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Increased Hepatic CD36 Expression Contributes to Dyslipidemia Associated with Diet-Induced Obesity

¹Cardiovascular Research Group and the Departments of Pediatrics Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
²CIHR Group on the Molecular and Cell Biology of Lipids, Departments of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
³Department of Cell Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
⁴Baylor College of Medicine, USDA/ARS Children's Nutrition Research Center, Houston, Texas, USA
⁵Faculty of Pharmacy and Department of Pharmacology, Faculty of Medicine, Université de Montreal, Montreal, Quebec, Canada

Objective: The etiology of type 2 diabetes (T2D) often involves diet-induced obesity (DIO), which is associated with elevated plasma fatty acids (FA) and lipoprotein associated triglycerides (TG). Since aberrant hepatic FA uptake may contribute to this, we investigated whether increased expression of a FA transport protein (CD36) in the liver during DIO contributes to the dyslipidemia that precedes development of T2D.

Research design and methods: We determined the effect DIO has on hepatic CD36 protein expression as well as the functional consequence of this in terms of hepatic TG storage and secretion. In addition, in vivo adenoviral gene delivery of CD36 to the livers of lean mice was performed to determine if increased hepatic CD36 protein was sufficient to alter hepatic FA uptake, TG storage and secretion.

Results: CD36 protein levels in the liver are significantly elevated during DIO, which is correlated with increased hepatic TG storage and secretion. These alterations in liver lipid storage and secretion were also observed upon forced expression of hepatic CD36 in the absence of DIO and were accompanied with a marked rise in hepatic FA uptake in vivo, demonstrating that increased CD36 expression is sufficient to recapitulate the aberrant liver lipid handling observed in DIO.

Conclusions: Increased expression of hepatic CD36 protein in response to DIO is sufficient to exacerbate hepatic TG storage and secretion. As these CD36-mediated effects contribute to the dyslipidemia that often precedes the development of T2D, increased hepatic CD36 expression likely plays a causative role in the pathogenesis of T2D.

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