Ignet

Gene Information

Gene symbol: CS

Gene name: citrate synthase

HGNC ID: 2422

Related Genes

#	Gene Symbol	Number of hits
1	ABCA1	1 hits
2	ACACA	1 hits
3	ACADM	1 hits
4	ACADS	1 hits
5	ADIPOQ	1 hits
6	APLN	1 hits
7	CKB	1 hits
8	CNBP	1 hits
9	COX4I1	1 hits
10	COX8A	1 hits
11	COX8B	1 hits
12	CPT1A	1 hits
13	CROT	1 hits
14	CYCS	1 hits
15	EPO	1 hits
16	ESRRA	1 hits
17	FAS	1 hits
18	FASN	1 hits
19	FGF21	1 hits
20	G6PD	1 hits
21	GAP43	1 hits
22	GLS	1 hits
23	GLS2	1 hits
24	H6PD	1 hits
25	HADH	1 hits
26	HK2	1 hits
27	HMOX1	1 hits
28	HNF1A	1 hits
29	HSPA1A	1 hits
30	IDH3B	1 hits
31	IL1B	1 hits
32	INS	1 hits
33	MAOB	1 hits
34	MAPK1	1 hits
35	MB	1 hits
36	MCTS1	1 hits
37	ME1	1 hits
38	MT-CO1	1 hits
39	MT-ND4	1 hits
40	MYOZ3	1 hits
41	NEFH	1 hits
42	NEFL	1 hits
43	NEFM	1 hits
44	NRF1	1 hits
45	PPARG	1 hits
46	PPARGC1A	1 hits
47	PRKAA1	1 hits
48	PYGM	1 hits
49	RARA	1 hits
50	SIRT1	1 hits
51	SLC16A1	1 hits
52	SLC16A3	1 hits
53	SLC2A4	1 hits
54	SOD2	1 hits
55	STK11	1 hits
56	TFAM	1 hits
57	TUBA1B	1 hits
58	UCP1	1 hits
59	UCP3	1 hits

Related Sentences

#	PMID	Sentence
1	908476	In biopsy samples of the lateral part of the quadriceps femoris muscle of 6 obese diabetic male patients and of 11 obese males with a normal glucose tolerance, the activities of 7 enzymes of energy metabolism were estimated: hexokinase, cytoplasmic glycerol-3-phosphate: NAD dehydrogenase, triosephosphate dehydrogenase, lactate dehydrogenase, citrate synthase, malate dehydrogenase and 3-hydroxyacyl-CoA dehydrogenase.
2	1399970	This training program induced increases of 52% in citrate synthase activity, 66% in hexokinase activity, and 47% in immunoreactive GLUT4 protein concentration in soleus muscles without causing hypertrophy.
3	1399970	Glucose transport activity stimulated maximally with insulin plus contractile activity was increased to roughly the same extent (44%) as GLUT4 protein content in soleus muscle by the treadmill exercise training.
4	1733237	It was previously found that voluntary wheel running induces an increase in the insulin-sensitive glucose transporter, i.e., the GLUT4 isoform, in rat plantaris muscle (K.
5	1733237	The present study was undertaken to determine whether 1) the increase in muscle GLUT4 protein is associated with an increase in maximally stimulated glucose transport activity, 2) a conversion of type IIb to type IIa or type I muscle fibers plays a role in the increase in GLUT4 protein, and 3) an increase in the GLUT1 isoform is a component of the adaptation of muscle to endurance exercise.
6	1733237	Five weeks of voluntary wheel running that resulted in a 33% increase in citrate synthase activity induced a 50% increase in GLUT4 protein in epitrochlearis muscles of female Sprague-Dawley rats.
7	1733237	We conclude that an increase in GLUT4, but not of GLUT1 protein, is a component of the adaptive response of muscle to endurance exercise and that the increase in GLUT4 protein is associated with an increased capacity for glucose transport.
8	2666106	Differential sensitivity to beta-cell secretagogues in cultured rat pancreatic islets exposed to human interleukin-1 beta.
9	2666106	Interleukin-1 (IL-1) has been suggested to be one possible mediator of immunological damage of the beta-cells.
10	2666106	The activities of the glycolytic enzymes hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in control and IL-1-exposed islets.
11	2666106	Treatment with IL-1 also did not impair the activities of NADH+- and NADPH+-dependent glutamate dehydrogenase, glutamate-aspartate transaminase, glutamate-alanine transaminase, citrate synthase, and NAD+-linked isocitrate dehydrogenase.
12	2666106	These combined observations suggest that exposure to IL-1 induces a preferential decrease in glucose-mediated insulin release and mitochondrial glucose metabolism.
13	2666106	It is conceivable that the IL-1-induced suppression and shift in islet metabolism can be an explanation for the beta-cell insensitivity to glucose observed in the early phases of human and experimental insulin-dependent diabetes mellitus.
14	7722501	The specific activities of carnitine palmitoyltransferase I and carnitine acetyltransferase are significantly increased in the crude mitochondrial fraction isolated from the brains of the type II diabetic mice, whereas the specific activity of pyruvate dehydrogenase complex is decreased.
15	7722501	The specific activities of two other mitochondrial enzymes--monoamine oxidase B and citrate synthase--and a cytosolic enzyme--lactate dehydrogenase--are unaltered.
