orlistat and Hyperlipidemias

To investigate, through a meta-analysis of clinical trials, the effect of two weight-reducing drugs, such as orlistat and sibutramine, on serum lipid profiles in overweight and obese subjects, independently of weight loss.. A systematic search strategy, incorporating the terms orlistat, sibutramine, fat, cholesterol, lipid profile, cardiovascular risk, was developed to identify randomized trials in MEDLINE from inception to the end of May 2005. Trial selection was limited by language of publication (English) and duration (6-12 months).. Fifteen and ten randomized, double-blind, placebo-controlled trials on orlistat and sibutramine respectively, were eligible for inclusion. In the 15 trials with orlistat, mean weight loss showed a significant correlation with mean reduction of total cholesterol (r=0.48; p<0.05), which maintained statistical significance after adjustment for mean weight loss (B=-2.81+/-1.28; p<0.05). Conversely, in the ten trials with sibutramine, treatment was not associated with a significant decrease in cholesterol levels after adjustment for weight loss (B=3.25+/-4.13; p not significant).. Orlistat or sibutramine, when individually compared to placebo, are effective in promoting significant weight loss. In addition, orlistat determines a significant reduction of total cholesterol, independent of weight loss itself. These observations indicate that orlistat is a useful adjunctive tool for improving cardiovascular risk factor profiles in overweight and obese patients.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Cardiovascular Diseases; Cyclobutanes; Humans; Hyperlipidemias; Hypolipidemic Agents; Lactones; Lipids; Middle Aged; Obesity; Orlistat; Treatment Outcome; Weight Loss

The obesity pandemic will likely have a significant impact on the global incidence of cardiovascular disease. Although the mechanisms linking obesity and cardiovascular disease are unclear, recent studies have implicated the adipocyte as a potentially important mediator of vascular complications. The adipocyte is no longer considered a passive storage depot for triglycerides and fatty acids, but rather an active metabolic organ capable of producing several factors, commonly referred to as adipokines, that may have effects on many physiological and pathophysiological processes. With increasing fat mass, several adipose-related factors are upregulated that may affect local and distant inflammatory processes, including atherothrombosis. Other factors, such as adiponectin, are downregulated with increasing fat mass. Although most adipokines are thought to promote vascular disease, several studies over the past few years indicate adiponectin is actually protective against both diabetes and vascular disease. There are now available pharmacologic agents capable of altering the adipocyte transcription profile. This review will focus on the potential impact of adipocyte-derived factors towards vascular disease and emerging therapeutic strategies that may alter these effects.

Topics: Adiponectin; Anti-Obesity Agents; Cardiovascular Diseases; Cyclobutanes; Diabetes Mellitus, Type 2; Humans; Hyperlipidemias; Hypertension; Lactones; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Risk Factors

The aim of this paper is to assess the clinical effectiveness of orlistat used for the management of obesity. Nineteen electronic databases were searched for randomized controlled trials evaluating the effectiveness of orlistat for weight loss or maintenance of weight loss in overweight or obese patients. Each included trial was assessed for methodological quality. Statistical pooling was performed when trials were considered to be sufficiently similar. Twenty-three trials were eligible for inclusion. Placebo-controlled trials recruiting patients with uncomplicated obesity reported statistically significant differences in favour of orlistat for weight loss and changes in obesity-related risk factors at all time points. Trials in obese patients with defined risk factors at baseline showed similar results, however, smaller effect sizes were observed in patients with type 2 diabetes. The effectiveness of orlistat relative to other anti-obesity drugs is currently unclear. When orlistat was added to simvastatin, this proved to be more effective for weight loss than either drug used individually. Orlistat use is associated with a higher incidence of gastrointestinal adverse events compared with placebo. In conclusion, orlistat is more effective than placebo in promoting weight loss, maintenance of weight loss, and improving cardiovascular risk factor profiles. Baseline parameters of patients seen in clinical practice should be taken into account when considering treatment.

