Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of orlistat, a nonabsorbed inhibitor of gastric and pancreatic lipases, was examined in patients with primary hyperlipidaemia (serum cholesterol > or = 6.2 mmol.l-1 and triglycerides < or = 5.0 mmol.l-1) not responsive to dietary change alone. In a multicentre, randomised, double-blind study, 103 men and 70 women received 30, 90, 180, or 360 mg or orlistat or placebo for 8 weeks. Total and low-density lipoprotein cholesterol levels were reduced by 4% and 5% with 30 mg orlistat, by 7% and 8% with 90 mg orlistat, by 7% and 7% with 180 mg orlistat and by 11% and 10% with 360 mg orlistat compared to placebo. High density lipoprotein cholesterol levels significantly decreased in the 360 mg orlistat group. Triglyceride levels significantly increased in the placebo group but not in the drug groups. Body weight decreased by 1.2 kg with 360 mg orlistat, despite a weight maintenance diet. Decreases in vitamin E and D levels occurred, although both vitamins remained within the normal range. Adverse effects from the gastrointestinal tract were frequent, but led to discontinuation of therapy in only seven patients. Orlistat is a new therapeutic drug for the treatment of hyperlipidaemia that may be particularly useful among overweight patients. Its potential place in therapy will await long-term studies. Vitamin supplementation should be considered during treatment.
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PMID:The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia. 795 33

Orlistat, a gastrointestinal lipase inhibitor, decreases fat absorption and thus it reduces caloric intake. The objectives of this placebo-controlled, double-blind, multicentre trial were to evaluate the efficacy of orlistat in terms of weight reduction, the effects on serum lipid levels and its tolerability profile. 119 obese patients (body mass index, BMI > or = 30 kg/m2) with hyperlipidemia (LDL-cholesterol > or = 4, 2 mmol/l) were randomized to receive either orlistat capsules 120 mg (n = 60) or placebo capsules (n = 59), three times daily, during 24 weeks. All patients were also on a mild hypocaloric diet. Mean weight reduction was 10.75 kg (10.7%) in orlistat group and 7.34 kg (7.5%) in placebo group. All serum lipid parameters improved in the orlistat group. The only adverse event more frequently noted with orlistat was stool fat. Orlistat in combination with diet provides increased weight loss than diet alone, improvements of serum lipids in subjects with hyperlipidemia and it has a good tolerability profile without systemic effects.
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PMID:Orlistat, a gastrointestinal lipase inhibitor, in therapy of obesity with concomitant hyperlipidemia. 1062 80

Orlistat (Xenical, Hoffmann-La Roche) is a powerful inhibitor of gastrointestinal lipase and as such, reduces fat absorption. Unlike other weight-reducing drugs it is minimally absorbed and has no effects in the CNS. Orlistat is indicated for patients with a body mass index (BMI) of at least 30 kg/m2 or 28 kg/m2 in the presence of obesity-associated complications, such as hypertension, diabetes mellitus, hyperlipidaemia and obstructive sleep apnoea. In clinical trials, orlistat (120 mg t.i.d.) in combination with life-style modification and a hypocaloric diet (30% of energy from fat) induced significantly more weight loss and improved health complications of obesity (diabetes, hypertension, hyperlipidaemia) compared to patients treated with diet alone. Side effects related to fat malabsorption, occurred in more than 20% of subjects during the first year of treatment and included oily faecal spotting, abdominal pain, flatus with discharge and fatty/oily stool. Side effects from orlistat diminished in the second year of treatment. Plasma concentrations of fat soluble vitamins decreased in orlistat-treated patients but did not usually fall below the normal range. No studies have evaluated the efficacy of orlistat or side effect profile beyond two years.
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PMID:Orlistat in the treatment of obesity. 2694 9

The socio-economic impact of obesity, one of the most prevalent medical disorders in Western society, is mainly due to its association with a higher risk of coronary heart disease. It is likely that atherosclerosis develops against a background of obesity as a result of the insulin resistance that is invariably present in overweight and obese subjects. Fasting plasma lipids may be normal in obese subjects, but they are usually affected by postprandial hyperlipidemia, which is probably due to competition between chylomicrons and VLDL for the same metabolic pathways. The basis for the impaired clearance of atherogenic chylomicron remnants is the fact that obesity causes hepatic apo B-VLDL overproduction, and thus leads to competition with chylomicrons and their remnants at the lipolytic pathway (lipoprotein lipase and hepatic lipase) and receptor level (LDL-receptor and remnant-receptor). The overproduction of VLDL is probably caused by an enhanced hepatic flux of free fatty acids in both the postprandial (from the lipolysis of triglyceride rich particles) and postabsorptive states (from adipocytes). Weight reduction by means of life-style changes, supported by medical interventions with inhibitors of intestinal fat absorption (e.g. Orlistat) or appetite suppressants (e.g. Sibutramine), is essential in order to decrease the risk of atherosclerosis. Furthermore, improvement of risk factors can be achieved by means of fibrate treatment to modulate fasting and postprandial triglyceride levels. Treatment with cholesterol synthesis inhibitors ("statins") may reduce hepatic VLDL production and increase the clearance of atherogenic remnants by upregulating LDL-receptors, thus leading to improved fasting lipid levels and enhanced clearance of chylomicron remnants. Finally, the use of thiazolidinedione derivatives to improve insulin sensitivity may be one of the options for reducing the risk of atherosclerosis in obese subjects.
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PMID:Obesity and free fatty acids: double trouble. 1143 90

