orlistat and Insulin-Resistance

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age. Obesity is frequently present in these patients and plays a key role in the pathogenesis of both the endocrine and metabolic abnormalities of the syndrome, particularly infertility, hyperandrogenism and insulin resistance (IR). Diet and exercise is the mainstay of management of obesity in patients with PCOS. In contrast, the eff ects of antiobesity agents on weight and on the obesityrelated characteristics of the syndrome remain unclear. The aim of the present review is to summarize the current data on the eff ects of antiobesity drugs approved in Europe (orlistat, liraglutide 3 mg od and naltrexone/bupropion) on weight loss in patients with PCOS and to discuss their impact on the endocrine, reproductive and metabolic abnormalities of this population. Several studies reported that orlistat induces weight loss, improves IR and reduces androgen levels in PCOS. In contrast, data regarding the eff ects of the dose of liraglutide that is approved for the treatment of obesity (3 mg od) are very limited. Liraglutide 1.2-1.8 mg od results in weight loss in these patients but does not aff ect IR or androgen levels. Finally, there are no studies that evaluated naltrexone/bupropion in patients with PCOS and early studies reported conflicting results regarding the eff ects of naltrexone monotherapy on weight, IR and androgen levels. In conclusion, orlistat appears to have a role in the management of overweight and obese patients with PCOS whereas more studies are needed to clarify the role of liraglutide and naltrexone/bupropion.

Topics: Androgens; Anti-Obesity Agents; Bupropion; Drug Combinations; Female; Humans; Insulin Resistance; Liraglutide; Naltrexone; Obesity; Orlistat; Polycystic Ovary Syndrome; Weight Loss

Weight loss, regular exercise, and diet composition modification seem to improve biochemical and histologic abnormalities. Other therapies directed at insulin resistance, oxidative stress, cytoprotection, and fibrosis may also offer benefits. Insulin sensitizers and vitamin E seem to be the most promising; however, they cause side effects. A multifaceted approach of lifestyle modifications, weight loss, and pharmacotherapy can be used in combination, but no single treatment approach has proved universally applicable to the general population with nonalcoholic steatohepatitis (NASH). Continuous clinical and preclinical studies on existing and potential drugs are needed to improve treatment of nonalcoholic fatty liver disease/NASH.

Topics: Angiotensin Receptor Antagonists; Anti-Inflammatory Agents, Non-Steroidal; Anti-Obesity Agents; Anticholesteremic Agents; Antioxidants; Cannabinoid Receptor Antagonists; Cholagogues and Choleretics; Fatty Acids, Omega-3; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Insulin Resistance; Lactones; Metformin; Non-alcoholic Fatty Liver Disease; Orlistat; Pentoxifylline; Piperidines; Probiotics; Pyrazoles; Rimonabant; Synbiotics; Thiazolidinediones; Ursodeoxycholic Acid; Vitamin E

Obesity is now a major international health concern. It is increasingly common in young women with reproductive, metabolic and psychological health impacts. Reproductive health impacts are often poorly appreciated and include polycystic ovary syndrome (PCOS), infertility and pregnancy complications. PCOS is the most common endocrine condition in women and is underpinned by hormonal disturbances including insulin resistance and hyperandrogenism. Obesity exacerbates hormonal and clinical features of PCOS and women with PCOS appear at higher risk of obesity, with multiple underlying mechanisms linking the conditions. Lifestyle intervention is first line in management of PCOS to both prevent weight gain and induce weight loss; however improved engagement and sustainability remain challenges with the need for more research. Medications like metformin, orlistat, GLP1 agonists and bariatric surgery have been used with the need for large scale randomised clinical trials to define their roles.

Topics: Adipokines; Bariatric Surgery; Combined Modality Therapy; Comorbidity; Diet, Reducing; Exercise Therapy; Female; Glucagon-Like Peptide 1; Gonadal Steroid Hormones; Humans; Hyperandrogenism; Inflammation; Insulin Resistance; Lactones; Life Style; Metformin; Models, Biological; Motivation; Obesity; Obesity, Abdominal; Orlistat; Polycystic Ovary Syndrome; Prevalence; Sympathetic Nervous System; Weight Loss

Triglycerides participate in key metabolic functions such as energy storage, thermal insulation and as deposit for essential and non-essential fatty acids that can be used as precursors for the synthesis of structural and functional phospholipids. The liver is a central organ in the regulation of triglyceride metabolism, and it participates in triglyceride synthesis, export, uptake and oxidation. The metabolic syndrome and associated diseases are among the main concerns of public health worldwide. One of the metabolic syndrome components is impaired triglyceride metabolism. Diseases associated with the metabolic syndrome promote the appearance of hepatic alterations e.g., non-alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the molecular actions involved in impaired triglyceride metabolism and its association with hepatic diseases. We discuss mechanisms that reconcile the chronic inflammation and insulin resistance, and new concepts on the role of intestinal micro-flora permeability and proliferation in fatty liver etiology. We also describe the participation of oxidative stress in the progression of events leading from steatosis to steatohepatitis and fibrosis. Finally, we provide information regarding the mechanisms that link fatty acid accumulation during steatosis with changes in growth factors and cytokines that lead to the development of neoplastic cells. One of the main medical concerns vis-a-vis hepatic diseases is the lack of symptoms at the onset of the illness and, as result, its late diagnosis. The understandings of the molecular mechanisms that underlie hepatic diseases could help design strategies towards establishing markers for their accurate and timely diagnosis.