Topics: Anti-Obesity Agents; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Humans; Hyperlipidemias; Lactones; Obesity; Orlistat; Placebos; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Weight Loss

Dyslipidaemia is more frequent in solid organ transplant recipients than in the general population, primarily as a result of immunosuppressive drug treatment. Both cyclosporin and corticosteroids are associated with dyslipidaemic adverse effects. In order to reduce the overall cardiovascular risk in these patients, lipid-lowering drugs have become widely used, especially HMG-CoA reductase inhibitors (statins). Cyclosporin, as well as most statins (lovastatin, simvastatin, atorvastatin and pravastatin) are metabolised by cytochrome P450 (CYP)3A4, so a bilateral pharmacokinetic interaction between these drugs is theoretically possible. However, results from several studies show that statins do not induce increased systemic exposure of cyclosporin. A small (but not clinically relevant) reduction in systemic exposure of cyclosporin has actually been shown in many studies. Cyclosporin-treated patients on the other hand show several-fold higher systemic exposure of all statins, both those that are metabolised by CYP3A4 and fluvastatin (metabolised by CYP2C9). Therefore, the mechanism for this interaction does not seem to be solely caused by inhibition of CYP3A4 metabolism, but it is probably also a result of inhibition of statin-transport in the liver, at least in part. Other lipid-lowering drugs, such as fibric acid derivatives, bile acid sequestrants, probucol, fish oils and orlistat are also used in solid organ transplant recipients. Most of them do not interact with cyclosporin, but there are reports indicating that both probucol and orlistat may reduce cyclosporin bioavailablility to a clinically relevant degree. There is no information on possible interaction effects of cyclosporin on the pharmacokinetics of lipid-lowering drugs other than statins, but it is not likely that any clinical relevant interference exists with fish oil, orlistat, probucol or bile acid sequestrants.

Topics: Acids, Acyclic; Area Under Curve; Bile Acids and Salts; Clinical Trials as Topic; Cyclosporine; Drug Interactions; Fish Oils; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Immunosuppressive Agents; Lactones; Organ Transplantation; Orlistat; Probucol; Quaternary Ammonium Compounds

Although comprehensive obesity treatment programmes were shown to induce weight loss and to improve risk factors and comorbidities, the weight reduction is moderate and most patients will rapidly regain weight. For these reasons, drugs have been developed or are in development to support and maintain weight loss. At present, two drugs are available for the adjunct treatment of obesity. Sibutramine is a centrally acting inhibitor of noradrenaline and serotonine reuptake, thereby decreasing caloric intake and increasing energy expenditure. Orlistat is a specific lipase inhibitor that impairs fat absorption, thereby reducing fat uptake. Both drugs have been found to be effective and safe in a number of clinical studies for up to two years. The current experience with these drugs raises questions related to the long-term efficacy with particular reference to cardiovascular end-points. In addition, other current and future pharmacological principles for weight reduction are discussed. There is no doubt that an evidence-based rational pharmacological treatment of obesity is still in an early stage.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Diabetes Mellitus, Type 2; Humans; Hyperlipidemias; Hypertension; Lactones; Obesity; Orlistat; Risk Factors; Treatment Outcome

Insulin resistance, and the compensatory hyperinsulinemia that results, has been linked to a host of defects including glucose intolerance, diabetes, hypertension, dyslipidemia, endothelial dysfunction, impaired fibrinolysis, and subclinical inflammation. Patients with this metabolic syndrome have a markedly increased risk for the development of atherothrombotic cardiovascular disease. The characteristic dyslipidemia of insulin resistance consists of elevated triglyceride and triglyceride-rich lipoprotein levels, low levels of high-density lipoprotein cholesterol, and increased concentrations of small, dense low-density lipoprotein cholesterol. Management of this dyslipidemia typically involves a dual approach. Lifestyle modification is an essential component of any successful treatment plan, but alone is usually insufficient to correct these lipoprotein abnormalities. Medications that diminish insulin resistance and directly alter lipoproteins are also necessary in the majority of cases. Combinations of therapeutic agents are often required to optimize attainment of treatment goals.

