title: Effects of intralipid-induced hypertriglyceridemia on plasma high-density lipoprotein metabolism in the cynomolgus monkey.
abstract: Low plasma levels of high-density lipoprotein (HDL) and apolipoprotein (apo) A-I often accompany human hypertriglyceridemia. In an animal model of hypertriglyceridemia, the lipoprotein lipase (LPL)-inhibited cynomolgus monkey, we reported that plasma levels of apo A-I were decreased and the fractional catabolic rate (FCR) of HDL apo was increased. To explore whether hypertriglyceridemia alone would alter plasma apo A-I levels and catabolism, hypertriglyceridemia was produced by intravenous (IV) infusion of 20% Intralipid into female cynomolgus monkeys. Baseline plasma triglyceride (TG) levels averaged 106 mg/dL. With infusion of 200 mg/kg/h Intralipid TG, plasma TG levels peaked at 967 mg/dL (range, 413 to 1,069; n = 6). More prolonged or more severe hypertriglyceridemia caused serious complications in several monkeys. Despite the severe hypertriglyceridemia, HDL TG content, HDL apoproteins, and plasma apo A-I levels did not markedly change, suggesting that very little HDL remodeling had occurred. Kinetic studies of HDL protein and apo A-I were performed in four pairs of monkeys. The two tracers were removed from the plasma at identical rates. In five pairs of animals, apo A-I turnover during control and Intralipid-induced hypertriglyceridemia was not significantly different. We hypothesize that apo A-I FCR is a function of HDL composition. Because Intralipid infusion did not alter HDL composition to the same degree as did LPL inhibition, its effects on HDL apo catabolism were not apparent.
authors.affiliation: Department of Medicine, Columbia University College of Physicians & Surgeons, New York, NY.
authors.forename: I J
authors.initials: IJ
authors.lastname: Goldberg
authors.forename: T M
authors.initials: TM
authors.lastname: Vanni
authors.forename: R
authors.initials: R
authors.lastname: Ramakrishnan
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005260:Female; D015228:Hypertriglyceridemia / Q000139:chemically induced* / Q000378:metabolism*; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008252:Macaca fascicularis; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D005217:Fat Emulsions, Intravenous; D008055:Lipids; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D008071:Lipoprotein Lipase