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This version published online on October 14, 2004
Endocrinology, doi:10.1210/en.2004-1143
A more recent version of this article appeared on January 1, 2005
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*Compound via MeSH
*Substance via MeSH

Submitted on August 27, 2004
Accepted on October 6, 2004

Intestinal lipoprotein overproduction, a newly recognized component of insulin resistance, is ameliorated by the insulin sensitizer rosiglitazone: studies in the fructose-fed Syrian Golden hamster

Gary F. Lewis*, Kristine Uffelman, Mark Naples, Linda Szeto, Mehran Haidari, and Khosrow Adeli

Department of Medicine and Physiology, Division of Endocrinology & Metabolism, and the Department of Laboratory Medicine & Pathobiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

* To whom correspondence should be addressed. E-mail: gary.lewis{at}uhn.on.ca.

Objective: We investigated whether intestinal lipoprotein overproduction in a fructose-fed, insulin resistant hamster model is prevented with insulin sensitization.

Methods: Syrian Golden hamsters were fed either chow (CHOW), 60% fructose for 5 weeks (FRUC), CHOW for 5 weeks with the insulin sensitizer rosiglitazone (RSG) added for the last 3 weeks (CHOW+RSG) or 60% fructose plus rosiglitazone (FRUC+RSG).

Results: In vivo triton studies showed a 2 to 3-fold increase in large (Sf >400) and smaller (Sf 100-400) triglyceride rich lipoprotein (TRL) particle apoB48 but not triglyceride secretion with fructose feeding in the fasted state (P < 0.01), and partial normalization with rosiglitazone in fructose fed hamsters. Ex vivo pulse-chase labeling of enterocytes confirmed the oversecretion of apoB48 lipoproteins with fructose feeding. Intestinal lipoprotein oversecretion was associated with increased expression of microsomal triglyceride transfer protein (MTP) expression. With rosiglitazone treatment of fructose fed hamsters, there was a ~50% reduction in apoB48 secretion from primary cultured enterocytes and amelioration of the elevated MTP mass and activity in fructose fed hamsters. In contrast, in the postprandial state the major differences between nutritional and drug intervention protocols were evident in TRL triglyceride and not apo B48 secretion rates.

Conclusions: The data suggest that intestinal lipoprotein overproduction can be prevented with the insulin sensitizer rosiglitazone.




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