAR-γ) protein were found in Acc2(-/-) mutant mice under de novo lipogenic conditions.
282	22362781	In contrast, hepatic levels of the PPAR-γ and PPAR-α proteins were significantly lower in the Acc2(-/-) mutant mice fed an HFHC diet.
283	22362781	When compared with wild-type mice fed the same diet, Acc2(-/-) mutant mice exhibited a similar level of AKT but with a significant increase in pAKT.
284	22362781	Hence, deleting ACC2 ameliorates the metabolic syndrome and protects against fatty liver despite increased de novo lipogenesis and dietary conditions known to induce obesity and diabetes.
285	22362781	We have shown previously that acetyl-CoA carboxylase 2 (Acc2(-/-)) mutant mice, when fed a high-fat (HF) or high-fat, high-carbohydrate (HFHC) diet, are protected against diet-induced obesity and maintained whole body and hepatic insulin sensitivity.
286	22362781	To determine the effect of an ACC2 deletion on hepatic fat metabolism, we studied the regulation of the enzymes involved in the lipogenic pathway under Western HFHC dietary and de novo lipogenic conditions.
287	22362781	After completing the HFHC regimen, Acc2(-/-) mutant mice were found to have lower body weight, smaller epididymal fat pads, lower blood levels of nonesterified fatty acids and triglycerides, and higher hepatic cholesterol than wild-type mice.
288	22362781	Significant up-regulation of lipogenic enzymes and an elevation in hepatic peroxisome proliferator-activated receptor-γ (PPAR-γ) protein were found in Acc2(-/-) mutant mice under de novo lipogenic conditions.
289	22362781	In contrast, hepatic levels of the PPAR-γ and PPAR-α proteins were significantly lower in the Acc2(-/-) mutant mice fed an HFHC diet.
290	22362781	When compared with wild-type mice fed the same diet, Acc2(-/-) mutant mice exhibited a similar level of AKT but with a significant increase in pAKT.
291	22362781	Hence, deleting ACC2 ameliorates the metabolic syndrome and protects against fatty liver despite increased de novo lipogenesis and dietary conditions known to induce obesity and diabetes.
292	22362781	We have shown previously that acetyl-CoA carboxylase 2 (Acc2(-/-)) mutant mice, when fed a high-fat (HF) or high-fat, high-carbohydrate (HFHC) diet, are protected against diet-induced obesity and maintained whole body and hepatic insulin sensitivity.
293	22362781	To determine the effect of an ACC2 deletion on hepatic fat metabolism, we studied the regulation of the enzymes involved in the lipogenic pathway under Western HFHC dietary and de novo lipogenic conditions.
294	22362781	After completing the HFHC regimen, Acc2(-/-) mutant mice were found to have lower body weight, smaller epididymal fat pads, lower blood levels of nonesterified fatty acids and triglycerides, and higher hepatic cholesterol than wild-type mice.
295	22362781	Significant up-regulation of lipogenic enzymes and an elevation in hepatic peroxisome proliferator-activated receptor-γ (PPAR-γ) protein were found in Acc2(-/-) mutant mice under de novo lipogenic conditions.
296	22362781	In contrast, hepatic levels of the PPAR-γ and PPAR-α proteins were significantly lower in the Acc2(-/-) mutant mice fed an HFHC diet.
297	22362781	When compared with wild-type mice fed the same diet, Acc2(-/-) mutant mice exhibited a similar level of AKT but with a significant increase in pAKT.
298	22362781	Hence, deleting ACC2 ameliorates the metabolic syndrome and protects against fatty liver despite increased de novo lipogenesis and dietary conditions known to induce obesity and diabetes.
299	23334436	To identify dual inhibitors of Acetyl-CoA carboxylase1 and Acetyl-CoA carboxylase2, a pharmacophore modelling approach has been employed.
300	23334436	The best HypoGen pharmacophore model for ACC2 inhibitors (Hypo1_ACC2) consists of one hydrogen bond acceptor, one hydrophobic aliphatic and one hydrophobic aromatic feature, whereas the best pharmacophore (Hypo1_ACC1) for ACC1 consists of one additional hydrogen-bond donor (HBD) features.
301	23334436	To identify dual inhibitors of Acetyl-CoA carboxylase1 and Acetyl-CoA carboxylase2, a pharmacophore modelling approach has been employed.
302	23334436	The best HypoGen pharmacophore model for ACC2 inhibitors (Hypo1_ACC2) consists of one hydrogen bond acceptor, one hydrophobic aliphatic and one hydrophobic aromatic feature, whereas the best pharmacophore (Hypo1_ACC1) for ACC1 consists of one additional hydrogen-bond donor (HBD) features.
303	23981033	Alterations in lipid metabolism are believed to contribute to insulin resistance; thus inhibition of ACC offers a promising option for intervention in type 2 diabetes mellitus.
304	23981033	The lactam series has improved chemical and metabolic stability relative to our previously reported pyrazoloketone series, while retaining potent inhibition of ACC1 and ACC2.