Partial Deficiency of CTRP12 Alters Hepatic Lipid Metabolism

Physiol Genomics. 2016 Dec 1;48(12):936-949. doi: 10.1152/physiolgenomics.00111.2016. Epub 2016 Nov 4.

Abstract

Secreted hormones play pivotal roles in tissue cross talk to maintain physiologic blood glucose and lipid levels. We previously showed that C1q/TNF-related protein 12 (CTRP12) is a novel secreted protein involved in regulating glucose metabolism whose circulating levels are reduced in obese and insulin-resistant mouse models. Its role in lipid metabolism, however, is unknown. Using a novel heterozygous mouse model, we show that the loss of a single copy of the Ctrp12 gene (also known as Fam132a and adipolin) affects whole body lipid metabolism. In Ctrp12 (+/-) male mice fed a control low-fat diet, hepatic fat oxidation was upregulated while hepatic VLDL-triglyceride secretion was reduced relative to wild-type (WT) littermates. When challenged with a high-fat diet, Ctrp12 (+/-) male mice had impaired lipid clearance in response to acute lipid gavage, reduced hepatic triglyceride secretion, and greater steatosis with higher liver triglyceride and cholesterol levels. Unlike male mice, Ctrp12 (+/-) female mice fed a control low-fat diet were indistinguishable from WT littermates. When obesity was induced by high-fat feeding, Ctrp12 (+/-) female mice developed mild insulin resistance with impaired insulin tolerance. In contrast to male mice, hepatic triglyceride secretion was increased in Ctrp12 (+/-) female mice fed a high-fat diet. Thus, in different dietary and metabolic contexts, loss of a single Ctrp12 allele affects glucose and lipid metabolism in a sex-dependent manner, highlighting the importance of genetic and environmental determinants of metabolic phenotypes.

Keywords: adipokine; diabetes; lipid metabolism; obesity; triglyceride secretion.

MeSH terms

  • Adipokines / metabolism*
  • Animals
  • Blood Glucose / metabolism
  • Diet, High-Fat / methods
  • Female
  • Glucose / metabolism
  • Insulin / metabolism
  • Insulin Resistance / physiology
  • Lipid Metabolism / physiology*
  • Lipoproteins, VLDL / metabolism
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / metabolism
  • Triglycerides / metabolism
  • Up-Regulation / physiology

Substances

  • Adipokines
  • Blood Glucose
  • C1qtnf12 protein, mouse
  • Insulin
  • Lipoproteins, VLDL
  • Triglycerides
  • very low density lipoprotein triglyceride
  • Glucose