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Loss of CTRP1 disrupts glucose and lipid homeostasis.
Authors Rodriguez S, Lei X, Petersen PS, Tan SY, Little HC, Wong GW
Submitted By Submitted Externally on 7/30/2018
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2016
Date Published 10/1/2016
Volume : Pages 311 : E678 - E697
PubMed Reference 27555298
Abstract C1q/TNF-related protein 1 (CTRP1) is a conserved plasma protein of the C1q
family with notable metabolic and cardiovascular functions. We have previously
shown that CTRP1 infusion lowers blood glucose and that transgenic mice with
elevated circulating CTRP1 are protected from diet-induced obesity and insulin
resistance. Here, we used a genetic loss-of-function mouse model to address the
requirement of CTRP1 for metabolic homeostasis. Despite similar body weight,
food intake, and energy expenditure, Ctrp1 knockout (KO) mice fed a low-fat diet
developed insulin resistance and hepatic steatosis. Impaired glucose metabolism
in Ctrp1 KO mice was associated with increased hepatic gluconeogenic gene
expression and decreased skeletal muscle glucose transporter glucose transporter
4 levels and AMP-activated protein kinase activation. Loss of CTRP1 enhanced the
clearance of orally administered lipids but did not affect intestinal lipid
absorption, hepatic VLDL-triglyceride export, or lipoprotein lipase activity. In
contrast to triglycerides, hepatic cholesterol levels were reduced in Ctrp1 KO
mice, paralleling the reduced expression of cholesterol synthesis genes.
Contrary to expectations, when challenged with a high-fat diet to induce
obesity, Ctrp1 KO mice had increased physical activity and reduced body weight,
adiposity, and expression of lipid synthesis and fibrotic genes in adipose
tissue; these phenotypes were linked to elevated FGF-21 levels. Due in part to
increased hepatic AMP-activated protein kinase activation and reduced expression
of lipid synthesis genes, Ctrp1 KO mice fed a high-fat diet also had reduced
liver and serum triglyceride and cholesterol levels. Taken together, these
results provide genetic evidence to establish the significance of CTRP1 to
systemic energy metabolism in different metabolic and dietary contexts.


C1qtnf1C1q and tumor necrosis factor related protein 1


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