Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.4.1.2 (acetyl-CoA carboxylase)
 2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of high-fat ethanol-containing food. Delivery of recombinant adiponectin into these mice dramatically alleviated hepatomegaly and steatosis (fatty liver) and also significantly attenuated inflammation and the elevated levels of serum alanine aminotransferase. These therapeutic effects resulted partly from the ability of adiponectin to increase carnitine palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while it decreased the activities of two key enzymes involved in fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase. Furthermore, adiponectin treatment could suppress the hepatic production of TNF-alpha and plasma concentrations of this proinflammatory cytokine. Adiponectin was also effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice. These results demonstrate a novel mechanism of adiponectin action and suggest a potential clinical application of adiponectin and its agonists in the treatment of liver diseases.
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PMID:The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. 1284 63

Biochemical, genetic, and animal studies in recent years have established a critical role for the adipokine Acrp30/adiponectin in controlling whole-body metabolism, particularly by enhancing insulin sensitivity in muscle and liver, and by increasing fatty acid oxidation in muscle. We describe a widely expressed and highly conserved family of adiponectin paralogs designated as C1q/tumor necrosis factor-alpha-related proteins (CTRPs) 1-7. In the present study, we focus on mCTRP2, the mouse paralog most similar to adiponectin. At nanomolar concentrations, bacterially produced mCTRP2 rapidly induced phosphorylation of AMP-activated protein kinase, acetyl-CoA carboxylase, and mitogen-activated protein kinase in C2C12 myotubes, which resulted in increased glycogen accumulation and fatty acid oxidation. The discovery of a family of adiponectin paralogs has implications for understanding the control of energy homeostasis and could provide new targets for pharmacologic intervention in metabolic diseases such as diabetes and obesity.
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PMID:A family of Acrp30/adiponectin structural and functional paralogs. 1523 94

Adiponectin is an adipocyte-derived hormone that has a number of metabolic effects in the body, including the control of both glucose and fatty acid metabolism. The globular head domain of adiponectin, gAd, has also been shown to increase fatty acid oxidation in skeletal muscle. Within days after birth, a rapid increase in fatty acid oxidation occurs in the heart. We examined whether adiponectin or gAd plays a role in this maturation of cardiac fatty acid oxidation. Plasma adiponectin increased in newborn rabbits following birth: 1.2 +/- 0.3 microg/ml in 1-day-old, 6.8 +/- 1.8 microg/ml in 7-day-old, and 45 +/- 5 microg/ml in 6-week-old rabbits. Because plasma insulin levels decrease and remain low throughout the suckling period, and because this decrease may contribute to the maturation of fatty acid oxidation, we examined the effects of adiponectin and gAd on fatty acid oxidation in isolated perfused 1-day-old rabbit hearts in the presence or absence of 100 microunits/ml insulin. Adiponectin (10 microg/ml) did not alter fatty acid oxidation in the presence of insulin. In the absence of insulin, the addition of recombinant gAd (1.5 microg/ml) increased fatty acid oxidation compared with control (129 +/- 18 versus 66 +/- 11 nmol.g dry weight(-1).min(-1), respectively (p < 0.05). In 7-day-old hearts, where fatty acid oxidation rates were 5-fold higher than 1-day-old hearts, gAd did not alter fatty acid oxidation rates. The increase in fatty acid oxidation in 1-day-old hearts occurred independently of changes in 5'-AMP-activated protein kinase, acetyl-CoA carboxylase, or malonyl-CoA. The effect of gAd on fatty acid oxidation was reversed in the presence of 100 microunits/ml insulin. These results suggest that a decrease in plasma insulin and increase in gAd are involved in the increase of cardiac fatty acid oxidation in the immediate newborn period.
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PMID:gAd-globular head domain of adiponectin increases fatty acid oxidation in newborn rabbit hearts. 1526 15

Several adipocyte-secreted factors have been demonstrated to potentially link obesity, insulin resistance, and cardiovascular disease. Among those, adiponectin is an insulin-sensitizing and anti-inflammatory adipokine, concentrations of which are decreased in obesity-associated metabolic and vascular disorders. Recently, two adiponectin receptors (AdipoR) have been isolated and adenosine monophosphate kinase (AMPK), as well as acetyl coenzyme A carboxylase (ACC), appear to be critical downstream mediators for various effects of this adipokine. In addition to beneficial metabolic effects, adiponectin seems to be vasoprotective by interfering with various atherogenic processes. Of clinical interest, thiazolidinediones (TZDs) which are used in the treatment of type 2 diabetes stimulate adiponectin expression and secretion whereas several hormones dysregulated in insulin resistance and obesity downregulate this adipokine. The current knowledge on regulation and function of adiponectin in obesity, insulin resistance, and cardiovascular disease is summarized in this review and its clinical implications are discussed.
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PMID:Adiponectin, obesity, and cardiovascular disease. 1558 86