Topics: Cardiovascular Diseases; Enzyme Inhibitors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Lactones; Life Style; Lipase; Metformin; Niacin; Orlistat; Risk Factors

More than half of the men and women in the United States are overweight or obese. Obesity is associated with an increased risk for various diseases, most notably, hypertension, diabetes mellitus, dyslipidemia, and coronary heart disease (CHD). The location of excessive body fat, particularly in the visceral area, has the strongest association with these factors that comprise the insulin resistance syndrome. A reduction in as little as 10% of baseline weight has been shown to improve the control of blood pressure and glucose, as well as to reduce triglycerides and increase high-density lipoprotein (HDL) cholesterol. Therefore, obesity should be considered a predisposing CHD risk factor, and treatment with diet, exercise, and newer pharmacologic agents can help patients achieve and maintain desired weight-loss goals.

Topics: Anti-Obesity Agents; Arteriosclerosis; Coronary Disease; Diabetes Complications; Female; Humans; Hyperlipidemias; Hypertension; Insulin Resistance; Lactones; Male; Obesity; Orlistat; Risk Factors; Weight Loss

Orlistat (tetrahydrolipstatin) is an inhibitor of pancreatic and other lipases. As a pancreatic lipase inhibitor, it acts in the gastrointestinal lumen and is indicated for use in obesity. Serum total cholesterol and low density lipoprotein-cholesterol levels were reduced in obese, but otherwise healthy, patients during < or = 2 years' orlistat treatment; serum triglyceride and high density and very low density lipoprotein-cholesterol levels were unchanged in trials of < or = 12 weeks. Obese patients who were maintained on a hypocaloric diet and who received orlistat 360 mg/day for 12 weeks lost a significantly greater percentage of bodyweight than placebo recipients (5 vs 3.5%). In 2-year studies, weight loss was significantly greater in orlistat than in placebo recipients by the end of year 1; weight was further reduced or maintained in the second year, when a eucaloric diet was allowed, in orlistat but not placebo recipients. A greater proportion of orlistat than placebo recipients lost > 5% or > 10% of their initial bodyweight in 1- and 2-year studies.

Topics: Drug Tolerance; Humans; Hyperlipidemias; Lactones; Obesity; Orlistat

High-density lipoprotein (HDL) includes discrete subfractions. HDL exhibits anti-atherogenic properties, which have been partly linked to the activity of HDL-associated enzymes, such as the lipoprotein associated phospholipase A(2) (HDL-LpPLA(2)) and paraoxonase-1 (PON1).. We assessed in an open-label randomised study the effect of orlistat and ezetimibe, alone or in combination, on plasma HDL subclasses and HDL-associated enzyme activities in overweight and obese subjects (body mass index > 28 kg/m(2)) with hypercholesterolemia [total cholesterol > 200 mg/100 ml (5.2 mmol/l)].. Eighty-six people were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg, three times daily (O group), ezetimibe 10 mg/day (E group) or both (OE group) for 6 months. HDL subfractions were determined using a polyacrylamide gel-tube electrophoresis method.. Levels of HDL cholesterol (HDL-C) and apolipoprotein AI did not change significantly in any group. In group O the cholesterol concentration of HDL-2 subclass increased significantly, while the cholesterol of HDL-3 subclass decreased significantly. In groups E and OE HDL-2 subclass did not significantly change, while the cholesterol concentration of HDL-3 subclass decreased significantly. We observed a non-significant decrease in the HDL-LpPLA(2) and PON1 activity in all groups. However, the ratios of both enzyme activities to low-density lipoprotein cholesterol (LDL-C) levels (an index of atherogenicity) significantly increased in all groups.. Although HDL-C levels did not change after treatment with orlistat and ezetimibe, alone or in combination, there were alterations of the HDL-2 and HDL-3 subclasses. The activity of HDL-LpPLA(2) and PON1 per mg LDL-C increased significantly in all groups.

