HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: db07-0907v1 56/12/2863    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Koonen, D. P.Y. Articles by Dyck, J. R.B. Search for Related Content PubMed PubMed Citation Articles by Koonen, D. P.Y. Articles by Dyck, J. R.B. Social Bookmarking                What's this?

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

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

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}ualberta.ca

Abbreviations: ALT, alanine aminotransferase; BMIPP, 15-p-[¹²³I]iodophenyl-3-(R,S)-methyl pentadecanoic acid; DIO, diet-induced obesity; NEFA, nonesterified fatty acid; SPECT, single photon emission computed tomography; VLDL, very-low-density lipoprotein

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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. Holvoet, D.-H. Lee, M. Steffes, M. Gross, and D. R. Jacobs Jr Association Between Circulating Oxidized Low-Density Lipoprotein and Incidence of the Metabolic Syndrome JAMA, May 21, 2008; 299(19): 2287 - 2293. [Abstract] [Full Text] [PDF]