Polyunsaturated fatty acids (PUFA) and a number of drugs (metformin, thiazolidinediones) and hormones (leptin, adiponectin) that activate AMP-activated protein kinase (AMPK) have been reported to improve insulin sensitivity. To determine whether PUFA activate AMPK, Sprague-Dawley rats were adapted to a 3h meal-feeding regimen using a fat-free diet (FFD) supplemented with fish oil (n-3) or triolein (n-9) for 7 days. No differences in hepatic AMPK activity were observed between the groups after 21h of fasting. On the other hand, hepatic AMPK phosphorylation was decreased in rats refed the FFD, the FFD+triolein, and the FFD+PUFA by 80%, 75%, and 50%, respectively, when assessed 2h after completion of a meal. In keeping with these changes, decreases in acetyl-CoA carboxylase phosphorylation and carnitine palmitoyl transferase-1 mRNA and increases in fatty acid synthase gene expression were greatest in rats fed the FFD and least in the PUFA-fed rats. The results indicate that dietary PUFA enhance hepatic AMPK activity in vivo, and implicate AMPK as a component of the nutrient-sensing mechanism through which dietary fatty acids and especially PUFA influence the regulation of hepatic lipid metabolism and gene expression.
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PMID:Dietary polyunsaturated fatty acids enhance hepatic AMP-activated protein kinase activity in rats. 1560 47

Adiponectin has been shown to regulate glucose and fatty acid uptake and metabolism in skeletal muscle. Here we investigated the role of the recently cloned adiponectin receptor (AdipoR) isoforms in mediating effects of both globular (gAd) and full-length (fAd) adiponectin, and their regulation by hyperglycemia (25 mM, 20 h) and hyperinsulinemia (100 nM, 20 h). We used L6 rat skeletal muscle cells, which were found to express both AdipoR1 and AdipoR2 mRNA in a ratio of over 6:1 respectively. Hyperglycemia and hyperinsulinemia both decreased AdipoR1 receptor expression by approximately 50%, while the latter induced an increase of approximately threefold in AdipoR2 expression. The ability of gAd to increase GLUT4 myc translocation, glucose uptake, fatty acid uptake and oxidation, as well as AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, was decreased by both hyperglycemia and hyperinsulinemia. Interestingly, hyperinsulinemia induced the ability of fAd to elicit fatty acid uptake and enhanced fatty acid oxidation in response to fAd. In summary, our results suggest that both hyperglycemia and hyperinsulinemia cause gAd resistance in rat skeletal muscle cells. However, hyperinsulinemia induces a switch toward increased fAd sensitivity in these cells.
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PMID:Hyperglycemia- and hyperinsulinemia-induced alteration of adiponectin receptor expression and adiponectin effects in L6 myoblasts. 1632 33

Adiponectin, an adipocyte-derived polypeptide hormone, plays an important role in regulating fatty acid oxidation. beta-oxidation of fatty acids supplies most of the cardiac energy and carnitine palmitoyltransferase (CPT)-1 serves as a key regulator during this process. To characterize the potential effects of adiponectin on CPT-1, we incubated rat neonatal cardiomyocytes with globular adiponectin (gAd). Results showed that gAd promoted the activity and mRNA expression of CPT-1. The underlying signal pathway involved in this modulatory effect was further investigated. Inhibition of AMP-activated protein kinase (AMPK) with adenine 9-beta-d-arabinofuranoside (AraA) completely abrogated gAd-mediated AMPK and acetyl coenzyme A carboxylase (ACC) phosphorylation and suppressed the promotion of CPT-1 activity. gAd also induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and peroxisome proliferator-activated receptor (PPAR)-alpha, which was inhibited by AraA. SB202190, a p38MAPK inhibitor, blocked gAd-stimulated PPAR-alpha phosphorylation. When AMPK and/or p38MAPK was inhibited, gAd-enhanced mRNA expression of CPT-1 was partially reduced. In conclusion, our study suggests that the activation of AMPK signaling cascade participates in the promotion effect of gAd on CPT-1.
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PMID:Adiponectin modulates carnitine palmitoyltransferase-1 through AMPK signaling cascade in rat cardiomyocytes. 1710 77