Topics: Fatty Liver; Fibrosis; Humans; Insulin Resistance; Lactones; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Orlistat; Oxidative Stress; Triglycerides

The prevalence of obesity and the metabolic syndrome (MS) is on the rise, and subsequently the hepatic manifestation of MS, nonalcoholic fatty liver disease (NAFLD), has become a common entity in clinical practice. Most patients with NAFLD face medical complications related to their underlying MS in other organ systems; however, a small but significant group of patients with the more aggressive form of fatty liver, nonalcoholic steatohepatitis (NASH), are at risk of developing cirrhosis and hepatocellular carcinoma. As patients are generally asymptomatic, often their disease goes unrecognized. This is particularly true for NASH, where liver biopsy is currently required to make the diagnosis. Once diagnosed, no one treatment has been shown to be universally efficacious and those that are of benefit are not without side effects. Effective treatment regimens directed at both decreasing insulin resistance as well as the processes leading to necroinflammation and hepatic fibrosis have been investigated and include lifestyle modification, surgical therapies, and pharmacotherapy. This review focuses on current and potential future therapies for NASH.

Topics: Animals; Antioxidants; Bariatric Surgery; Body Mass Index; Cannabinoids; Cholagogues and Choleretics; Comorbidity; Fatty Liver; Glucagon-Like Peptide 1; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Insulin Resistance; Lactones; Life Style; Metformin; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Thiazolidinediones; Treatment Outcome; Ursodeoxycholic Acid; Weight Loss

Topics: Age Factors; Androgens; Dyslipidemias; Humans; Hypertension; Hypolipidemic Agents; Insulin Resistance; Kidney Failure, Chronic; Lactones; Metabolic Syndrome; Orlistat; Progesterone-Binding Globulin; Testosterone; Tumor Necrosis Factor-alpha; Tunica Intima

The present article reviews the diagnostic criteria for pediatric obesity and its comorbidities. Treatment is also reviewed, including promotion of physical activity, and dietetic, pharmacologic and surgical treatment.

Topics: Anti-Obesity Agents; Appetite Depressants; Cardiovascular Diseases; Child; Combined Modality Therapy; Cyclobutanes; Fatty Liver; Gastric Bypass; Humans; Hypercholesterolemia; Hypertension; Insulin Resistance; Lactones; Metabolic Syndrome; Obesity; Orlistat; Risk Factors

Obesity has reached global epidemic proportions because of an increasingly obesogenic environment. This review examines the association between obesity, and in particular visceral fat, as a risk factor for cardiovascular disease and mortality.. The World Health Organization defines obesity based on the body mass index. Recently the waist-to-hip ratio has been shown to be a significantly stronger predictor of cardiovascular events than body mass index. The metabolic syndrome and its evolving definition represent a cluster of metabolic risk factors which help predict cardiovascular disease and mortality. Although insulin resistance plays a central role in the pathophysiology of the metabolic syndrome, there is limited support for therapy with insulin sensitizers, thiazolidinediones, in patients with coronary artery disease. The current anti-obesity drugs, orlistat and sibutramine, have only a modest effect on weight loss. The blockade of the endocannabinoid system with rimonabant, however, may be a promising new strategy.. Obesity is associated with significant increase in cardiovascular risk. Lifestyle modification remains the cornerstone of management although anti-obesity medications may be indicated in high risk individuals with comorbid disease.

Topics: Appetite Depressants; Body Fat Distribution; Body Mass Index; Cardiovascular Diseases; Cyclobutanes; Humans; Inflammation; Insulin Resistance; Intra-Abdominal Fat; Lactones; Life Style; Lipid Metabolism; Metabolic Syndrome; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Thiazolidinediones; Waist-Hip Ratio

The need for an effective and safe medical treatment of nonalcoholic fatty liver disease is urgent due to its high prevalence and progressive character. At the moment, therapeutic strategies are largely empirical and based on the control of associated clinical conditions (especially obesity, type 2 diabetes mellitus, and hypertriglyceridemia) and the use of some specific drugs (insulin sensitizing agents, cytoprotectives, antioxidants, and anticytokines) as an attempt to counteract known elements of the pathogenesis. None of these specifics measures have been found to display enough evidence to recommend their clinical use. It is indispensable to join efforts in coordinated networks to define, as soon as possible, the best treatment and the best time to start it.

Topics: Anti-Obesity Agents; Anticholesteremic Agents; Atorvastatin; Chromans; Diabetes Mellitus, Type 2; Fatty Liver; Heptanoic Acids; Humans; Hypoglycemic Agents; Insulin Resistance; Lactones; Metabolic Syndrome; Metformin; Obesity; Orlistat; Prevalence; Pyrroles; Rosiglitazone; Thiazolidinediones; Troglitazone

The prevalence of Type 2 diabetes mellitus (DM-2) is increasing throughout the world and poses a major public health concern. With the majority of patients DM-2 are overweight or obese and weight loss is generally recommended, both as a first-line therapy and as an adjunct to pharmacological therapies. However, it is generally acknowledged that weight loss, a difficult goal for many overweight and obese individuals, is especially difficult for those with DM-2 and there is interest in whether pharmacological adjuncts may be useful for this purpose. Orlistat is an intestinal lipase inhibitor previously approved for the treatment of obesity. During the past several years, clinical trials have been completed concerning the use of orlistat in the treatment of overweight or obese patients with DM-2. The purpose of this review is to examine the results of these clinical trials. Data on > 2500 orlistat-treated patients with DM-2 are reviewed and summarised. Orlistat therapy led to greater weight loss and improved metabolic control in overweight and obese patients with DM-2.

