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Publication : C1q/TNF-related protein 2 (CTRP2) deletion promotes adipose tissue lipolysis and hepatic triglyceride secretion.

First Author  Lei X Year  2019
Journal  J Biol Chem Volume  294
Issue  43 Pages  15638-15649
PubMed ID  31439668 Mgi Jnum  J:282612
Mgi Id  MGI:6383337 Doi  10.1074/jbc.RA119.009230
Citation  Lei X, et al. (2019) C1q/TNF-related protein 2 (CTRP2) deletion promotes adipose tissue lipolysis and hepatic triglyceride secretion. J Biol Chem 294(43):15638-15649
abstractText  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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