Effect of orlistat on postprandial lipemia, NMR lipoprotein subclass profiles and particle size.
Evidence suggests that metabolic phenomena during postprandial lipemia may be important in the pathogenesis of atherosclerosis. Both lipid concentrations and lipoprotein subclass patterns may be important cardiovascular risk modifiers. The pancreatic lipase inhibitor orlistat reduces fat absorption by 30% and is used for the treatment of overweight and obesity. We evaluated the effect of orlistat on postprandial lipemia and lipoprotein particle distribution after moderate-and high-fat meals in healthy volunteers. In this double-blind, randomized, cross-over study, 10 healthy young men received orlistat 120 mg plus a high-fat meal (HFO), orlistat plus a moderate-fat meal (MFO) or placebo plus a high-fat meal (HFP). Plasma triacylglycerol, glucose, insulin, and free fatty acids were measured at baseline (fasting) and postprandially for 8h. Lipoprotein subclass profile was assessed by nuclear magnetic resonance spectroscopy. The 8h postprandial mean triacylglycerol area under the curve (AUC) was significantly lower with MFO and HFO (0.79 versus 1.33 mmol/lh) versus HFP (4.33 mmol/lh; p=0.02). Mean change in large VLDL subclass concentration during the 4-8h and mean VLDL size after 8h was significantly lower with HFO and MFO versus HFP (p<0.001). Small HDL particle concentration decreased significantly with HFP versus MFO or HFO (p<0.001). There was no significant difference in postprandial concentrations of glucose, insulin or free fatty acids on the different regimens. The lowering of postprandial triacylglycerol AUC, shorter postprandial lipemia, lower concentration of large triacylglycerol-rich particles and decrease of VLDL particle size supports the hypothesis of a less atherogenic postprandial lipoprotein profile following orlistat ingestion.
Suter
Paolo M
PM
Department of Internal Medicine, Medical Policlinic, University Hospital, Rämistrasse 100, 8091 Zürich, Switzerland. paolo.suter@usz.ch
Marmier
Gabrielle
G
Veya-Linder
Caroline
C
Hänseler
Edgar
E
Lentz
Judith
J
Vetter
Wilhelm
W
Otvos
James
J
D000328:Adult; D019440:Anti-Obesity Agents / Q000008:administration & dosage*; D004041:Dietary Fats / Q000008:administration & dosage; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000188:drug therapy*; D007783:Lactones / Q000008:administration & dosage*; D008049:Lipase / Q000037:antagonists & inhibitors; D008074:Lipoproteins / Q000097:blood* / Q000737:chemistry; D008297:Male; D019906:Nuclear Magnetic Resonance, Biomolecular; D009765:Obesity / Q000097:blood / Q000188:drug therapy; D000077403:Orlistat; D010316:Particle Size; D019518:Postprandial Period / Q000187:drug effects
D019440:Anti-Obesity Agents; D004041:Dietary Fats; D007783:Lactones; D008074:Lipoproteins; D000077403:Orlistat; D008049:Lipase