orlistat and Hypertriglyceridemia

This review considers drug combinations and newer treatment strategies for patients with severe hypertriglyceridemia. Hypertriglyceridemia is associated with an atherogenic metabolic profile and in most studies with increased cardiovascular disease risk. Patients with severe hypertriglyceridemia also have increased incidence of pancreatitis. All types of severe hypertriglyceridemia are associated with a reduction in lipoprotein lipase activity. Patients with severe hypertriglyceridemia and abdominal pain or pancreatitis should be hospitalized and treated with hypolipidemic drugs and, if needed, with insulin/dextrose infusion or therapeutic apheresis. Fibrates are the first-line treatment in patients with severe hypertriglyceridemia. Omega-3 fatty acids and niacin are very useful drugs for patients with hypertriglyceridemia. Statins in high doses exhibit a significant hypotriglyceridemic activity. Drugs that interfere with chylomicron production such as orlistat are also useful for hypertriglyceridemic patients. In most patients with severe hypertriglyceridemia drug combinations are needed to maintain an acceptable triglyceride concentration. Gene therapy is under development for patients with known genetic abnormalities of triglyceride metabolism. Clinicians should be vigilant for the recognition and prompt treatment of patients with severe hypertriglyceridemia aimed to avoid the serious complication of pancreatitis and to reduce their cardiovascular risk.

Topics: Algorithms; Blood Component Removal; Cardiovascular Diseases; Diet, Fat-Restricted; Fatty Acids, Omega-3; Fibric Acids; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Lactones; Life Style; Niacin; Orlistat; Practice Guidelines as Topic; Severity of Illness Index; Triglycerides

The present study investigated inhibition of pancreatic lipase and metabolic effects of high caloric diet in rats. The Passiflora nitida hydroethanol leaf extract (PNE) was used in in vitro assays or administered to rats to study dyslipidemia. Inhibition of lipase in vitro was studied by a spectrophotometric assay using orlistat as the positive control. The effects of PNE on reduction of postprandial triglyceride were studied by oral fat-overloading in rats. Metabolic alterations were induced using the cafeteria diet and 4 weeks post-treatment with PNE or orlistat and blood samples were collected and biochemical analyses were performed. Liver and retroperitoneal fat tissues were obtained to analyze weight and steatosis. IC50 (lg/mL) values for pancreatic lipase inhibition were 21.2 ± 0.8 and 0.1 ± 0.01 for PNE and orlistat, respectively. Oral administration of lipid emulsion resulted in postprandial hypertriglyceridemia at 3 h postadministration and when rats were then administered PNE and orlistat there was decreased of triglyceride levels by 15 % compared to control. Although the energy consumption by the cafeteria diet had been higher, there was no significant weight gain observed in the study groups. The cafeteria diet resulted in a significant increase of weight in the retroperitoneal fat and hypertriglyceridemia levels that could be significantly reduced by PNE and orlistat treatment. We hypothesized that PNE administration prevented the hypertriglyceridemia in rats with a high caloric diet, possibly owing to reduction of lipid absorption and pancreatic lipase inhibition.

Topics: Adipose Tissue; Animals; Body Weight; Diet; Energy Intake; Enzyme Inhibitors; Hypertriglyceridemia; Lactones; Lipase; Lipids; Liver; Male; Orlistat; Passiflora; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Triglycerides

Dyslipidemia is frequently found in association with obesity. Obesity-related dyslipidemia is characterized by elevated triglycerides, elevated VLDL, increased apo-B, decreased HDL cholesterol and increased small dense LDL particles. This combination of lipid abnormalities is particularly atherogenic and, along with related comorbidities, explains the increased cardiovascular risk seen in obesity. Weight loss, through diet, medication and/or surgery all result in beneficial effects upon serum lipids. Dietary modification and lifestyle change are essential components in the management of obesity-related dyslipidemia. Many patients, however, require pharmacotherapy to achieve lipid goals.

Topics: Anti-Obesity Agents; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia; Hypolipidemic Agents; Lactones; Life Style; Niacin; Obesity; Orlistat; Weight Loss

Topics: Adult; Anti-Obesity Agents; Anticholesteremic Agents; Atorvastatin; Dietary Fiber; Drug Therapy, Combination; Fatty Acids, Omega-3; Female; Heptanoic Acids; Humans; Hypertriglyceridemia; Lactones; Male; Middle Aged; Niacin; Orlistat; Pyrroles; Statistics, Nonparametric; Treatment Outcome

Hypertriglyceridemic very low density lipoproteins (HTG-VLDL, S(f) 60-400) are not taken up by HepG2 cells. However, addition of bovine milk lipoprotein lipase (LPL) at physiological concentrations markedly stimulates uptake. In the present study, we determined whether: a) LPL catalytic activity is required for uptake, b) LPL functions as a ligand, and c) cell surface hepatic triglyceride lipase (HL) and/or proteoglycans are involved. Incubation of HepG2 cells with HTG-VLDL plus LPL (8 ng/ml) increased cellular cholesteryl ester (CE) 3.5-fold and triglyceride (TG) 6-fold. Heat-inactivation of LPL abolished the effect. Addition of tetrahydrolipstatin (THL, an LPL active-site inhibitor) to HTG-VLDL + LPL, inhibited the cellular increase in both CE and TG by greater than 90%. Co-incubation of HTG-VLDL + LPL with heparin, heparinase, or heparitinase, blocked CE accumulation by 70%, 48%, and 95%, respectively, but had no effect on the increase in cellular TG. Pre-treatment of cells with 1 mM 4-methylumbelliferyl-beta-D-xyloside, (beta-xyloside) to reduce cell surface proteoglycans inhibited the increase in CE induced by HTG-VLDL + LPL by 78%. HTG-VLDL remnants, prepared in vitro and isolated free of LPL activity, stimulated HepG2 cell CE 2.8-fold in the absence of added LPL, a process inhibited with THL by 66%. Addition of LPL (8 ng/ml) to remnants did not further enhance CE accumulation. HepG2 cell HL activity, released by heparin, was inhibited 95% by THL. The amount of HL activity and immunoreactive mass, released by heparin, was reduced 50-60% in beta-xyloside-treated cells. These results indicate that physiological concentrations of LPL promote HepG2 cell uptake of HTG-VLDL primarily due to remnant formation and that LPL does not play a major role as a ligand. HL activity and cell surface proteoglycans significantly enhance the subsequent uptake of VLDL remnants.

Topics: Animals; Cattle; Cell Line; Cholesterol Esters; Enzyme Inhibitors; Glycosides; Heparin; Heparin Lyase; Hot Temperature; Humans; Hypertriglyceridemia; Lactones; Lipase; Lipoprotein Lipase; Lipoproteins, LDL; Lipoproteins, VLDL; Liver; Orlistat; Polysaccharide-Lyases; Proteoglycans