Topics: Anti-Obesity Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Resistance; Lactones; Obesity; Orlistat; Sulfonylurea Compounds; Weight Loss

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

The relief of insulin resistance is one of the two therapeutic targets of the treatment of type 2 diabetes. Insulin-sensitizers are therefore complemental with other oral diabetic drugs. The treatment of insulin resistance was for a long time limited to dietary and exercise programmes, a biguanide, metformine, and benfluorex, a phenylethylamine derivative; the mechanisms of action of both drugs are now better understood and their indications more precisely targeted. A new therapeutic class, the thiazolidinediones (troglitazone, rosiglitazone, pioglitazone) has recently completed the family of insulin-sensitizing agents. These drugs, which should be soon available in France, act by a different way than metformin, which has been recently identified as the peroxisomes proliferator-activated receptor. The role of antilipolytic agents, which might increase glucose uptake by reducing free fatty acid production and oxidation is under evaluation, as well as the potential benefit of orlistat, an inhibitor of lipid digestion which has been proved effective, in addition to hypocaloric diet, in the management of obese patients.

Topics: Administration, Oral; Chromans; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Exercise; Fenfluramine; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Lactones; Lipase; Metformin; Orlistat; Peroxisome Proliferators; Pioglitazone; Rosiglitazone; Thiazoles; Thiazolidinediones; Troglitazone

Topics: Body Mass Index; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Metformin; Obesity; Orlistat; Overweight; Polycystic Ovary Syndrome

Patients with non-alcoholic fatty liver disease (NAFLD) exhibit features of metabolic syndrome, including a high body mass index, central obesity, high blood pressure, and abnormal lipid profile values. Orlistat, an intestinal lipase enzyme inhibitor, improves insulin resistance. We aimed to investigate the effects of short-term therapy with orlistat on the components of metabolic syndrome associated with NAFLD and explore its effect on liver fibrosis scores.. An open-label placebo-controlled clinical study using orlistat for 12 weeks was carried out on 50 patients with NAFLD. They were divided into a placebo group (Group I) and an orlistat treatment group (120 mg per day, Group II). The diagnosis of NAFLD was made by ultrasonography and laboratory investigations. Anthropometric and blood pressure measurements and hepatic liver enzymes, fasting lipids, and blood glucose levels were determined before and after treatment. Lipid indices including cholesterol (Chol-I), triglyceride (TG-I), triglyceride-glucose (TYG-I), and the scores for lipid fibrosis using the NAFLD fibrosis score (NFS) and Fibrosis-4 score (Fib-4) were also determined.. Orlistat significantly improved the anthropometric and metabolic indices (TG-I, TYG-I) and liver enzymes. Orlistat demonstrated a favorable impact on the NAS and Fib-4 scores for liver fibrosis.. Orlistat improves the components of metabolic syndrome, leading to the improvement of insulin resistance and thereby improves fatty infiltration of the liver. To a lesser extent, orlistat improved the liver fibrosis scores.

Topics: Humans; Insulin Resistance; Liver Cirrhosis; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Orlistat

To evaluate the effect of Diane-35, alone or in combination with orlistat or metformin, on androgen and body fat percentage parameters in Chinese overweight and obese polycystic ovary syndrome (PCOS) patients with insulin resistance.. A total of 240 PCOS women were randomly allocated to receive Diane-35 alone (D group), Diane-35 plus orlistat (DO group), Diane-35 plus metformin (DM group), or Diane-35 plus orlistat plus metformin (DOM group). Serum TT, DHEA-S, androstenedione, SHBG, FT, FAI, body fat, and body fat percentage were assessed at baseline and after 12 weeks of treatment.. Significant changes in serum TT, SHBG, and FAI were observed in all treatment groups compared with baseline. DHEA-S and androstenedione significantly decreased in the DO, DM, and DOM groups after treatment. FT only significantly decreased in the DOM group. Body fat and body fat percentage significantly decreased in the DO and DOM groups. Compared with the D group, DHEA-S significantly decreased in the DO, DM, and DOM groups (F = 4.081, p = 0.008); SHBG significantly increased in the DOM group (F = 3.019, p = 0.031); and FAI significantly decreased in the DO group (χ. Diane-35 in combination with orlistat or metformin is more effective in reducing androgen than Diane-35 alone. Orlistat is more effective in reducing body fat percentage than metformin. In addition, orlistat has mild side-effects and is better tolerated compared with metformin.

