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- Title
Regulation of Intestinal Lipoprotein Production by Plasma Free Fatty Acids in Humans.
- Authors
Duez, Hélène M.; Lamarche, Benoît; Valéro, René; Pavlic, Mirjana; Xiao, Changting; Szeto, Linda; Patterson, Bruce W.; Proctor, Spencer; Lewis, Gary F.
- Abstract
Intestinal lipoprotein overproduction is a newly described feature of insulin resistance but the mechanism of this increase is not currently known. Increased plasma FFA flux in insulin resistance contributes to the overproduction of hepatic VLDL whereas intestinal lipoprotein production is stimulated mainly by ingested (luminal) fat. We have recently shown in the Syrian Golden hamster that intestinal lipoprotein production is also stimulated by an acute elevation of plasma FFAs. Here, we investigate whether an acute elevation of plasma FFAs stimulates intestinal apoB-48-containing triglyceride-rich lipoprotein (TRL) production rate (PR) in 6 healthy men. Each subject was studied on 3 occasions, in random order, 4 to 6 weeks apart. Study 1. Infusion of intralipid/heparin (IH) to acutely raise plasme FFAs approximately 2-fold, 2. Saline control study, 3. Glycerol control study. ApoB-48-containing TRL metabolism was examined in the steady state fed condition in all three studies with a 15-hour primed constant infusion of [D3]-L-leucine and multicompartmental modeling. TRL-apoB-48 levels were higher in the subjects receiving 1H compared to controls (p=0.036). This increase was associated with a 42% higher apoB-48 PR in the IH study compared to saline and glycerol control studies (mean±SEM 1.08±0.25 mg/kg.day in IH vs 0.76±0.21 in saline and 0.73±0.17 in glycerol study, p=ns due to high interindividual variability). There was no difference in clearance of apoB-48 TRL between the three studies. These are the first human data to demonstrate that intestinal apoB-48-containing TRL concentration and production rate tend to increase after acute elevation of plasma FFA in humans suggesting that increased FFAs may participate in intestinal lipoprotein particle overproductiom in insulin resistance states. Ongoing study of additional subjects will determine whether this increase is significant.
- Subjects
LIPOPROTEINS; INSULIN resistance; FATTY acids; TRIGLYCERIDES; HEPARIN; GLYCERIN
- Publication
Diabetes, 2007, Vol 56, pA238
- ISSN
0012-1797
- Publication type
Article