Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CTRP2 is a secreted plasma protein of the C1q family that enhances glycogen deposition and fat oxidation in cultured myotubes. Its in vivo metabolic function, however, has not been established. We show here that acute and chronic metabolic perturbations induced by fasting or high-fat feeding up-regulated the mRNA expression of Ctrp2 in white adipose tissue without affecting its circulating plasma levels. We generated a transgenic mouse model with elevated circulating levels of CTRP2 to determine its metabolic function in vivo. When fed a low-fat diet, wild-type and CTRP2 transgenic mice exhibited no metabolic phenotypes. When challenged with a high-fat diet to induce obesity, wild-type and CTRP2 transgenic mice had similar weight gain, adiposity, food intake, metabolic rate, and energy expenditure. Fasting serum lipid and adipokine profiles were also similar between the two groups of mice. However, while glucose and insulin levels in the fasted state were comparable between wild-type and CTRP2 transgenic mice, insulin levels in the fed state were consistently lower in transgenic mice. Notably, CTRP2 transgenic mice had improved insulin tolerance and a greater capacity to handle acute lipid challenge relative to littermate controls. Our results highlight, for the first time, the in vivo role of CTRP2 in modulating whole-body metabolism.
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PMID:CTRP2 overexpression improves insulin and lipid tolerance in diet-induced obese mice. 2458 39

The highly conserved C1q/TNF-related protein (CTRP) family of secreted hormones has emerged as important regulators of insulin action and of sugar and fat metabolisms. Among these, the specific biological function of CTRP2 remains elusive. Here, we show that the expression of human CTRP2 is positively correlated with body mass index (BMI) and is up-regulated in obesity. We used a knockout (KO) mouse model to determine CTRP2 function and found that Ctrp2-KO mice have significantly elevated metabolic rates and energy expenditure leading to lower body weights and lower adiposity. CTRP2 deficiency up-regulated the expression of lipolytic enzymes and protein kinase A signaling, resulting in enhanced adipose tissue lipolysis. In cultured adipocytes, CTRP2 treatment suppressed triglyceride (TG) hydrolysis, and its deficiency enhanced agonist-induced lipolysis in vivo CTRP2-deficient mice also had altered hepatic and plasma lipid profiles. Liver size and hepatic TG content were significantly reduced, but plasma TG was elevated in KO mice. Both plasma and hepatic cholesterol levels, however, were reduced in KO mice. Loss of CTRP2 also enhanced hepatic TG secretion and contributed to impaired plasma lipid clearance following an oral lipid gavage. Liver metabolomic analysis revealed significant changes in diacylglycerols and phospholipids, suggesting that increased membrane remodeling may underlie the altered hepatic TG secretion we observed. Our results provide the first in vivo evidence that CTRP2 regulates lipid metabolism in adipose tissue and liver.
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PMID:C1q/TNF-related protein 2 (CTRP2) deletion promotes adipose tissue lipolysis and hepatic triglyceride secretion. 3143 68