Topics: Adipose Tissue; Adult; Androgen Antagonists; Androgens; Cyproterone Acetate; Drug Combinations; Ethinyl Estradiol; Female; Humans; Insulin Resistance; Metformin; Obesity; Orlistat; Overweight; Polycystic Ovary Syndrome; Treatment Outcome

A range of studies showed confusing data about the relationship between obesity, weight reduction and circulating total insulin-like growth factor -1 (IGF-1). The aim of the study was to compare the influence of orlistat (IO), metformin (IM), or calorie-restricted diet (LC) on IGF-1, with special respect to insulin-resistance status. One hundred and fourteen obese women aged from 18 to 40 years were divided into insulin sensitive (IS) and insulin resistant (IR) groups and received a low calorie diet (LC), or an isocaloric diet and 500 mg metformin twice daily (IM), or isocaloric diet with 120 mg orlistat three times daily (IO). Before and after the intervention anthropometric parameters, serum lipid profile, serum concentrations of alanine aminotransferase, aspartate aminotransferase, insulin, glucose, IGF-1, HOMA-IR (homeostatic model assessment), and visceral adiposity index (VAI), and their changes were registered. Although the reductions in weight and body fat were comparable in IS and IR groups, only women with IR showed a significant increase in IGF-1 concentration as a result of all interventions. We found significant positive correlations of ΔIGF-1 with initial and Δ values of: HOMA-IR, triglyceride/high-density cholesterol ratio, VAI. IR premenopausal women show significant increase in IGF-1 serum concentrations regardless the method of intervention. The increase in IGF-1 was parallel to the improvement of insulin resistance parameters.

Topics: Adult; Anti-Obesity Agents; Caloric Restriction; Diet; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Insulin-Like Growth Factor I; Intra-Abdominal Fat; Metformin; Obesity; Orlistat; Premenopause

Evidence suggests that endocannabinoid system activation through the cannabinoid receptor 1 (CB1) is associated with enhanced liver injury, and CB1 antagonism may be beneficial. The aim of this study was to determine the impact of rimonabant (CB1 antagonist) on alanine aminotransferase (ALT), a hepatocellular injury marker, and a hepatic inflammatory cytokine profile.. Post hoc review of 2 studies involving 50 obese women with PCOS and well matched for weight, randomised to weight reducing therapy; rimonabant (20 mg od) or orlistat (120 mg tds), or to insulin sensitising therapy metformin, (500 mg tds), or pioglitazone (45 mg od). No subject had non-alcoholic fatty liver disease (NAFLD).. Treatment with rimonabant for 12 weeks reduced both ALT and weight (p < 0.01), and there was a negative correlation between Δ ALT and Δ HOMA-IR (p < 0.001), but not between Δ ALT and Δ weight. There was a significant reduction of weight with orlistat (p < 0.01); however, orlistat, metformin and pioglitazone had no effect on ALT. The free androgen index fell in all groups (p < 0.05). The inflammatory marker hs-CRP was reduced by pioglitazone (p < 0.001) alone and did not correlate with changes in ALT. The inflammatory cytokine profile for IL-1β, IL-6, IL-7, IL-10, IL12, TNF-α, MCP-1 and INF-γ did not differ between groups. None of the interventions had an effect on biological variability of ALT.. Rimonabant through CB1 receptor blockade decreased serum ALT that was independent of weight loss and hepatic inflammatory markers in obese women with PCOS without NAFLD.. ISRCTN58369615 (February 2007; retrospectively registered) ISRCTN75758249 (October 2007; retrospectively registered).

Topics: Alanine Transaminase; Anti-Obesity Agents; Body Mass Index; Cannabinoid Receptor Antagonists; Case-Control Studies; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin Resistance; Lactones; Liver Diseases; Metformin; Obesity; Orlistat; Pioglitazone; Piperidines; Polycystic Ovary Syndrome; Prognosis; Pyrazoles; Receptor, Cannabinoid, CB1; Retrospective Studies; Rimonabant; Thiazolidinediones; Weight Loss

Obesity is associated with numerous health problems, particularly metabolic and cardiovascular complications. This study aimed to assess the effects that, nine months of pharmacological intervention with orlistat or sibutramine, on obese Malaysians' body weight and compositions, metabolic profiles and inflammatory marker.. Seventy-six obese subjects were randomly placed into two groups. The first group received three daily 120 mg dosages of orlistat for nine months (n=39), and the second group received a once daily 10 or 15 mg dosage of sibutramine for nine months (n=37). Baseline measurements for weight, body mass index (BMI), waist circumference (WC), body fat percentage (BF), visceral fat (VF), adiponectin, fasting plasma glucose (FPG), fasting insulin, pancreatic B cell secretory capacity (HOMA%B), insulin sensitivity (HOMA%S), insulin resistance (HOMA-IR) and serum high sensitivity C-reactive protein (hs-CRP) were performed and repeated during the sixth and ninth months of treatment.. Twenty-four subjects completed the trial in both groups. For both groups, weight, BMI, WC, BF, VF, HOMA-IR and hs-CRP were significantly lower at the end of the nine month intervention. However, there were no significant differences between the two groups for these parameters with nine months treatment. There was a significant decrease in FPG in orlistat group; while fasting insulin and HOMA%B reduced in sibutramine group. For both groups, there were also significant increases in adiponectin levels and HOMA%S at the end of the nine month intervention.. Nine months of treatment with orlistat and sibutramine not only reduced weight but also significantly improved BMI, WC, BF, VF, FPG, adiponectin, fasting insulin, HOMA%B, HOMA%S, HOMA-IR and hs-CRP. These improvements could prove useful in the reduction of metabolic and cardiovascular risks in obese subjects.