This study investigated the effect of N-acetylcysteine on plasma adiponectin, renal adiponectin receptors, lipid metabolism and oxidative stress in streptozotocin-induced diabetic rats. Metabolic parameters, plasma adiponectin level, renal protein expression of adiponectin receptors were analyzed in controls and diabetic rats treated with or without N-acetylcysteine in drinking water for 8 weeks. Plasma lipid, creatinine and free 5-F(2t)-isoprostane levels, urine protein excretion rate, mesangial matrix expansion index, and protein expression of renal connective tissue growth factor (CTGF) were increased in diabetic rats. The decreased plasma adiponectin levels and renal protein expression of adiponectin receptor 1 were accompanied by the decreased renal phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK)-alpha (Thr172) and protein expression of phospho-acetyl coenzyme A carboxylase (ACC) (Ser79) which led to the increased renal triglyceride levels in diabetic rats. There was no difference in the protein expression of renal adiponectin receptor 2 between control and diabetic rats. N-acetylcysteine treatment attenuated the increased oxidative stress, plasma and renal lipids, urine protein excretion rate, mesangial matrix expansion index, and protein expression of renal CTGF, but did not affect plasma adiponectin levels, renal protein expression of adiponectin receptor 1, phosphorylation of AMPK-alpha (Thr172) and renal protein expression of phospho-ACC (Ser79) in diabetic rats. These results suggested that the decreased plasma adiponectin and renal adiponectin receptor 1 result in the increased renal triglyceride that stimulates renal CTGF expression leading to the renal hypertrophy and the deteriorated renal function in the diabetic rats. N-acetylcysteine treatment attenuates the increased oxidative stress, but has no effect on the decreased plasma adiponectin and renal adiponectin receptor 1 in diabetic rats, indicating that oxidative stress may not contribute to the decreased plasma adiponectin and renal adiponectin receptor 1 protein expression in diabetic rats.
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PMID:Effect of N-acetylcysteine on plasma adiponectin and renal adiponectin receptors in streptozotocin-induced diabetic rats. 1727 Jan 71

Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), and adiponectin increases glucose uptake. The aim of this study was to determine whether AICAR stimulates muscle glucose uptake in humans. We studied 29 healthy men (aged 26 +/- 8 years, BMI 25 +/- 4 kg/m(2) [mean +/- SD]). Rates of muscle 2-deoxyglucose (2DG) uptake were determined by measuring accumulation of total muscle 2DG (2DG and 2DG-6-phosphate) during a primed, continuous 2DG infusion. The effects of AICAR and exercise on muscle AMPK activity/phosphorylation and 2DG uptake were determined. Whole-body glucose disposal was compared before and during AICAR with the euglycemic-hyperinsulinemic clamp. Muscle 2DG uptake was linear over 9 h (R(2) = 0.88 +/- 0.09). After 3 h, 2DG uptake increased 2.1 +/- 0.8- and 4.7 +/- 1.7-fold in response to AICAR or bicycle exercise, respectively. AMPK alpha(1) and alpha(2) activity or AMPK phosphorylation was unchanged after 20 min or 3 h of AICAR, but AMPK phosphorylation significantly increased immediately and 3 h after bicycle exercise. AICAR significantly increased phosphorylation of extracellular signal-regulated kinase 1/2, but phosphorylation of beta-acetyl-CoA carboxylase, glycogen synthase, and protein kinase B or insulin receptor substrate-1 level was unchanged. Mean whole-body glucose disposal increased by 7% with AICAR from 9.3 +/- 0.6 to 10 +/- 0.6 mg x kg(-1) x min(-1) (P < 0.05). In healthy people, AICAR acutely stimulates muscle 2DG uptake with a minor effect on whole-body glucose disposal.
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PMID:5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. 1751 6

Adiponectin can improve both glucose metabolism and insulin resistance via the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Activated AMPK phosphorylates a variety of intracellular proteins, including acetyl coenzyme A carboxylase (ACC) that is involved in fatty acid oxidation. Adenosine monophosphate-activated protein kinase increases glucose transport by stimulating the translocation of glucose transporter 4 (GLUT4) to the sarcolemma in the heart. Adiponectin exerts its effect through adiponectin receptors, which are predominantly expressed in the liver and skeletal muscle. It is unknown whether the cardiac expression of adiponectin and its receptors is changed in diabetic rats. In the present study, we investigated the protein expression of adiponectin and its receptors in streptozotocin (STZ)-induced diabetic rat hearts. We also explored whether the levels of AMPK, ACC, and GLUT4 will be altered with the changed adiponectin and its receptors in STZ diabetic rat hearts. Plasma and cardiac adiponectin levels were measured by radioimmunoassay. Plasma and cardiac interleukin 6 and plasma tumor necrosis factor alpha (TNF-alpha) were assayed by enzyme-linked immunosorbent assay. Cardiac adiponectin receptors, AMPK-alpha, ACC, GLUT4, and TNF-alpha were analyzed by Western blot in control and STZ diabetic rats. The plasma adiponectin level was decreased, but the cardiac protein expression of adiponectin receptor 1 was increased in diabetic rats. There was no difference in the cardiac adiponectin level and the cardiac adiponectin receptor 2 protein expression between control and diabetic rats. The phosphorylation of AMPK-alpha and protein expression of GLUT4 were decreased, but the phosphorylation of ACC was unchanged in diabetic rat hearts. Plasma and cardiac levels of interleukin 6 and TNF-alpha were increased in diabetic rats. In conclusion, STZ-induced diabetes up-regulates adiponectin receptors in the heart. Despite an increase in cardiac adiponectin receptor 1 expression, there is an increased cardiac inflammatory response and a decreased GLUT4 protein expression associated with a reduction in circulating adiponectin.
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PMID:Cardiac expression of adiponectin and its receptors in streptozotocin-induced diabetic rats. 1788 46


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