16	7813810	This study investigated changes in levels of mRNAs encoding the three neurofilament (NF) proteins NF-L (low), NF-M (medium), and NF-H (high) and two growth-associated proteins, GAP-43 and T alpha 1 alpha-tubulin, in lumbar dorsal root ganglia of control and streptozocin-induced diabetic rats.
17	7813810	The filters were probed sequentially with 32P-labeled cDNAs encoding NF-L, NF-M, NF-H, GAP-43, T alpha 1 alpha-tubulin, and citrate synthase.
18	7813810	In diabetes, NF-L mRNA levels (2.5- and 4-kilobase [kb] transcripts) were decreased by 35 (P = 0.002) and 34% (P < 0.001), respectively, the NF-H mRNA level was decreased by 65% (P < 0.001), but the NF-M mRNA remained unchanged.
19	7813810	T alpha 1 alpha-tubulin and GAP-43 mRNA levels were reduced by 56 (P < 0.001) and 30% (P < 0.05), respectively.
20	7964275	Superoxide dismutase, catalase and glutathione peroxidase activities in the lymphoid organs of diabetic rats.
21	7964275	The effect of alloxan-induced diabetes on CuZn- and Mn-superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) activities, as well as the content of thiobarbituric acid reactive substances (TBARs) were examined in rat lymphoid organs (mesenteric lymph nodes (MLN), thymus and spleen) and, for comparison, red and white muscle fibres.
22	7964275	The capacity for generation of reduced equivalents was also evaluated by measuring the activities of glucose-6-phosphate dehydrogenase (pentose-phosphate pathway-cytosol) and citrate synthase (Krebs cycle-mitochondria).
23	7964275	In relation to the lymphoid organs, the spleen showed a decrease in the antioxidant enzyme activities (except for glutathione peroxidase), whereas the thymus showed an increased level (except for Mn-SOD), and the MLN presented a reduction in Mn-SOD and catalase activities and an increase in GPX activity caused by diabetes.
24	7971142	The effects of long-term, moderate physical exercise on in vivo glucose uptake, levels of two glucose transporter proteins (GLUT1 and GLUT4) and activities of various key enzymes of energy metabolism were measured in skeletal muscle from streptozotocin-diabetic rats.
25	7971142	In contrast to the complex changes in GMI, GLUT4 levels were reduced in all types of skeletal muscle from diabetic rats with no change in GLUT1 levels.
26	7971142	Streptozotocin induced diabetes significantly reduced the oxidative capacity of skeletal muscle assayed as the activities of citrate synthase, succinate dehydrogenase and cytochrome c oxidase.
27	8159108	The following enzymes were chosen to represent the major energy-generating pathways: lactate dehydrogenase (LDH) and phosphofructokinase (PFK) for glycolysis; citrate synthase (CS) and beta-hydroxyacl-coenzyme A dehydrogenase (beta-OAC) for oxidation; and creatine kinase (CK) and adenylokinase (AK) for high-energy phosphate metabolism.
28	8298516	Diabetes caused a marked decrease of hexokinase activity (48%; 274.23 +/- 18.43 vs 143.29 +/- 10.35 units for control vs diabetic rats) in macrophages and of citrate synthase and glucose-6-phosphate dehydrogenase activities (70%; 321.76 +/- 9.18 vs 96.25 +/- 5.43 units for citrate synthase and 89.43 +/- 2.33 vs 23.13 +/- 1.09 units for G6PDh for control vs diabetic rats) in mesenteric lymph node lymphocytes.
29	8675680	In additional studies, vastus lateralis muscle was obtained by percutaneous biopsy during basal and insulin-stimulated conditions for assay of hexokinase and citrate synthase, and for immunohistochemical labeling of Glut 4.
30	8690147	Glucose transport activity (assessed by net 2-deoxyglucose [2-DG] uptake), net glycogen synthesis, and glucose oxidation were determined in the isolated epitrochlearis muscles in the absence or presence of insulin (13.3 nmol/l).
31	8690147	No significant effects on glucose transporter (GLUT4) protein level or on the activities of hexokinase and citrate synthase were observed.
32	9124341	Five days of swim training (2 x 3 h/day) produce a significant increase in citrate synthase activity (24.5 +/- 0.6 vs. 20.1 +/- 0.7 micromol x min(-1) x g(-1)), GLUT-4 content (22.9 +/- 0.8 vs. 17.4 +/- 0.4% GLUT-4 standard), and glycogen levels (54.3 +/- 9.4 vs. 28.6 +/- 9.4 micromol/g).
33	9124341	Maximally, insulin-stimulated glucose transport activity and cell surface GLUT-4 are increased by 55 (1.50 +/- 0.11 vs. 0.97 +/- 0.10 micromol x ml(-1) x 20 min(-1)) and 48% [12.0 +/- 0.8 vs. 8.1 +/- 0.9 disintegrations x min(-1) (dpm) x mg(-1)], respectively, in exercise-trained epitrochlearis muscles.
34	9124341	These results demonstrate that changes in insulin- and hypoxia-stimulated glucose transport activity after exercise training are fully accounted for by the appearance of cell surface GLUT-4 and support the concept of two intracellular pools of GLUT-4.