Topics: Adiponectin; Adolescent; Adult; Aged; Asian People; Blood Glucose; Body Fat Distribution; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cyclobutanes; Fasting; Humans; Insulin; Insulin Resistance; Intra-Abdominal Fat; Lactones; Malaysia; Middle Aged; Obesity; Orlistat; Risk; Treatment Outcome; Waist Circumference; Young Adult

The present study investigates the combined effect of diet, physical exercise and Orlistat for 24 weeks, on serum anti-Müllerian hormone (AMH) levels in overweight and obese women with polycystic ovary syndrome (PCOS) and in overweight and obese controls. Sixty-one (61) selected women with PCOS and 20 overweight and obese controls followed an energy-restricted diet, physical exercise plus Orlistat administration (120 mg, 3 times per day) for 24 weeks. At baseline, week 12 and week 24, serum levels of AMH, FSH, LH, PRL, androgens, sex hormone-binding globulin (SHBG), glucose, and insulin were measured and Free Androgen Index (FAI) and Insulin Resistance (IR) indices were calculated. In PCOS women, serum AMH levels increased after 12 and 24 weeks of treatment. After 12 weeks LH and SHBG were increased, while Testosterone decreased. After 12 and 24 weeks, FAI was decreased and all indices of IR were significantly improved. We concluded that in overweight and obese women with PCOS Orlistat administration, combined with diet and physical exercise, for 24 weeks, resulted in significant weight loss, improvement of hyperandrogenism and insulin sensitivity, and increased serum AMH levels.

Topics: Adult; Anti-Mullerian Hormone; Anti-Obesity Agents; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Exercise; Female; Humans; Hyperandrogenism; Insulin Resistance; Lactones; Luteinizing Hormone; Obesity; Orlistat; Overweight; Polycystic Ovary Syndrome; Testosterone; Up-Regulation; Weight Loss; Young Adult

  The behavioural approach is usually slow and not always sufficient to achieve optimal targets in weight and metabolic control in obese diabetic patients, and a pharmacological treatment is often necessary. The aim of this study was to compare the effects of orlistat and placebo on body weight, glycaemic and lipid profile and insulin resistance in patients with type 2 diabetes.. Two hundred and fifty-four obese, diabetic patients were enrolled in this study and randomized to take orlistat 360mg or placebo for 1year. We evaluated at baseline and after 3, 6, 9 and 12months body weight, waist circumference (WC), body mass index (BMI), glycated haemoglobin (HbA(1c) ), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), lipid profile, retinol-binding protein-4 (RBP-4), resistin, visfatin and high-sensitivity C-reactive protein (Hs-CRP).. We observed a significant reduction in body weight, WC, BMI, lipid profile, RBP-4 and visfatin in the orlistat group but not in control group. Faster improvements in HbA(1c) , PPG, FPI, HOMA-IR, resistin and Hs-CRP were recorded with orlistat than with placebo. A similar decrease in FPG was seen in the two groups. Significant predictors of change in insulin resistance (HOMA-IR) were RBP-4 and resistin concentration in the orlistat group (r=-0·53, P<0·05, and r=-0·59, P<0·01, respectively).. To the best of our knowledge, this is the first study investigating the effect of orlistat on insulin resistance and markers of inflammation. Orlistat improved lipid profile and led to faster glycaemic control and insulin resistance parameters than the control, without any serious adverse event. Orlistat also improved RBP-4 and visfatin, effects not observed with placebo.

Topics: Anti-Obesity Agents; Biomarkers; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Follow-Up Studies; Humans; Inflammation; Insulin Resistance; Lactones; Lipids; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity; Orlistat; Retinol-Binding Proteins, Plasma

To evaluate the effects of 1-year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight, glycemic and lipid control, and inflammatory parameters in obese type 2 diabetic patients. Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) > 8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomized to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day. We evaluated the following parameters at baseline and after 3, 6, 9, and 12 months: body weight, body mass index (BMI), glycated hemoglobin (HbA(1c) ), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), adiponectin (ADN), leptin, tumor necrosis factor-α (TNF-α), vaspin, and high-sensitivity C-reactive protein (Hs-CRP). We observed a better decrease in body weight, glycemic profile, HOMA-IR, LDL-C, and ADN and a faster improvement in FPI, TC, Tg, leptin, TNF-α, Hs-CRP with orlistat plus L-carnitine compared to orlistat alone. We also recorded an improvement in vaspin with orlistat plus l-carnitine not reached with orlistat alone. Orlistat plus L-carnitine gave a better improvement in body weight, glycemic and lipid profile compared to orlistat alone; furthermore, a faster and better improvement in inflammatory parameters was observed with orlistat plus L-carnitine compared to orlistat alone.

Topics: Adiponectin; Anti-Inflammatory Agents; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Body Weight; C-Reactive Protein; Carnitine; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inflammation; Insulin; Insulin Resistance; Lactones; Leptin; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Obesity; Orlistat; Thiazolidinediones; Time Factors

Visceral adipose tissue-derived serpin (vaspin) has been regarded as a novel adipokine with potential insulin sensitizing properties. We investigated the changes of serum vaspin concentration in response to weight reduction, and the associations between changes in serum vaspin concentrations and changes of anthropometric and metabolic variables in obese subjects after weight reduction. We performed a longitudinal clinical intervention study on 63 obese persons enrolled in a 12-week weight reduction program that included lifestyle modification and adjuvant treatment with the antiobesity agent orlistat. Anthropometric variables, lipid profiles, fasting glucose, fasting insulin, and serum vaspin concentrations were measured. Statistical analyses were performed according to the homeostasis model assessment of insulin resistance (HOMA(IR)). Serum vaspin concentrations decreased significantly in responders (≥2% reduction in baseline weight), but not in nonresponders (<2% reduction in baseline weight). Changes in serum vaspin concentrations were significantly correlated with body weight, BMI, waist circumference, and hip circumference in the higher, but not in the lower, HOMA(IR) group. In multivariate linear regression analysis, change in serum vaspin concentrations in the higher, but not in the lower, HOMA(IR) group was positively correlated with change in BMI and negatively correlated with initial HOMA(IR) level. The associations between changes in serum vaspin concentrations and changes in anthropometric and metabolic parameters differed according to insulin resistance status in obese subjects. These relationships were more prominent in the higher HOMA(IR) group. Insulin resistance may influence the correlations between changes in serum vaspin concentration and related metabolic variables.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Body Weight; Female; Hip; Humans; Insulin Resistance; Lactones; Life Style; Longitudinal Studies; Male; Obesity; Orlistat; Serpins; Treatment Outcome; Waist Circumference; Weight Loss

