Partial deficiency of CTRP12 alters hepatic lipid metabolism

Stefanie Y. Tan, Hannah C. Little, Xia Lei, Shuoyang Li, Susana Rodriguez, G. William Wong

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)936-949
Number of pages14
JournalPhysiological Genomics
Volume48
Issue number12
DOIs
StatePublished - Dec 19 2016

Keywords

  • Adipokine
  • Diabetes
  • Lipid metabolism
  • Obesity
  • Triglyceride secretion

ASJC Scopus subject areas

  • Physiology
  • Genetics

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