Topics: Adult; Anti-Obesity Agents; Anticholesteremic Agents; Aryldialkylphosphatase; Azetidines; Body Mass Index; Cholesterol, HDL; Diet, Fat-Restricted; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ezetimibe; Female; Humans; Hyperlipidemias; Lactones; Linear Models; Lipoproteins, HDL2; Lipoproteins, HDL3; Male; Middle Aged; Obesity; Orlistat; Phospholipases A2; Time Factors; Treatment Outcome

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.

Topics: Adult; Anti-Obesity Agents; Dietary Fats; Humans; Hyperlipidemias; Lactones; Lipase; Lipoproteins; Male; Nuclear Magnetic Resonance, Biomolecular; Obesity; Orlistat; Particle Size; Postprandial Period

The objective of this study was to quantify the effectiveness of orlistat plus a reduced calorie diet on decreasing cardiovascular disease risk in obese individuals with elevated low-density lipoprotein (LDL) cholesterol concentrations, and to compare the beneficial effects in patients with hypercholesterolemia only (type IIA) with those in subjects with combined dyslipidemia (type IIB). Hypercholesterolemic patients treated with orlistat lost more weight (mean +/- SEM 9.9 +/- 0.4 vs 6.1 +/- 0.5 kg, p = 0.0001) and had greater decreases in plasma cholesterol (p = 0.0001), LDL cholesterol (p = 0.0001), triglycerides (p = 0.06), glucose (p = 0.07), and insulin (p = 0.02) concentrations compared with the diet-only treated patients. The greater degree of weight loss in orlistat-treated subjects was similar irrespective of the form of dyslipidemia, and plasma total and LDL cholesterol and insulin levels decreased to a significantly greater degree (p <0.05) in those patients who received orlistat and who had either type IIA and IIB dyslipidemia. However, triglyceride and insulin concentrations decreased and high-density lipoprotein (HDL) cholesterol increased to a significantly greater degree following orlistat-assisted weight loss in patients with type IIB compared with type IIA subjects, which was associated with a significantly greater decrease in the ratio of LDL/HDL cholesterol. Thus, weight loss in response to a reduced calorie diet in obese hypercholesterolemic patients was associated with a significant decrease in plasma LDL cholesterol levels. The beneficial metabolic effects of weight loss were accentuated in response to orlistat administration, and the improvement was greatest in patients with combined dyslipidemia (type IIB).

Topics: Adult; Aged; Anti-Obesity Agents; Blood Glucose; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet, Reducing; Female; Humans; Hypercholesterolemia; Hyperlipidemias; Insulin; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat; Triglycerides; Weight Loss

Post-prandial lipaemia is prolonged and exaggerated in patients with Type 2 diabetes mellitus, with an accumulation of atherogenic triglyceride-rich lipoprotein remnants. We postulate that orlistat, a gastrointestinal lipase inhibitor, may cause changes in post-prandial lipoprotein metabolism by reducing dietary triglyceride absorption.. The acute effect of a single dose of 120 mg orlistat on post-prandial glucose, lipids, remnant lipoproteins and free fatty acids (FFA) was evaluated in a randomized, double-blind, placebo-controlled cross-over study of 63 overweight patients with Type 2 diabetes mellitus (body mass index 30.4 +/- 3.8 kg/m2). Either a single dose of orlistat or placebo was given before a standard mixed meal containing 70 g of fat and plasma triglyceride (TG), remnant-like particles cholesterol (RLP-C) and FFA were sampled at 2-h intervals for 8 h. RLP-C was measured by an immunoseparation assay and FFA by an enzymatic colorimetric method.. The concentrations of plasma TG (P < 0.0001), RLP-C (P = 0.003), and FFA (P < 0.0001) were significantly lower at 2 h after orlistat compared with placebo. Both plasma RLP-C (P = 0.04) and FFA (P < 0.0001) remained lower after orlistat than placebo at 4 h. The incremental area under the curve (iAUC) above baseline fasting level for both TG and RLP-C was significantly more reduced after orlistat than placebo (iAUC-TG 5.8 (3.7-8.2) mmol/l x h-1 vs. 5.7 (4.1-10.9), respectively, P = 0.04; iAUC-RLP-C: 0.53 (0.23-1.04) mmol/l x h-1 vs. 0.56 (0.35-1.40), respectively, P = 0.02). The test meal was well tolerated by all subjects, with only three subjects reporting faecal urgency after orlistat.. Orlistat has a beneficial effect on post-prandial lipaemia in overweight Type 2 diabetic patients and lowers plasma TG, RLP-C and FFA in the early post-prandial period.