35	9216960	Percutaneous biopsy of vatus lateralis muscle was obtained in eight lean (L) and eight obese (O) nondiabetic subjects and in eight obese NIDDM subjects and was assayed for marker enzymes of the glycolytic [phosphofructokinase, glyceraldehyde phosphate dehydrogenase, hexokinase (HK)] and oxidative pathways [citrate synthase (CS), cytochrome-c oxidase], as well as for a glycogenolytic enzyme (glycogen phosphorylase) and a marker of anaerobic ATP resynthesis (creatine kinase).
36	9216960	Activity for glycolytic enzymes (phosphofructokinase, glyceraldehye phosphate dehydrogenase, HK) was highest in subjects with subjects with NIDDM, following the order of NIDDM > O > L, whereas maximum velocity for oxidative enzymes (CS, cytochrome-c oxidase) was lowest in subjects with NIDDM.
37	9546583	Twelve pairs of healthy sedentary males matched for their body mass index (BMI) with either a low insulin response (LIR; a stage of prediabetes) or a high (HIR; controls) to a standardized glucose infusion test (GIT) were studied in respect to their exercise capacities (W(OBLA), W(SL) and relative W(OBLA):W(OBLA) x W(SL)(-10 x 100), muscle fiber composition (%ST), muscle citrate synthase activity (CS), muscle ubiquinone (MUQ), MUQ over %ST (muscle quality index, MQI), and peripheral insulin sensitivity (PIS) as described with insulin-clamp techniques (SIGITmean).
38	9546583	LIR and HIR displayed normal PIS and positive relationships versus exercise capacity.
39	9648835	We tested the hypothesis that basal and insulin-stimulated expression of HK-II is decreased in NIDDM and obese subjects.
40	9648835	Skeletal muscle HK-I and HK-II activities were measured in seven lean and six obese normal subjects and eight patients with NIDDM before and at 3 and 5 h of a hyperinsulinemic (80 mU x m(-2) x min(-1)) euglycemic clamp.
41	9648835	To assess whether changes in HK-II expression seen during a glucose clamp are likely to be physiologically relevant, we also measured HK-I and HK-II activity in 10 lean normal subjects before and after a high-carbohydrate meal.
42	9648835	After an overnight fast, total HK, HK-I, and HK-II activities were similar in lean and obese control subjects; but HK-II was lower in NIDDM patients than in lean subjects (1.42 +/- 0.16 [SE] vs. 2.33 +/- 0.24 nmol x min(-1) x mg(-1) molecular weight, P < 0.05) and accounted for a lower proportion of total HK (33 +/- 3 vs. 47 +/- 3%, P < 0.025).
43	9648835	HK-II (but not HK-I) activity increased during the clamp in lean and obese subjects by 34 and 36% after 3 h and by 14 and 22% after 5 h of hyperinsulinemia; no increase was found in the NIDDM patients.
44	9648835	During the clamps, muscle HK-II activity correlated with muscle citrate synthase activity in the normal subjects (r = 0.58, P < 0.05) but not in the NIDDM patients.
45	9648835	In summary, NIDDM patients have lower muscle HK-II activity basally and do not increase the activity of this enzyme in response to a 5-h insulin stimulus.
46	9648835	In nondiabetic obese subjects, muscle HK-II expression and its regulation by insulin are normal.
47	10319590	The patients, 2 men and 5 women, showed common clinical features, characterized by isolated skeletal myopathy, high serum creatine kinase level, ragged-red fibers and cytochrome c oxidase-defective fibers.
48	10319590	Analysis of muscle biopsy specimens indicated that cytochrome c oxidase activity was decreased relative to that of citrate synthase in 5 of the 7 patients.
49	10480604	The FA-cultured islets also showed increased basal glucose usage and insulin secretion together with a lowered level of G-6-P and 50% reductions in citrate synthase Vmax and the citrate content.
50	10909963	Based on myosin heavy chain (MHC) expression, fibers were pooled into 3 groups (MHC I, MHC IIA, and MHC IIX), and the GLUT4 content of 15-40 pooled fibers was determined using SDS-PAGE and immunological detection.
51	10909963	Two weeks of exercise training increased (P < 0.05) the peak power output of the knee extensors by 13%, the maximal activities of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase by 21 and 18%, respectively, and the GLUT4 protein content by 26% in a muscle homogenate.
52	10971546	Enzyme activities (phosphofructokinase, 3-hydroxyacyl-CoA dehydrogenase, citrate synthase, lactate dehydrogenase and creatine kinase) and myoglobin content were assessed.
53	10971546	In conclusion, insulin treatment of patients with poorly controlled non-insulin-dependent diabetes mellitus increased the fast-twitch fibre area, reduced myoglobin levels and decreased muscle enzyme activity related to fatty acid oxidation.
54	11160042	Activation of the insulin receptor initiates signaling through both the phosphatidylinositol (PI) 3-kinase and the mitogen-activated protein kinase [MAPK, also referred to as extracellular signal-regulated kinases (ERK1/2)] pathways.
55	11160042	Acute exercise has no effect on the PI3-kinase pathway signaling elements but does activate the MAPK pathway, which may play a role in the adaptation of muscle to exercise.