To evaluate the effects of 1-year treatment with orlistat compared with placebo on different inflammatory parameters in type 2 obese diabetic patients.. Two hundred and fifty-four type 2 diabetic patients were randomized to take orlistat 120 mg three times a day or placebo for 12 months. We evaluated at baseline and after 3, 6, 9 and 12 months: leptin, tumor necrosis factor (TNF)-alpha, adiponectin (ADN), vaspin and high-sensitivity C-reactive protein (HS-CRP), body weight, waist circumference, body mass index (BMI), lipid profile, glycemic profile, fasting plasma insulin (FPI) and homeostasis model assessment insulin resistance index (HOMA-IR).. Regarding inflammatory parameters, there was a significant improvement of ADN and TNF-alpha, and a faster decrease of leptin and HS-CRP in the orlistat group compared with the control group. We also recorded a significant reduction of body weight and BMI with orlistat, but not with placebo. A faster improvement of glycemic profile and FPI was obtained with orlistat compared with the controls. Also, there was a significant reduction of lipid profile with orlistat, not reached with placebo.. Orlistat was more effective than placebo in ameliorating inflammatory parameters such as ADN and TNF-alpha, and anthropometric parameters.

Topics: Adiponectin; Anti-Obesity Agents; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; C-Reactive Protein; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Inflammation Mediators; Insulin; Insulin Resistance; Italy; Lactones; Leptin; Lipids; Male; Middle Aged; Obesity; Orlistat; Placebo Effect; Serpins; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Waist Circumference

Our study wants to evaluate the effects of one year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight, glycemic and lipid control, and insulin resistance state in type 2 diabetic patients. Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) > 8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA(1c), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, high sensitivity-C reactive protein (Hs-CRP). We observed a faster, and better decrease of body weight, HbA(1c), FPG, PPG, LDL-C, HOMA-IR with orlistat plus L-carnitine compared to orlistat. A faster improvement of TC, Tg, FPI, resistin, RBP-4, visfatin, and Hs-CRP was reached with orlistat plus L-carnitine compared to orlistat. We can safely conclude that the association of orlistat plus L-carnitine was better than orlistat in improving body weight, glycemic and lipid profile, insulin resistance, and inflammatory parameters and no significant adverse events were recorded.

Topics: Anti-Obesity Agents; Body Weight; Carnitine; Diabetes Mellitus, Type 2; Drug Synergism; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Inflammation; Insulin Resistance; Lactones; Male; Middle Aged; Obesity; Orlistat

Mean insulin resistance (IR) is greater and it is also more variable in overweight women with polycystic ovarian syndrome (PCOS) compared to weight matched controls. Whilst treatment will reduce the mean IR, it is not known if the IR variability is also reduced.. To compare the change in IR and its variability before and after treatment with insulin sensitization through metformin and pioglitazone, compared to that induced by weight loss with orlistat.. Randomized, open labelled parallel study.. Endocrinology outpatient clinic at a referral centre.. Thirty obese PCOS patients [BMI 36.0 +/- 1.2 kg/m(2) (mean +/- SEM)] participated in the study.. The change in biological variability (BV) was assessed by measuring IR (homeostasis model assessment method) at 4-day intervals on 10 consecutive occasions before and 12 weeks after randomization to metformin, pioglitazone or orlistat.. The primary end point of the study was a change in BV of IR.. Treatment with pioglitazone, orlistat and metformin reduced the overall IR by 41.0 +/- 4.1%, 19.7 +/- 6.4% and 16.1 +/- 6.8% (P = 0.005, P = 0.013, P = 0.17, respectively) and IR variability by 28.5 +/- 18.0%, 41.8 +/- 11.6% and 23.7 +/- 17.0 (P = 0.20, P = 0.015 and P = 0.28, respectively). Free androgen index reduced significantly with all treatments.. Only orlistat reduced both IR and its variability significantly, though all three drugs were effective in reducing hyperandrogenism within the 12-week period of the study.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Female; Humans; Hyperandrogenism; Hypoglycemic Agents; Insulin; Insulin Resistance; Lactones; Metformin; Orlistat; Pioglitazone; Polycystic Ovary Syndrome; Thiazolidinediones; Treatment Outcome