Topics: Adult; Anti-Obesity Agents; Cholesterol; Cross-Over Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Fats; Double-Blind Method; Enzyme Inhibitors; Fatty Acids, Nonesterified; Female; Humans; Hyperlipidemias; Lactones; Lipase; Lipoproteins; Male; Middle Aged; Obesity; Orlistat; Postprandial Period; Triglycerides

To evaluate the efficiency of 6-month therapy with xenical (gastrointestinal lipase inhibitor) in combination with diet in patients with stable angina pectoris associated with obesity and hyperlipemia.. An open comparative randomized study of the efficiency of xenical in combination with diet was carried out in patients with stable angina pectoris concomitant with obesity and hyperlipemia. Thirty coronary patients aged 45-65 years with stable angina of effort (functional class I-II) with body weight index 28.1-45.6 kg/m2 (mean 33.5 kg/m2) were examined. All patients presented with dyslipemia (low density lipoprotein (LDL) cholesterol more than 4.14 mmol/liter, triglycerides (TG) more than 2.2 mmol/liter). Controls (n = 15) were treated with diets alone for 6 months. In the main group diets were supplemented by xenical in a dose of 360 mg/day.. Body weight index decreased in both groups (by 9.9% in the main group and by 4.2% in the control). Body weight stabilization during 6 months of treatment and the fact that it was slow and gradual were essential. In patients treated with xenical total cholesterol level decreased by 10.9% and of LDL cholesterol by 12.2% after 6 months (p < 0.05). Changes in the levels of high density lipoprotein cholesterol and TG were insignificant. The drug did not affect the incidence of angina attacks and improved exercise tolerance after 6-month therapy. Blood biochemistry (transaminases, alkaline phosphatase, glucose, and creatinine) changed negligibly. No side effects were observed; all patients received a complete 6-month course.. The results confirm that xenical (orlistat) can be used for long therapy of patients with stable angina of effort concomitant with obesity and hyperlipemia.

Topics: Aged; Angina Pectoris; Anti-Obesity Agents; Anticholesteremic Agents; Exercise Test; Female; Humans; Hyperlipidemias; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat

Orlistat (tetrahydrolipstatin) is an inhibitor of pancreatic and other lipases. As a pancreatic lipase inhibitor, it acts in the gastrointestinal lumen and is indicated for use in obesity. Serum total cholesterol and low density lipoprotein-cholesterol levels were reduced in obese, but otherwise healthy, patients during < or = 2 years' orlistat treatment; serum triglyceride and high density and very low density lipoprotein-cholesterol levels were unchanged in trials of < or = 12 weeks. Obese patients who were maintained on a hypocaloric diet and who received orlistat 360 mg/day for 12 weeks lost a significantly greater percentage of bodyweight than placebo recipients (5 vs 3.5%). In 2-year studies, weight loss was significantly greater in orlistat than in placebo recipients by the end of year 1; weight was further reduced or maintained in the second year, when a eucaloric diet was allowed, in orlistat but not placebo recipients. A greater proportion of orlistat than placebo recipients lost > 5% or > 10% of their initial bodyweight in 1- and 2-year studies.

Topics: Drug Tolerance; Humans; Hyperlipidemias; Lactones; Obesity; Orlistat

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.