56	11160042	It is unknown whether training produces a chronic effect on basal activity or insulin response of the MAPK pathway.
57	11160042	The present study was undertaken to determine whether exercise training improves the activity of the MAPK pathway or its response to insulin in obese Zucker rats, a well-characterized model of insulin resistance.
58	11160042	Compared with lean Zucker rats, untrained obese Zucker rats had reduced basal and insulin-stimulated activities of ERK2 and its downstream target p90 ribosomal S6 kinase (RSK2).
59	11160042	Seven weeks of training significantly increased basal and insulin-stimulated ERK2 and RSK2 activities, as well as insulin stimulation of MAPK kinase activity.
60	11160042	The training-induced increase in basal ERK2 activity was correlated with the increase in citrate synthase activity.
61	11160042	Therefore, 7 wk of training increases basal and insulin-stimulated ERK2 activity.
62	11473050	The remodeling was time dependent, with new small adipocytes appearing in clusters throughout the fat pad, and accompanied by a three- to fourfold increase in citrate synthase and fatty acid synthase activity.
63	11812754	Similar fiber type differences were found for carnitine palmitoyl transferase (CPT)-1, and a correlation was observed between ACBP and CPT-1.
64	11812754	Activities of CPT-1 and 3-hydroxy-acyl-CoA dehydrogenase were increased in muscles from obese rats, whereas citrate synthase activity was similar.
65	11812754	The 90% increase in the concentration of acyl-CoA in obese Zucker muscle compared with only a 30% increase in the concentration of ACBP supports the hypothesis that an increased concentration of free acyl-CoA is involved in the development of insulin resistance.
66	11912554	To examine the roles of carnitine-mediated transport and mitochondrial content, we also measured carnitine palmitoyltransferase I (CPT1), carnitine octanoyl transferase (COT), and citrate synthase (CS) activities.
67	11912554	CPT1 and CS activity were significantly (P <.05) higher (approximately 25%) in the endurance-trained subjects; there was no difference in COT activity.
68	12077722	Effects of streptozotocin-induced diabetes on markers of skeletal muscle metabolism and monocarboxylate transporter 1 to monocarboxylate transporter 4 transporters.
69	12077722	In various skeletal muscles of normal rats, monocarboxylate transporter 1 (MCT1) has been found to be highly correlated to lactate uptake, as well as to oxidative capacity, whereas the distribution and characteristics of MCT4 make it a good candidate for the extrusion of lactic acid from glycolytic muscle cells.
70	12077722	Since a previous study found decreased sarcolemmal lactate uptake in streptozotocin (STZ)-diabetic rats, we investigated the presence of MCT1 in relation to enzymatic markers of both oxidative and glycolytic pathways, as well as MCT4 content, in STZ-diabetic rats.
71	12077722	Soleus (SOL), red tibialis anterior (RTA), extensor digitorus longus (EDL), heart, and preparations of purified sarcolemmal vesicles (SV) from control and STZ-diabetic rats were harvested for MCT1 and MCT4 content, citrate synthase activity (CS), and lactate dehydrogenase (LDH) isozymes.
72	12077722	However, no change was found in either MCT1 or MCT4 content in these rats.
73	12077722	Regression analyses indicated (1) a strong relationship between LDH-4 and LDH-5 and (2) MCT1 was still correlated with CS activity in diabetic muscles.
74	12077722	These results suggest that diabetes-induced hyperlactatemia is not associated with changes in MCT1 or MCT4 expression, but with alterations of oxidative and glycolytic enzymes.
75	12098663	The activities of hexokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase (G6PDH), citrate synthase and phosphate-dependent glutaminase were determined.
76	12098663	The activities of hexokinase, G6PDH and citrate synthase were decreased by the diabetic state, whereas that of phosphofructokinase was raised.
77	12098663	The activities of hexokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase (G6PDH), citrate synthase and phosphate-dependent glutaminase were determined.
78	12098663	The activities of hexokinase, G6PDH and citrate synthase were decreased by the diabetic state, whereas that of phosphofructokinase was raised.
79	12145150	Insulin treatment also failed to stimulate muscle cytochrome C oxidase activity in the diabetic patients, although it modestly elevated citrate synthase.
80	12145150	Insulin treatments in subjects with type 2 diabetes had no effect on muscle mitochondrial protein synthesis and cytochrome C oxidase, a key enzyme for ATP production.
81	12351431	Creatine kinase and citrate synthase activities were measured as markers of myocyte and mitochondria content, respectively.
82	12351431	Activity of rotenone-sensitive NADH:O(2) oxidoreductase was normalized to creatine kinase activity, as was citrate synthase activity.
83	12351431	Also, citrate synthase activity was reduced in type 2 diabetic patients (lean 3.10 +/- 0.74, obese 3.24 +/- 0.82, type 2 diabetes 2.48 +/- 0.47 units/mU creatine kinase; P < 0.005).
84	12351431	Creatine kinase and citrate synthase activities were measured as markers of myocyte and mitochondria content, respectively.
85	12351431	Activity of rotenone-sensitive NADH:O(2) oxidoreductase was normalized to creatine kinase activity, as was citrate synthase activity.
