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

J Biol Chem. 2019 Oct 25;294(43):15638-15649. doi: 10.1074/jbc.RA119.009230. Epub 2019 Aug 22.


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.

Keywords: C1q family; C1q/TNF-related protein; CTRP; adipocyte biology; adipokine; adipose tissue; dyslipidemia; endocrine metabolism; hepatic triglyceride secretion; lipid metabolism; lipolysis; liver metabolism; obesity; secreted protein.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3T3-L1 Cells
  • Adipose Tissue / metabolism*
  • Adiposity
  • Animals
  • Body Weight
  • Cholesterol / blood
  • Complement System Proteins / metabolism*
  • Diet, High-Fat
  • Energy Metabolism
  • Gene Deletion*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Lipolysis*
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Obesity / metabolism
  • Triglycerides / blood
  • Triglycerides / metabolism*
  • Up-Regulation / genetics


  • C1QTNF2 protein, human
  • CTRP2 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Triglycerides
  • Complement System Proteins
  • Cholesterol