The objective was to investigate in a group of obese subjects the course in skeletal muscle phospholipid (SMPL) fatty acids (FA) during a 24-weeks weight maintenance program, which was preceded by a successful very low calorie dietary intervention (VLCD). Special focus was addressed to SMPL omega-3 FA, which is a lipid entity that influences insulin action.. Nine obese subjects (BMI = 35.7 +/- 1.0 kg/m(2)), who had completed an 8 weeks VLCD (weight-loss = -9.7 +/- 1.6 kg, P < 0.001), had obtained skeletal muscle biopsies (vastus lateralis) before and after a dietician-guided 24-weeks weight-maintenance program (-1.2 +/- 1.5 kg, P = ns). SMPL FA composition was determined by gas liquid chromatography. During the preceding VLCD, insulin sensitivity (HOMA-IR) and glycemic control (HbA1c) improved but no change in SMPL omega-3 FA was observed. During the weight-maintenance program five subjects received the pancreas lipase inhibitor Orlistat 120 mg t.i.d. versus placebo.. HOMA-IR and HbA1c stabilized and SMPL total omega-3 FA, docosahexaenoic acid and ratio of n-3/n-6 polyunsaturated FA increased by 24% (P < 0.01), 35% (P < 0.02) and 26% (P < 0.01), respectively, whereas saturated and monounsaturated FA did not change. Plasma total-cholesterol and LDL-cholesterol, which decreased during the VLCD, reverted to pre-VLCD levels (P < 0.01). Orlistat therapy was associated with weight-loss (P < 0.05), trends for better glycemic control (P = 0.15) and greater increase in SMPL docosahexaenoic acid (P = 0.12) but similar reversal of plasma cholesterols compared to placebo.. The data are consistent with the notion that greater SMPL omega-3 FA obtained during a weight-maintenance program may play a role for preserving insulin sensitivity and glycemic control being generated during a preceding VLCD.

Topics: Body Mass Index; Caloric Restriction; Diet, Reducing; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Enzyme Inhibitors; Fatty Acids; Female; Follow-Up Studies; Humans; Insulin Resistance; Lactones; Lipase; Lipids; Middle Aged; Muscle, Skeletal; Obesity; Orlistat; Phospholipids; Pilot Projects; Triglycerides

To investigate the combined effect of diet and orlistat, for 24 weeks, on anthropometric features, hormonal parameters, and indices of insulin resistance in obese women with polycystic ovary syndrome (PCOS) and in obese women without the syndrome.. Prospective clinical study.. Department of obstetrics and gynecology in a major university in Greece.. Eighteen selected women with PCOS were matched for age and body mass index with 14 obese control women.. Subjects were prescribed an energy-restricted diet, and orlistat (120 mg, 3 times per d) was administered to all subjects for 24 weeks.. At baseline, week 12, and week 24, after an overnight fast, blood samples were collected, and serum levels of FSH, LH, PRL, T, Delta(4)A, DHEAS, 17 alpha-hydroxyprogesterone, sex hormone-binding globulin, glucose, and insulin were measured.. Testosterone levels were significantly decreased with treatment in women with PCOS; this decrease was attributed to the first trimester, whereas T levels did not change during the second 12-week period. In women with PCOS, insulin levels and HOMA-IR values were decreased during the first 12 weeks, whereas no significant change was observed during the second trimester.. Orlistat administration, combined with diet, for 24 weeks, resulted in significant weight loss and improvement of insulin resistance in obese women, with or without PCOS. Moreover, T levels were significantly decreased in women with PCOS. There appears to be a trend during the first 12-week period for greater improvement of metabolic and hormonal parameters in women with PCOS.

Topics: 17-alpha-Hydroxyprogesterone; Androgens; Androstenedione; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Caloric Restriction; Case-Control Studies; Combined Modality Therapy; Dehydroepiandrosterone Sulfate; Female; Follicle Stimulating Hormone; Humans; Insulin; Insulin Resistance; Lactones; Luteinizing Hormone; Obesity; Orlistat; Polycystic Ovary Syndrome; Prolactin; Prospective Studies; Sex Hormone-Binding Globulin; Testosterone; Time Factors; Treatment Outcome; Weight Loss

To assess the impact of weight reduction on serum adipocytokines, C-reactive protein (CRP), and insulin sensitivity in hypertensive female patients with central obesity.. This study was performed using the database and stored serum samples of female patients who had participated in an intervention study focused on weight loss. Thirty hypertensive women aged 18 to 65, body mass index (BMI) > 27 kg/m2, and central obesity were selected. They were randomly assigned to receive either a low-calorie diet plus orlistat 120 mg three times daily or a low-calorie diet alone for 16 weeks. Patients who experienced weight loss greater than 5% (n = 24) were assessed for blood pressure, anthropometric parameters, visceral fat, insulin resistance (HOMA-R - homeostasis model assessment of insulin resistance) and sensitivity (ISI - Insulin Sensitivity Index) indices, plus serum lipids, adipocytokines (adiponectin, leptin, IL-6, and TNF-alpha) and CRP levels.. After BMI had been reduced by approximately 5% in both groups, visceral fat, fasting glucose, triglycerides, and TNF-alpha decreased. Only the orlistat group, which was more insulin resistant at baseline, showed a significant reduction in blood glucose after oral glucose load, in addition to increased insulin sensitivity.. This study's findings indicate that a weight loss greater than 5% is associated with improved inflammatory status and decreased insulin resistance, regardless of changes in adiponectin and TNF-a levels. The greatest improvements in insulin sensitivity experienced by the orlistat-treated patients could not be attributed to the use of this drug because of the higher number of insulin-resistant subjects in this group.