86	12351431	Also, citrate synthase activity was reduced in type 2 diabetic patients (lean 3.10 +/- 0.74, obese 3.24 +/- 0.82, type 2 diabetes 2.48 +/- 0.47 units/mU creatine kinase; P < 0.005).
87	12351431	Creatine kinase and citrate synthase activities were measured as markers of myocyte and mitochondria content, respectively.
88	12351431	Activity of rotenone-sensitive NADH:O(2) oxidoreductase was normalized to creatine kinase activity, as was citrate synthase activity.
89	12351431	Also, citrate synthase activity was reduced in type 2 diabetic patients (lean 3.10 +/- 0.74, obese 3.24 +/- 0.82, type 2 diabetes 2.48 +/- 0.47 units/mU creatine kinase; P < 0.005).
90	12808136	Increased ATP production occurred in association with increased mRNA levels from both mitochondrial (NADH dehydrogenase subunit IV) and nuclear [cytochrome c oxidase (COX) subunit IV] genes (164-180%) encoding mitochondrial proteins (P < 0.05).
91	12808136	In addition, muscle mitochondrial protein synthesis, and COX and citrate synthase enzyme activities were increased by insulin (P < 0.05).
92	12882902	Exercise increased peak oxygen uptake (VO(2peak); 10%), activity of muscle mitochondrial enzymes (citrate synthase and cytochrome c oxidase, 45-76%) and mRNA levels of mitochondrial genes (COX4, ND4, both 66%) and genes involved in mitochondrial biogenesis (PGC-1alpha, 55%; NRF-1, 15%; TFAM, 85%).
93	12941774	Intramuscular heat shock protein 72 and heme oxygenase-1 mRNA are reduced in patients with type 2 diabetes: evidence that insulin resistance is associated with a disturbed antioxidant defense mechanism.
94	12941774	Muscle samples were obtained before and after the clamp and analyzed for heat shock protein (HSP)72 and heme oxygenase (HO)-1 mRNA, intramuscular triglyceride content, and the maximal activities of beta-hydroxyacyl-CoA dehydrogenase (beta-HAD) and citrate synthase (CS).
95	12941774	Basal expression of both HSP72 and HO-1 mRNA were lower (P < 0.05) by 33 and 55%, respectively, when comparing diabetic patients with age-matched and young control subjects, with no differences between the latter groups.
96	12941774	Both basal HSP72 (r = 0.75, P < 0.001) and HO-1 (r = 0.50, P < 0.05) mRNA expression correlated with the glucose infusion rate during the clamp.
97	14602787	Oxidative enzyme activities, fatty acid transporters (FAT/CD36 and FABPpm), and TG(m) were measured from basal muscle samples, and total LCACoA content was determined before and after insulin stimulation.
98	14602787	There was a significant relationship between the oxidative capacity of skeletal muscle and insulin sensitivity (citrate synthase, r = 0.71, P < 0.001; beta-hydroxyacyl CoA dehydrogenase, r = 0.61, P = 0.001).
99	15792355	The activities of key regulatory enzymes namely hexokinase (HK), phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS) and glucose-6 phosphate dehydrogenase (G6PD) have been monitored in the granulation tissues of normal and diabetic rats at different time points (2, 7, 14 and 21 days) of postwounding.
100	15883022	Monocarboxylate transporter (MCT) 1 and 4 content was measured in sarcolemmal vesicles and skeletal muscle.
101	15883022	Training increased citrate synthase activity in soleus and in red tibialis anterior, and improved insulin sensitivity measured by intraperitoneal glucose tolerance test.
102	15883022	Endurance training increased lactate influx in sarcolemmal vesicles at 1 mM of external lactate concentration and increased MCT1 expression on sarcolemmal vesicles.
103	15894466	Reduced insulin-mediated citrate synthase activity in cultured skeletal muscle cells from patients with type 2 diabetes: evidence for an intrinsic oxidative enzyme defect.
104	15894466	To determine the underlying mechanisms of these metabolic malfunctions, we studied mitochondrial respiration, uncoupled respiration and oxidative enzyme activities (citrate synthase (CS), 3-hydroxy-acyl-CoA-dehydrogenase activity (HAD)) before and after acute exposure to insulin and/or palmitate in myotubes established from healthy lean and obese subjects and T2D patients.
105	15894466	No differences were detected in mitochondrial respiration and HAD activity between myotubes from non-diabetic subjects and T2D patients, and none of these measures responded to high levels of insulin and/or palmitate.
106	15894466	Reduced insulin-mediated citrate synthase activity in cultured skeletal muscle cells from patients with type 2 diabetes: evidence for an intrinsic oxidative enzyme defect.
107	15894466	To determine the underlying mechanisms of these metabolic malfunctions, we studied mitochondrial respiration, uncoupled respiration and oxidative enzyme activities (citrate synthase (CS), 3-hydroxy-acyl-CoA-dehydrogenase activity (HAD)) before and after acute exposure to insulin and/or palmitate in myotubes established from healthy lean and obese subjects and T2D patients.
108	15894466	No differences were detected in mitochondrial respiration and HAD activity between myotubes from non-diabetic subjects and T2D patients, and none of these measures responded to high levels of insulin and/or palmitate.
109	16352671	In this study, we examined whether insulin-resistant obese Zucker rats have abnormalities in the AMPK pathway.
