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Submitted on November 18, 2003
Accepted on July 14, 2004
Departments 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.
It is not known whether intestinal lipoprotein production is stimulated by an acute elevation of plasma free fatty acids (FFA). We examined the effect of an intralipid and heparin infusion on intestinal lipoprotein production rate (PR) in insulin sensitive (CHOW fed), insulin resistant (60% fructose[FRUC] or 60% fat[FAT] fed), and insulin sensitized (FRUC or FAT plus rosiglitazone[RSG] treated) Syrian Golden Hamsters. Following 5 wks treatment, overnight fasted hamsters underwent in vivo Triton WR-1339 studies for measurement of apoB48 PR in large (Sf>400) and small (Sf100-400) lipoprotein fractions, with an antecedent 90-min infusion of intralipid 20% and heparin(IH) to raise plasma FFA levels 
5 to 8-fold vs. saline control study. IH markedly increased apoB48 PR in CHOW by 3 to 5 fold, confirmed ex vivo in pulse-chase experiments in primary cultured hamster enterocytes. Oleate but not glycerol infusion was associated with a similar elevation of apo B48 PR as intralipid and heparin. In FRUC and FAT, basal (saline control) apoB48 PR was 4-fold greater than CHOW and there was no further stimulation with IH in vivo and only minimal further stimulation ex vivo. RSG partially normalized basal apoB48 PR in FAT and FRUC and PR was markedly stimulated with IH. We conclude that intestinal lipoprotein production is markedly stimulated by an acute elevation of plasma FFAs in insulin sensitive hamsters, in which basal production is low, but minimally in insulin resistant hamsters, in which basal production is already elevated. With RSG treatment, basal PR is partially normalized and they become more susceptible to the acute FFA-stimulatory effect.
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