Topics: Adult; Aged; Apolipoproteins; Body Weight; Cholesterol, VLDL; Diet, Fat-Restricted; Digestive System; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hyperlipidemias; Lactones; Lipase; Lipids; Lipoproteins; Male; Middle Aged; Orlistat; Triglycerides; Vitamins

The effect of tetrahydrolipstatin (THL), a recently developed pancreatic lipase inhibitor, on fasting plasma lipid levels and postprandial lipoprotein and retinyl palmitate (RP) metabolism was studied in 17 hyperlipidemic subjects, using an oral RP fat load (8 hours, 50 g fat/m2). During therapy with THL, fasting plasma cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein (apo) B concentrations decreased by 8% (P = .006), 9% (P = .002), and 10% (P = .002), respectively. The postprandial plasma triglyceridemia, which was expressed as the area under the 8-hour triglyceride (TG) curve, improved by 27% during THL therapy (P = .04) without changes in fasting plasma TG or high-density lipoprotein (HDL) cholesterol levels. The improved postprandial triglyceridemia was accompanied by a 19% reduction in circulating levels of chylomicrons and chylomicron remnants, determined by the decreased areas under the 8-hour RP curves. The most likely mechanisms involved are decreased formation of chylomicrons by a decrease of intestinal TG absorption as a consequence of THL treatment, as well as reduced delivery of dietary lipid and fatty acids to the liver and subsequent upregulation of hepatic LDL receptors. In agreement with the latter mechanism, the decrease in postprandial lipemia expressed as delta area under the TG curve was significantly related to the decrease (delta) in LDL cholesterol level during THL treatment (r = .81, P = .0001). The present data indicated that pancreatic lipase inhibition improved postprandial lipoprotein metabolism, which in turn resulted in lower plasma total and LDL cholesterol concentrations.

Topics: Administration, Oral; Apolipoproteins B; Cholesterol, HDL; Cholesterol, LDL; Chylomicrons; Diterpenes; Dose-Response Relationship, Drug; Double-Blind Method; Eating; Female; Humans; Hyperlipidemias; Intestinal Absorption; Lactones; Linear Models; Lipase; Lipids; Lipoproteins, LDL; Male; Middle Aged; Orlistat; Pancreas; Retinyl Esters; Triglycerides; Vitamin A

Obesity is a widespread medical problem, for which many drugs have been developed, each with its own limitations. Orlistat, a lipase inhibitor, functions as a fat absorption blocker and is a widely used over-the-counter drug in China. Psyllium husk, in contrast, is a food source rich in dietary fibre and is beneficial for weight loss because it reduces appetite. Here, it was investigated how psyllium husk treatments affect mice with a high-fat diet (HFD)-induced obesity, using obesity-related indices, metabolism indices, and gut microbiota, compared to orlistat treatments. Orlistat had a greater effect on weight loss, whereas psyllium husk had a greater effect at reducing serum and liver cholesterol and triglyceride levels. Treatments had similar effects on controlling the body fat rate, the expression level of farnesoid X receptor, sterol 27-hydroxylase and oxysterol 7-hydroxylase (CYP7B1) in the liver, and the regulation of major bile acids such as cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid in faecal content. However, the expression of CYP7A1 in the liver and the structures of faecal bile acids were different between the two drugs. Furthermore, although they also had similar effects on the gut microbiota at the phylum level, there were differences at the genus level for

Topics: Animals; Anti-Obesity Agents; Bile Acids and Salts; Diet, High-Fat; Hypercholesterolemia; Hyperlipidemias; Liver; Mice; Mice, Obese; Non-alcoholic Fatty Liver Disease; Obesity; Orlistat; Psyllium; Triglycerides; Weight Loss

Topics: Animals; Cyclic GMP; Diet, High-Fat; Hyperlipidemias; Inflammation; Male; Nitric Oxide; Nitric Oxide Synthase Type III; Nucleotides, Cyclic; Obesity; Orlistat; Propolis; Rats; Rats, Sprague-Dawley; Signal Transduction; Vasodilation

