Prg4 KO Mice are Protected from High Fat Diet-induced Metabolic Disruptions

Abstract

36 Proteoglycan 4 (Prg4) is highly expressed in metabolic tissues. The proteoglycan is a target gene for the nuclear receptor peroxisome proliferator receptor gamma which acts as metabolic switch. So, our aim was to investigate the function of Prg4 in metabolism. Male Prg4 knock-out (KO) mice and wild-type (WT) littermates were challenged with a obesogenic high fat diet (45% kcal lard fat) for 16 weeks. To stimulate the development of a diabetic phenotype, 10% fructose water was provided. Mice were subjected to an oral glucose tolerance test to investigate glucose handling. Flux studies with glycerol [3H]oleate-labeled VLDL-like particles were performed to determine the uptake of triglyceride-derived fatty acids in metabolically active organs. No significant difference in body weight was observed between both groups. However, both plasma triglyceride levels (-16%; p hepatic steatosis in Prg4 KO mice is most likely driven by decreased de novo lipogenesis , as judged by the significantly reduced expression of lipogenic genes ACC and SCD1 (-21% and -38%; p fatty acids . White adipose tissue of Prg4 KO mice showed decreased uptake of triglyceride-derived fatty acids (-46%; p CD68 and MCP1 was lower in Prg4 KO adipose tissue as compared to that of WT controls (2.9- and 5.1-fold decrease; p oral glucose tolerance test (AUC: -29%; p Prg4 KO and WT mice have a similar obesogenic potential, however Prg4 KO mice are protected from high fat diet-induced metabolic disruptions.