110	16352671	We compared AMPK and ACC phosphorylation and the protein content of the upstream AMPK kinase LKB1 and the AMPK-regulated transcriptional coactivator PPARgamma coactivator-1 (PGC-1) in gastrocnemius of sedentary obese Zucker rats and sedentary lean Zucker rats.
111	16352671	Protein expression of the AMPK kinase LKB1 was also reduced in the muscle from obese rats by 43%.
112	16352671	In obese rats, phosphorylation of ACC and protein expression of PGC-1alpha, two AMPK-regulated proteins, tended to be reduced by 50 (P = 0.07) and 35% (P = 0.1), respectively.
113	16352671	Furthermore, training also significantly increased LKB1 and PGC-1alpha protein content 2.8- and 2.5-fold, respectively, in the obese rats.
114	16352671	LKB1 protein strongly correlated with hexokinase II activity (r = 0.75, P = 0.001), citrate synthase activity (r = 0.54, P = 0.02), and PGC-1alpha protein content (r = 0.81, P < 0.001).
115	16352671	In summary, obese insulin-resistant rodents have abnormalities in the LKB1-AMPK-PGC-1 pathway in muscle, and these abnormalities can be restored by training.
116	16461555	The activities of hexokinase, glucose-6-phosphate dehydrogenase (G6PDH), phosphofructokinase (PFK), citrate synthase, phosphate-dependent glutaminase, NAD+-linked and NADP+-linked isocitrate dehydrogenase were assayed.
117	16461555	The activities of G6PDH and glutaminase were decreased, whereas that of PFK was raised by the diabetic state.
118	16814734	Individuals with a family history of type 2 diabetes display skeletal muscle insulin resistance and mitochondrial dysfunction; adiponectin levels strongly correlate with mtDNA content.
119	16814734	Knockout of the adiponectin gene in mice is associated with insulin resistance and low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle.
120	16814734	Adiponectin treatment of human myotubes in primary culture induces mitochondrial biogenesis, palmitate oxidation, and citrate synthase activity, and reduces the production of reactive oxygen species.
121	17095651	Testing included 90 min of cycle ergometry at 60% Vo(2 peak) with preexercise muscle biopsies analyzed for IMCL and mitochondrial size/area using electron microscopy and short-chain beta-hydroxyacyl-CoA dehydrogenase (SCHAD) and citrate synthase (CS) enzyme activity.
122	17130474	A total of 13 type 2 diabetic and 17 nondiabetic subjects were studied on two separate occasions while maintaining similar insulin and glucose levels in both groups by 7-h infusions of somatostatin, low- or high-dose insulin (0.25 and 1.5 mU/kg of fat-free mass per min, respectively), and glucose.
123	17130474	The lack of MAPR increment in response to high-dose insulin in type 2 diabetic patients occurred in association with reduced glucose disposal and expression of peroxisome proliferator-activated receptor-gamma coactivator 1alpha, citrate synthase, and cytochrome c oxidase I.
124	17327447	Microarray and real-time PCR studies identified a set of metabolically relevant genes influenced by KPF including peroxisome proliferator-activated receptor gamma coactivator-1alpha, carnitine palmitoyl transferase-1, mitochondrial transcription factor 1, citrate synthase, and uncoupling protein-3, although KPF itself is not a direct mitochondrial uncoupler.
125	17351150	Muscle biopsies obtained from 10 obese type 2 diabetic and 8 obese nondiabetic male subjects were used for assessment of 3-hydroxy-Acyl-CoA-dehydrogenase (HAD) and citrate synthase activity, uncoupling protein (UCP)3 content, oxidative stress measured as 4-hydroxy-2-nonenal (HNE), fiber type distribution, and respiration in isolated mitochondria.
126	17351150	There were no differences in respiration with palmitoyl-l-carnitine plus malate, citrate synthase activity, HAD activity, UCP3 content, or oxidative stress measured as HNE between the groups.
127	17351150	Muscle biopsies obtained from 10 obese type 2 diabetic and 8 obese nondiabetic male subjects were used for assessment of 3-hydroxy-Acyl-CoA-dehydrogenase (HAD) and citrate synthase activity, uncoupling protein (UCP)3 content, oxidative stress measured as 4-hydroxy-2-nonenal (HNE), fiber type distribution, and respiration in isolated mitochondria.
128	17351150	There were no differences in respiration with palmitoyl-l-carnitine plus malate, citrate synthase activity, HAD activity, UCP3 content, or oxidative stress measured as HNE between the groups.
129	17374701	HF-fed ZDF rats developed hyperglycemia (mean: 24.4 +/- 2.1 mM), impairments in muscle insulin-stimulated glucose transport, increases in the FA transporter FAT/CD36, and increases in total ceramide and DAG content.
130	17374701	Interestingly, improvements in insulin-stimulated glucose transport and increased GLUT4 transporter expression in isolated muscle were seen only in conditions that included exercise training.
131	17374701	However, exercise did induce modest increases in peroxisome proliferator-activated receptor-gamma coactivator-1alpha, citrate synthase, and beta-hydroxyacyl-CoA dehydrogenase activity.