Leptin resistance and co-existing insulin resistance is considered as hallmark of diet-induced obesity. Here, we investigated therapeutic potential of hesperidin to improve leptin and insulin resistance using high fat diet (HFD)-induced obese experimental animal model. We also performed in silico studies to validate therapeutic effectiveness of hesperidin by performing protein-ligand docking and molecular dynamics simulation studies. Group 1 was identified as control group receiving vehicle only. Group 2 was marked as non-treated group receiving 60% HFD. While, other groups were treated daily with orlistat (120 mg/kg/d), hesperidin (55 mg/kg/d), combination of hesperidin (55 mg/kg/d) + orlistat (120 mg/kg/d). Hesperidin alone (P<0.001) and particularly in combination with orlistat (P<0.001), resulted in controlling the levels of HFD-altered biomarkers including random and fasting state of glycemia, leptin and insulin resistance. Similarly, hesperidin also improved the serum and tissue levels of leptin, interleukin-6 and tumor necrosis factor-alpha more significantly (P<0.05) when compared with that of orlistat. These results were found to be in accordance with the results of histopathological examination of pancreas, liver and adipose tissues. In-silico studies also proved that hesperidin binds to leptin receptor with higher affinity as compared to that of orlistat and induces the favorable variations in geometrical conformation of leptin receptor to promote its association with leptin which may lead to the cascades of reactions culminating the lipolysis of fats that may ultimately lead to cure obesity. The results of this study may be a significant expectation among the forthcoming treatment strategies for leptin and insulin resistance.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Obesity Agents; Diet, High-Fat; Disease Models, Animal; Drug Therapy, Combination; Hesperidin; Hyperlipidemias; Inflammation; Insulin Resistance; Leptin; Molecular Docking Simulation; Molecular Dynamics Simulation; Obesity; Orlistat; Rats, Wistar

The role of proinflammatory cytokines in adiposity is well established. The anti-inflammatory and antihyperglycemia effects of Boswellia serrata (B. Serrata) gum have been demonstrated by many investigators. The present study aimed to investigate the anti-obesity potential of B. serrata extract.. The effects of B. serrata extract on lipase activity and acute food intake were investigated. The present study aimed to investigate the anti-obesity potential of B. serrata extract. The effects on lipase activity and acute food intake were investigated. Body weight changes, biochemical and histopathological markers were demonstrated in rats fed a high-fat diet.. Boswellia serrata extract inhibited alterations in pancreatic lipase activity, but orlistat was more efficacious. B. serrata and ephidrene, but not orlistat, significantly suppressed cumulative food intake in mice. In obese rats, B. serrata or orlistat significantly decreased weight gain and weight of visceral white adipose tissue. B. serrata-treated animals exhibited a significant reduction in serum glucose, TC, TG, LDL-C, FFA, IL-1β, TNF-α, insulin and leptin levels of obese rat groups while HDL-C and adiponectin levels were significantly increased by orlistat or B. serrata extract. Histopathological examination of the liver revealed that B. serrata was more effective than orlistat in alleviating steatosis and adipocyte hypertrophy shown in obese control rats.. Boswellia serrata is as effective as orlistat in preventing obesity, hyperlipidemia, steatosis and insulin resistance. These actions may be mediated by suppression of food intake and decrease levels of TNF-α, IL-1β and leptin resistance along with increasing adiponectin.

Topics: Adipokines; Adiponectin; Adipose Tissue; Adiposity; Animals; Anti-Obesity Agents; Biomarkers; Body Weight; Boswellia; Cytokines; Diet, High-Fat; Eating; Hyperlipidemias; Insulin Resistance; Lipase; Male; Mice; Obesity; Orlistat; Plant Extracts; Polyphenols; Rats; Rats, Wistar; Resins, Plant

To determine the efficacy of Corchorus olitorius (C. olitorius) leaf extract in the prevention of metabolic syndrome induced in rats by high-fat diet (HFD) and compare it with that of orlistat.. Phytochemical analysis was performed. Effect of orlistat and C. olitorius extract on lipase activity and acute food intake were investigated. Body weight, biochemical parameters and histopathological examination were demonstrated.. Corchorus olitorius extract inhibited the pancreatic lipase activity, but orlistat was more potent. Cumulative food intake has not changed by the tested agents. In obese rats, C. olitorius or orlistat significantly decreased weight gain and visceral white adipose tissue. They exhibited a significant reduction in serum glucose, total cholesterol, triglycerides, low density lipoprotein cholesterol, free fatty acids, IL-1β, tumour necrosis factor-α (TNF-α), insulin and leptin levels of obese rat groups while high density lipoprotein cholesterol and adiponectin levels were significantly increased by them. Histopathological examination of the liver revealed that C. olitorius was more effective than orlistat in the alleviating of steatosis and adipocyte hypertrophy shown in obese control rats.. Corchorus olitorius is effective as orlistat in preventing obesity, hyperlipidaemia, steatosis and insulin resistance. These actions may be mediated by inhibiting of lipase activity, TNF-α, IL-1β and leptin resistance along with increasing of adiponectin.

