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(Circulation. 2008;117:2369-2376.)
© 2008 American Heart Association, Inc.

Vascular Medicine

Both Intestinal and Hepatic Lipoprotein Production Are Stimulated by an Acute Elevation of Plasma Free Fatty Acids in Humans

Hélène Duez, PhD; Benoît Lamarche, PhD; René Valéro, MD, PhD; Mirjana Pavlic, MD; Spencer Proctor, PhD; Changting Xiao, PhD; Linda Szeto, MSc; Bruce W. Patterson, PhD; Gary F. Lewis, MD

From the Departments of Medicine and Physiology, Division of Endocrinology and Metabolism, University of Toronto, Toronto, Canada (H.D., R.V., M.P., C.X., L.S., G.F.L.); Institut des Nutraceutiques et aliments fonctionnels, Université Laval, Québec, Canada (B.L.); Alberta Institute for Human Nutrition, University of Alberta, Edmonton, Alberta, Canada (S.P.); and Department of Internal Medicine, Washington University School of Medicine, St Louis, Mo (B.W.P.).

Correspondence to Dr Gary F. Lewis, Toronto General Hospital, 200 Elizabeth St, EN12-218, Toronto, Ontario, M5G 2C4, Canada. E-mail gary.lewis{at}uhn.on.ca

Received September 14, 2007; accepted February 15, 2008.

Background— Hepatic lipoprotein production has been shown previously to be regulated by free fatty acid (FFA) flux to the liver, whereas intestinal lipoprotein production is stimulated mainly by ingested fat absorbed from the intestinal lumen. Emerging evidence indicates that intestinal lipoprotein production is increased in insulin resistance and type 2 diabetes mellitus, conditions that are associated with increased levels of circulating FFAs. Here we investigated whether short-term elevation of plasma FFAs stimulates intestinal apolipoprotein (apo) B-48– and hepatic apoB-100–containing triglyceride-rich lipoprotein (TRL) production in humans in the fed state.

Methods and Results— TRL apoB-48 and apoB-100 metabolism were examined in 12 healthy men during a constant fed state. The studies were as follows, respectively: (1) Intralipid/heparin was infused intravenously immediately before and during the kinetics study to induce an 3-fold difference in plasma FFA compared with the saline study; (2) saline was infused intravenously as a control. ApoB-48– and apoB-100–containing TRL production and clearance were determined with a 12-hour primed constant infusion of [D3]L-leucine and multicompartmental kinetic modeling. TRL apoB-48 production rate was 69% higher in the Intralipid/heparin study than in the saline control (5.95±1.13 versus 3.53±0.58 mg/kg per day; P=0.027), and there was no significant difference in TRL apoB-48 clearance. TRL apoB-100 concentrations were also increased (P<0.001) and TRL apoB-100 production rate was 35% higher in the Intralipid/heparin study compared with saline (28±4 versus 21±3 mg/kg per day; P=0.020).

Conclusions— This is the first study to demonstrate that intestinal TRL apoB-48 production is increased after short-term elevation of plasma FFAs in humans in the fed state, similar to the well-described stimulation of hepatic TRL apoB100–containing particles by FFAs.

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Circulation 2008 117: 2309-2310. [Full Text]