132	17374701	Thus reduction of skeletal muscle FAT/CD36 and content of ceramide and DAG may be important mechanisms by which exercise training blunts the progression of diet-induced insulin resistance in skeletal muscle.
133	17418099	Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) stimulated mitochondrial gene expression program in control cells, but not in the ERRalpha null cells.
134	17418099	Interestingly, the induction of levels of mitochondrial oxidative stress protection genes in response to increased PGC-1alpha levels was dependent on ERRalpha.
135	17418099	Furthermore, we found that the PGC-1alpha-mediated induction of estrogen-related receptor gamma and nuclear respiratory factor 2 (NRF-2), was dependent on the presence of ERRalpha.
136	17418099	Basal levels of NRF-2 were decreased in the absence of ERRalpha.
137	17418099	The absence of ERRalpha resulted in a decrease in citrate synthase enzyme activity in response to PGC-1alpha overexpression.
138	17513699	To determine whether AMPK is involved in concomitant metabolic adaptations to training, we measured markers of mitochondria (citrate synthase and succinate dehydrogenase) and glucose uptake capacity (GLUT4 and hexokinase II).
139	17519422	Several markers of muscle mitochondrial fatty acid oxidative capacity were measured, including (14)C-palmitate oxidation, palmitoyl-CoA oxidation in isolated mitochondria, oxidative enzyme activity (citrate synthase, beta-hydroxyacyl CoA dehydrogenase, medium-chain acyl-CoA dehydrogenase, and carnitine palmitoyl-transferase 1), and expression of proteins involved in mitochondrial metabolism.
140	17519422	Furthermore, oxidative enzyme activity and protein expression of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha, uncoupling protein (UCP) 3, and mitochondrial respiratory chain subunits were significantly elevated in fat-fed animals.
141	17519422	A similar pattern was present in muscle of fat-fed rats, obese Zucker rats, and db/db mice, with increases observed for oxidative enzyme activity and expression of PGC-1alpha, UCP3, and subunits of the mitochondrial respiratory chain.
142	17890427	Despite the global lack of effect of rosiglitazone-mediated insulin sensitization on skeletal muscle mitochondria, subjects with the most preserved functional capacity demonstrated some plasticity in their mitochondria biology as evidenced by an upregulation of electron transfer chain proteins and in citrate synthase activity.
143	18984854	Several new hypotheses were generated by these data, including mechanisms of net cytosolic protein oxidation, formaldehyde generation by the methionine cycle, and inhibition of carbon substrate oxidation via reduction in citrate synthase and short-chain acyl-CoA dehydrogenase.
144	19246652	Intramyocellular lipid increased in STZ (122.9 +/- 3.6% of control) but not Ins2(Akita+/-) likely resultant from depressed citrate synthase (control: 6.2 +/- 1.2 micromol.s(-1).mg(-1); Ins2(Akita+/-): 5.2 +/- 0.8 micromol.s(-1).mg(-1); STZ: 2.8 +/- 0.5 micromol.s(-1).mg(-1)) and 3-beta-hydroxyacyl coenzyme-A dehydrogenase (control: 4.2 +/- 0.6 nmol.s(-1).mg(-1); Ins2(Akita+/-): 5.0 +/- 0.6 nmol.s(-1).mg(-1); STZ: 2.7 +/- 0.6 nmol.s(-1).mg(-1)) enzyme activity in STZ muscle.
145	19793954	Apelin, is a recently identified adipokine that when given to mice results in increases in skeletal muscle uncoupling protein 3 (UCP3) content.
146	19793954	Similarly, acute apelin treatment has been shown to increase the activity of 5'-AMP-activated protein kinase (AMPK), a reputed mediator of skeletal muscle mitochondrial biogenesis.
147	19793954	We made the novel observation that the activities of citrate synthase, cytochrome c oxidase, and beta-hydroxyacyl coA dehydrogenase (betaHAD) were increased in triceps but not heart and soleus muscles from apelin-treated rats.
148	19793954	The increases in mitochondrial marker proteins were associated with increases in proliferator-activated receptor-gamma coactivator-1 (PGC-1beta) but not PGC-1alpha or Pgc-1-related co-activator (PRC) mRNA expression.
149	19793954	Chronic and acute apelin treatment did not increase the protein content and/or phosphorylation status of AMPK and its downstream substrate acetyl-CoA carboxylase.
150	19793954	Given the lack of an effect of apelin on AMPK signaling and PGC-1alpha mRNA expression, these results suggest that apelin increases skeletal muscle mitochondrial content through a mechanism that is distinct from that of more robust physiological stressors.
151	20616029	Here we demonstrate that FGF21 regulates energy homeostasis in adipocytes through activation of AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1), resulting in enhanced mitochondrial oxidative function.
152	20616029	AMPK phosphorylation levels were increased by FGF21 treatment in adipocytes as well as in white adipose tissue from ob/ob mice.
153	20616029	FGF21 treatment increased cellular NAD(+) levels, leading to activation of SIRT1 and deacetylation of its downstream targets, peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) and histone 3.
154	20616029	Activation of AMPK and SIRT1 by FGF21 in adipocytes enhanced mitochondrial oxidative capacity as demonstrated by increases in oxygen consumption, citrate synthase activity, and induction of key metabolic genes.