Topics: Adiponectin; Animals; Anti-Obesity Agents; Corchorus; Cytokines; Diet, High-Fat; Hyperlipidemias; Insulin; Insulin Resistance; Leptin; Lipase; Male; Metabolic Syndrome; Obesity; Orlistat; Plant Extracts; Plant Leaves; Rats; Rats, Sprague-Dawley; Weight Gain

A high-fat diet (HFD) results in hyperlipidemia and an increase in oxidative stress. The purpose of this study was to investigate the preventive effect of embelin against hyperlipidemia and oxidative stress in HFD-induced obesity in rats. Male Wistar rats aged 12 weeks (150-200 g) were fed with an HFD for a period of 28 days to induce experimental obesity. HFD-induced obese rats were treated with embelin (50 mg/kg) or orlistat (10 mg/kg) for 21 days. A range of parameters were tested including body weight gain, body mass index (BMI), blood pressure, visceral fat pad weights, serum levels of glucose, insulin, leptin, apolipoprotein B (ApoB), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hepatic thiobarbituric acid-reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Twenty-one days of embelin (50 mg/kg) treatment produced effects similar to orlistat in reducing body weight gain, blood pressure, visceral fat pad weight, serum lipid levels, as well as coronary artery risk and atherogenic indices of HFD-fed rats. Embelin treatment also lowered the serum levels of glucose by 24.77 %, insulin by 35.03 %, and leptin by 43.39 %. Furthermore, embelin treatment significantly (p < 0.01) decreased the hepatic TBARS levels, while increasing the SOD, CAT, and GSH levels in obese rats. The present study indicated the preventive effect of embelin in HFD-induced obesity and its related complications. Embelin could be valuable in the development of new drug therapies to prevent obesity, hyperlipidemia, and oxidative stress.

Topics: Animals; Anti-Obesity Agents; Antioxidants; Benzoquinones; Diet, High-Fat; Embelia; Fruit; Humans; Hyperlipidemias; Lactones; Lipase; Lipid Metabolism; Male; Obesity; Orlistat; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Rats, Wistar

Orlistat is an inhibitor of lipase which splits triglycerides into free fatty acides and glycerol. This drug, by inhibiting hydrolysis of triglycerides, is the cause of significant loss of fat in the faeces. 13 obese and 15 nonobese subjects were examined. Obese subjects received orlistat (Xenical, F. Hoffmann La Roche Ltd, Switzerland) 3 x 120 mg/d. Treatment with orlistat for 16 weeks was followed by a significant fall of BMI and MAP, insulinemia, insulin/glucose ratio, leptinemia, serum total cholesterol, triglycerides, HDL-cholesterol and 25-OH-D concentration respectively. Orlistat did not influence significantly serum LDL-cholesterol concentration but unexpectedly increased plasma levels of folic acid, vitamin B12 and NPY.. (1) Monitoring of plasma 25-OH-D levels in obese patients on orlistat therapy seems to be mandatory. (2) In spite of significant changes (in opposite direction) in leptinemia and serum NPY level observed in obese subjects treated with orlistat, presence of a functional relationship between these hormones could not be confirmed.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Carbohydrates; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Enzyme Inhibitors; Female; Hormones; Humans; Hypercholesterolemia; Hyperlipidemias; Insulin; Lactones; Leptin; Lipase; Lipids; Male; Neuropeptide Y; Obesity; Orlistat; Poland; Time Factors; Treatment Outcome; Triglycerides; Vitamins; Weight Loss