Partial deficiency of CTRP12 alters hepatic lipid metabolism.
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.
Department of Physiology and Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Stefanie Y
SY
Tan
Department of Physiology and Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Hannah C
HC
Little
Department of Physiology and Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Xia
X
Lei
Department of Physiology and Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Shuoyang
S
Li
Department of Physiology and Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Susana
S
Rodriguez
Department of Physiology and Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland gwwong@jhmi.edu.
G William
GW
Wong
D054392:Adipokines / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D059305:Diet, High-Fat / Q000379:methods; D005260:Female; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D054392:Adipokines; D001786:Blood Glucose; C568466:C1qtnf12 protein, mouse; D007328:Insulin; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D005947:Glucose
adipokine; diabetes; lipid metabolism; obesity; triglyceride secretion