155	20616029	The effects of FGF21 on mitochondrial function require serine/threonine kinase 11 (STK11/LKB1), which activates AMPK.
156	20616029	Inhibition of AMPK, SIRT1, and PGC-1alpha activities attenuated the effects of FGF21 on oxygen consumption and gene expression, indicating that FGF21 regulates mitochondrial activity and enhances oxidative capacity through an AMPK-SIRT1-PGC1alpha-dependent mechanism in adipocytes.
157	21078391	In each group of cells, enzyme activities such as glucose-6-phosphate (G6PDH) and glycerol-3-phosphate dehydrogenases (G3PDH), lactate/pyruvate, glycogen levels and citrate synthase were measured as an index of glycolytic dysregulation and mitochondrial mass, respectively.
158	21078391	In comparison with N and NL, D cells presented higher G6PDH and cytoplasmic G3PDH activities, lactate/pyruvate, glycogen content but similar levels of citrate synthase, and decay time of contraction.
159	21078391	In each group of cells, enzyme activities such as glucose-6-phosphate (G6PDH) and glycerol-3-phosphate dehydrogenases (G3PDH), lactate/pyruvate, glycogen levels and citrate synthase were measured as an index of glycolytic dysregulation and mitochondrial mass, respectively.
160	21078391	In comparison with N and NL, D cells presented higher G6PDH and cytoplasmic G3PDH activities, lactate/pyruvate, glycogen content but similar levels of citrate synthase, and decay time of contraction.
161	21088877	Wistar rats received one single injection of alloxan (250 mg/kg) and after 15 days we evaluated mitochondrial respiratory chain complexes I, II, II-III and IV, creatine kinase and citrate synthase activities in prefrontal cortex, hippocampus and striatum.
162	21088877	Moreover, diabetes rats decreased creatine kinase activity in striatum and increased citrate synthase activity in hippocampus.
163	21088877	Wistar rats received one single injection of alloxan (250 mg/kg) and after 15 days we evaluated mitochondrial respiratory chain complexes I, II, II-III and IV, creatine kinase and citrate synthase activities in prefrontal cortex, hippocampus and striatum.
164	21088877	Moreover, diabetes rats decreased creatine kinase activity in striatum and increased citrate synthase activity in hippocampus.
165	22178940	When β-cells were incubated under these conditions, the expression levels of mitochondrial electron transport chain complex subunits, mitochondrial antioxidant enzymes (such as MnSOD and Prx3), β-cell apoptosis, lipogenic enzymes (such as ACC, FAS and ABCA1), intracellular lipid accumulation, oxidative stress, ER stress, mitochondrial membrane depolarization, nuclear NF- κB and sterol regulatory element binding protein 1c (SREBP1c) were all increased, in parallel with decreases in intracellular ATP content, citrate synthase enzymatic activity and glucose-stimulated insulin secretion.
166	22355328	Glucose intolerance (iAUC increased by ∼60%) and blunted insulin-stimulated hepatic Akt and GSK3β phosphorylation (∼40-60%) were found in both feeding conditions (p<0.01 vs Con, assessed after 1 week).
167	22355328	No impairment of mitochondrial function was found (oxidation capacity, expression of PGC1α, CPT1, respiratory complexes, enzymatic activity of citrate synthase & β-HAD).
168	22355328	Interestingly, associated with the upregulated lipogenic enzymes (ACC, FAS and SCD1), two (PERK/eIF2α and IRE1/XBP1) of three ER stress pathways were significantly activated in HFru-fed mice.
169	22485150	Regulation of expression of citrate synthase by the retinoic acid receptor-related orphan receptor α (RORα).
170	23460046	Impaired mitochondrial biogenesis due to dysfunctional adiponectin-AMPK-PGC-1α signaling contributing to increased vulnerability in diabetic heart.
171	23460046	Whether adiponectin (APN), a potent cardioprotective molecule, regulates cardiac mitochondrial function has also not been previously investigated.
172	23460046	Moreover, mitochondrial biogenesis of ob/ob cardiomyocytes is significantly impaired, as evidenced by reduced Ppargc-1a/Nrf-1/Tfam mRNA levels, mitochondrial DNA content, ATP content, citrate synthase activity, complexes I/III/V activity, AMPK phosphorylation, and increased PGC-1α acetylation.
173	23460046	Since APN is an upstream activator of AMPK and APN plasma levels are significantly reduced in ob/ob mice, we further tested the hypothesis that reduced APN in ob/ob mice is causatively related to mitochondrial biogenesis impairment.
174	23523698	Erythropoietin contributes to slow oxidative muscle fiber specification via PGC-1α and AMPK activation.
175	23523698	In vitro erythropoietin treatment of primary skeletal myoblasts increased mitochondrial biogenesis gene expression including PGC-1α by 2.6-fold, CytC by 2-fold, oxygen consumption rate by 2-fold, and citrate synthase activity by 58%.
176	23523698	Erythropoietin also increases AMPK, which induces PGC-1α and stimulates slow oxidative fiber formation.
177	23523698	These data suggest that erythropoietin contributes to skeletal muscle fiber programming and metabolism, and increases PGC-1α and AMPK activity during muscle development directly to affect the proportion of slow/fast twitch myofibers in mature skeletal muscle.