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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #243624
Title: Increased hepatic CD36 expression contributes to dyslipidemia associated with diet-induced obesity

Author
item KOONEN, DEBBY - University Of Alberta
item JACOBS, RENE - University Of Alberta
item FEBBRAIO, MARIA - Lerner Research Institute
item YOUNG, MARTIN - Children'S Nutrition Research Center (CNRC)
item SOLTYS, CARRIE-LYNN - University Of Alberta
item ONG, HUY - Universite De Montreal
item VANCE, DENNIS - University Of Alberta
item DYCK, JASON R - University Of Alberta

Submitted to: Diabetes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/23/2007
Publication Date: 12/1/2007
Citation: Koonen, D.P., Jacobs, R.L., Febbraio, M., Young, M.E., Soltys, C.M., Ong, H., Vance, D.E., Dyck, J. 2007. Increased hepatic CD36 expression contributes to dyslipidemia associated with diet-induced obesity. Diabetes. 56(12):2863-2871.

Interpretive Summary: An excess of fatty acids (beyond the ability to burn them as a fuel) has been associated with several diseases, including obesity and diabetes. CD36 is a protein in the body that is typically believed to allow fatty acids to be transported into the cell. The present study is the first to show that when CD36 levels are artificially increased in the liver of mice, this resulted in increased fatty acids and lipids in the blood, similar to that seen during obesity and diabetes in humans. The implications are that altered liver CD36 levels contribute to metabolic disease states, such as diabetes.

Technical Abstract: The etiology of type 2 diabetes often involves diet-induced obesity (DIO), which is associated with elevated plasma fatty acids and lipoprotein associated triglycerides. Since aberrant hepatic fatty acid uptake may contribute to this, we investigated whether increased expression of a fatty acid transport protein (CD36) in the liver during DIO contributes to the dyslipidemia that precedes development of type 2 diabetes. We determined the effect DIO has on hepatic CD36 protein expression and the functional consequence of this in terms of hepatic triglyceride 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 fatty acid uptake and triglyceride storage and secretion. During DIO, CD36 protein levels in the liver are significantly elevated, and these elevated levels correlate with increased hepatic triglyceride 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 fatty acid uptake in vivo, demonstrating that increased CD36 expression is sufficient to recapitulate the aberrant liver lipid handling observed in DIO. Increased expression of hepatic CD36 protein in response to DIO is sufficient to exacerbate hepatic triglyceride storage and secretion. As these CD36-mediated effects contribute to the dyslipidemia that often precedes the development of type 2 diabetes, increased hepatic CD36 expression likely plays a causative role in the pathogenesis of type 2 diabetes.