Nonalcoholic steatohepatitis (NASH) may cause progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Treatment, thus far, has been restricted to diet and weight loss, but without compelling results. In this study we aimed to evaluate the efficacy of orlistat therapy in obese patients with NASH. Fourteen obese patients with NASH underwent liver biopsy prior to and subsequent to 6 months treatment with orlistat (120 mg tid). Hepatic fat extension was graded as normal, mild, moderate, or severe. Hepatic fibrosis was scored on a scale from 0 to 4, with 0 denoting no fibrosis and 4, cirrhosis. Portal inflammation was scored as 0-3, with 0 = normal, 1 = mild, 2 = moderate, and 3 = severe inflammation. Fourteen patients had NASH associated with diabetes, hyperlipidemia, or obesity. Orlistat reduced fatty infiltration in 10 patients (70%; P<0.01), 3 of whom had normal liver fat content after treatment. Orlistat improved inflammatory activity by 2 grades in 28% and by 1 grade in 50% of patients and effected no change in 22% of patients. Five patients (35%) returned to normal inflammatory activity. Orlistat improved hepatic fibrosis by 2 grades in three patients (21%) and by 1 grade in seven patients (50%). There was no change in four patients (28%). Orlistat lowered aminotransferases levels, total cholesterol, triglycerides and low-density lipoprotein, respectively. Insulin resistance index and malonyl dialdehyde levels improved significantly after orlistat therapy, whereas HbAic remained unchanged. In conclusion, in obese patients with NASH, liver fibrosis and inflammation improved after therapy with orlistat.
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PMID:Orlistat reverse fatty infiltration and improves hepatic fibrosis in obese patients with nonalcoholic steatohepatitis (NASH). 1740 56

Postprandial lipemia has emerged as an independent risk factor for coronary artery disease. In this systematic review we examined the effect of the medications used for the management of diabetes, obesity and dyslipidemia on postprandial lipemia. It should be mentioned that no standardization exists for a test meal and for the duration of observation postprandially to allow for direct comparisons between the published studies. Type 2 diabetes mellitus and insulin resistance are associated with enhanced postprandial lipemia. Insulin is effective in reducing both fasting and post prandial total triglyceride levels as well as triglycerides contained in the triglyceride-rich lipoprotein sub-fractions. Additionally, the newer rapid-acting insulin analogues seem to be more effective in the reduction of postprandial lipemia than the short-acting human insulins. Acarbose ameliorates postprandial lipemia and reduces the atherogenic chylomicron and very low density lipoprotein remnants. Metformin reduces both fasting and postprandial triglyceridemia, fasting and post-prandial free fatty acids and may increase the concentrations of the high density lipoprotein cholesterol. Sulfonylureas reduce fasting and postprandial triglyceride levels while data on the effect on high density lipoprotein levels are inconsistent. The effect of meglitinides on postprandial lipid metabolism is neutral. Rosiglitazone decreases fasting and postprandial free fatty acids but has no significant effect on fasting and postprandial triglycerides. Pioglitazone has additional beneficial effects on lipid metabolism because it reduces postprandial free fatty acids, fasting and postprandial triglycerides and increases high density lipoprotein cholesterol levels. Limited available data suggest that glucagon-like peptide-1 analogues and vildagliptin reduce postprandial lipemia through reduction of intestinally-derived triglycerides. No data exist on the effect of sitagliptin on postprandial lipemia. Orlistat improves postprandial lipemia by reducing the absorption of the dietary fat; no data exist on the effect of sibutramine and rimonabant on the metabolism of lipids in the postprandial state.
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PMID:The effects of medications used for the management of diabetes and obesity on postprandial lipid metabolism. 1899 2

Emerging evidences indicate that elevated cholesterol and triglyceride levels precede Alzheimer's disease (AD) pathology. High caloric intake based on saturated fat raises hyperlipidaemia and also promotes AD pathology. As a result, strategy that limits the absorption of dietary fat and attenuates hyperlipidemia could be a useful medication for protective treatment of AD. As an active site-directed inhibitor of digestive lipases, orlistat effectively reduces dietary fat absorption and decreases total cholesterol and triglyceride levels in plasma. Orlistat also potently inhibits lipoprotein lipase, monoacylglycerol lipase and diacylglycerol lipase, which are also involved in AD causation. Taken together, orlistat inhibits lipases activities, thereby reduces dietary fat intake and ameliorates hyperlipidemia, which indicates a therapeutic potential of orlistat in protecting against AD pathology.
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PMID:Therapeutic potential of lipase inhibitor orlistat in Alzheimer's disease. 1950 70

The present study was conducted to develop new inhibitors of pancreatic lipase and alpha-glucosidase from Chinese dietary herbs. Sixty-three dietary herbs from 39 taxonomic families were selected and extracted with aqueous ethanol or water. The extracts were then tested with in vitro enzyme assays for their ability to inhibit pancreatic lipase and alpha-glucosidase activities. Orlistat and acarbose were used as two positive controls. The extracts of Nelumbo nucifera, Curcuma longa, Piper longum and Morus alba showed strong pancreatic lipase inhibitory effects with IC50 at (28.00 +/- 5.51), (5.24 +/- 0.51), (14.76 +/- 2.58), (4.78 +/- 0.58), (3.41 +/- 0.67) mg x L(-1), respectively. These extracts also showed potent alpha-glucosidase inhibitory activities with IC50 at (1.98 +/- 0.13), (0. 18 + 0.007), (0.71 +/- 0.08), (0.077 +/- 0.005), (0.089 +/- 0.006) g x L(-1), respectively. The results provide useful information for developing new drugs or natural health products for hyperlipidemia and hypoglycemia from Chinese dietary herbs.
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PMID:[Screening of pancreatic lipase and alpha-glucosidase inhibitors from Chinese dietary herbs]. 2280 84