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

  1. Debby P.Y. Koonen1,
  2. René L. Jacobs2,
  3. Maria Febbraio3,
  4. Martin E. Young4,
  5. Carrie-Lynn M. Soltys1,
  6. Huy Ong5,
  7. Dennis E. Vance2 and
  8. Jason R.B. Dyck1
  1. 1Cardiovascular Research Group, Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
  2. 2CIHR Group on the Molecular and Cellular Biology of Lipids, Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
  3. 3Department of Cell Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
  4. 4Baylor College of Medicine, USDA/ARS Children’s Nutrition Research Center, Houston, Texas
  5. 5Faculty of Pharmacy and Department of Pharmacology, Faculty of Medicine, Université de Montreal, Montreal, Quebec, Canada
  1. Address correspondence and reprint requests to Dr. Jason R.B. Dyck, 474 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2. E-mail: jason.dyck{at}


OBJECTIVE—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.

RESEARCH DESIGN AND METHODS—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.

RESULTS—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.

CONCLUSIONS—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.


  • Published ahead of print at on 29 August 2007. DOI: 10.2337/db07-0907.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted August 23, 2007.
    • Received July 3, 2007.
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  1. Diabetes vol. 56 no. 12 2863-2871
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