title: Intestinal scavenger receptor class B type I as a novel regulator of chylomicron production in healthy and diet-induced obese states.
abstract: The small intestine contributes to diabetic dyslipidemia through the overproduction of apolipoprotein B48 (apoB48)-containing chylomicron particles. An important regulator of chylomicron generation is dietary lipid absorption, underlining the potential involvement of intestinal lipid transporters for developing dyslipidemia. Intestinal expression of scavenger receptor class B type I (SR-BI) has been found to be upregulated in animal models of insulin resistance. Here we characterized the potential importance of SR-BI in contributing to chylomicron production and postprandial hypertriglyceridemia in vivo. Postprandial triglyceride (TG)-rich lipoprotein (TRL) production was characterized in hamsters treated with the SR-BI inhibitor to block lipid transport-1 (BLT-1) under healthy conditions or conditions of diet-induced obesity and dyslipidemia. BLT-1 (1 mg/kg) or vehicle was administered acutely in chow-fed hamsters or gavaged twice daily over 10 days during high-fructose, high-fat, high-cholesterol (FFC) feeding. Effects of acute SR-BI inhibition by BLT-1 were confirmed in healthy fat-loaded rats. Finally, plasma lipid levels were compared between SR-BI(-/-) mice and their wild-type counterparts fed either chow or a 12-wk high-fat diet. Acute BLT-1 treatment reduced postprandial plasma and TRL TG levels in healthy hamsters and rats. Chronic BLT-1 treatment of FFC-fed hamsters blunted diet-induced weight gain and fasting hypertriglyceridemia, and lowered postprandial TRL-TG, -cholesterol, and -apoB48 levels. Finally, SR-BI(-/-) mice displayed lower plasma and TRL TG levels relative to wild type, and diet-induced weight gain and postprandial hypertriglyceridemia were hindered in SR-BI(-/-) mice. We conclude that intestinal SR-BI is a critical regulator of postprandial lipoprotein production, emphasizing its potential as a target for preventing diabetic dyslipidemia.
authors.affiliation: Department of Molecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; and.
authors.forename: Marsel
authors.initials: M
authors.lastname: Lino
authors.affiliation: Department of Molecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; and.
authors.forename: Sarah
authors.initials: S
authors.lastname: Farr
authors.affiliation: Department of Molecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada;
authors.forename: Chris
authors.initials: C
authors.lastname: Baker
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Fuller
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Trigatti
authors.affiliation: Department of Molecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; and khosrow.adeli@sickkids.ca.
authors.forename: Khosrow
authors.initials: K
authors.lastname: Adeli
mesh_terms: D000818:Animals; D002914:Chylomicrons / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D059305:Diet, High-Fat / Q000009:adverse effects; D050171:Dyslipidemias / Q000209:etiology / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D002914:Chylomicrons; D051122:Scavenger Receptors, Class B; D014280:Triglycerides
keywords: apolipoprotein; insulin resistance