Topics: Adipokines; Adiponectin; Adolescent; Adult; Aged; Anti-Obesity Agents; Blood Glucose; Body Mass Index; C-Reactive Protein; Chi-Square Distribution; Diet, Reducing; Female; Humans; Hypertension; Insulin Resistance; Lactones; Lipids; Middle Aged; Obesity; Orlistat; Tumor Necrosis Factor-alpha; Waist-Hip Ratio; Weight Loss

To specify changes in clinicolaboratory parameters in reduction of obesity in patients with diabetes mellitus type 2 (DM-2).. Antropometry, densitometry of fat tissue (FT) were made and parameters of fat and carbohydrate metabolism (lipidogram, glycated hemoglobin, immunoreactive insulin), FT secretory activity (leptin, adiponectin, TNF-alpha) were studied in 75 obese DM-2 patients. After the above primary examination all the patients were randomized into 2 groups: group 1 (n = 55) received xenical (120 mg 3 times a day) and kept moderate hypocaloric diet; group 2 (n = 20) received only the above diet therapy. Active treatment lasted 24 weeks.. In addition to symptoms of metabolic syndrome (MS) the patients were found to have secretory disturbances of FT activity: elevation of leptin and TNF-alpha levels, subnormal adiponectin. These alterations directly correlated with body mass, FT mass gain, increase in waist circumference. Hyperleptinemia, hyperinsulinemia and hypoadiponectinemia were considered as markers of insulin resistance (IR) and related conditions. Xenical promoted a significant weight loss resulting in a positive trend in the parameters of adipokines, fat and carbohydrate metabolism, in reduction of IR.. Xenical is beneficial for patients with DM-2 and obesity because it improves metabolic processes.

Topics: Adiponectin; Adipose Tissue; Anthropometry; Anti-Obesity Agents; Biomarkers; Body Weight; Caloric Restriction; Carbohydrate Metabolism; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Lactones; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Tumor Necrosis Factor-alpha

The objective of this study was to evaluate and compare the effect of treatment with orlistat vs. metformin on the hormonal and biochemical features of patients with polycystic ovarian syndrome (PCOS). Twenty-one Caucasian women with PCOS [mean (+/-SEM) age 27 +/- 0.9 yr and body mass index 36.7 +/- 3.3 kg/m(2)] participated in this prospective, randomized, open-labeled study. All subjects had an 8-wk run-in period of dietary modification and then randomized to receive either metformin (500 mg three times daily) or orlistat (120 mg three times daily) for 3 months. Weight, blood pressure, and fasting blood samples were taken at screening, randomization, and on completion. Insulin resistance (IR) was calculated using the homeostasis model of assessment (HOMA)-IR method [HOMA-IR = (insulin x glucose)/22.5]. The results are expressed as mean +/- SEM. When compared with baseline, treatment with both orlistat [93.5 +/- 11.5 ng/dl (3.24 +/- 0.4 nmol/liter) vs. 114.5 +/- 11.5 ng/dl (3.97 +/- 0.4 nmol/liter), P = 0.039] and metformin [97.2 +/- 11.5 ng/dl (3.37 +/- 0.4 nmol/liter) vs. 120.0 +/- 8.7 ng/dl (4.16 +/- 0.3 nmol/liter), P = 0.048] produced a significant reduction in total testosterone. Treatment with orlistat produced a 4.69% reduction in weight (99.0 +/- 6.0 vs. 94.6 +/- 6.1 kg, P = 0.002), and this reduction was more significant than the reduction produced by metformin (4.69 vs. 1.02%, P = 0.006). There was no significant reduction seen after either treatment group for fasting insulin, HOMA-IR, SHBG, or any of the lipid parameters studied. In this study, orlistat produced a significant reduction in weight and total testosterone. The reduction in total testosterone was similar to that seen after treatment with metformin. Therefore, orlistat may prove to be a useful adjunct in the treatment of PCOS.

Topics: Adult; Blood Pressure; Body Mass Index; Body Weight; Cholesterol; Enzyme Inhibitors; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Lactones; Lipoproteins; Metformin; Orlistat; Polycystic Ovary Syndrome; Testosterone; Weight Loss; White People

To study effects of body mass loss due to orlistat on carbohydrate and lipid metabolism, insulin resistance, 24-h profile of arterial pressure (AP), left ventricular myocardial hypertrophy, brain perfusion in patients with metabolic syndrome (MS).. Thirty middle-aged patients with MS entered the trial. They received orlistat in a dose 120 mg twice a day for 24 weeks. Before and after the treatment the patients' carbohydrate and lipid metabolism, insulin resistance were studied, 24-h monitoring of arterial pressure, echo-cardiography were made. Brain perfusion was studied with single-photon emission computed tomography in 18 patients. Results. All the patients lost much weight. This was accompanied with improved indices of AP profile, metabolism of carbohydrates and lipids, insulin resistance, left ventricular hypertrophy, brain perfusion. Conclusion. Orlistat treatment weakens basic factors of cardiovascular risk.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Cardiovascular Diseases; Cerebral Angiography; Female; Humans; Insulin; Insulin Resistance; Lactones; Lipid Metabolism; Lipids; Male; Metabolic Syndrome; Orlistat; Risk Factors; Weight Loss

Dietary fat has been reported to influence insulin sensitivity.. The objective of the study was to determine how identical weight loss (target: loss of 8% of body weight over 3-6 mo) in women taking orlistat or placebo combined with a hypocaloric diet influences body composition and insulin sensitivity.. Forty-seven obese women [body mass index (in kg/m(2)): 32.1 +/- 0.4] were randomly assigned to receive either orlistat (120 mg 3 times daily; n = 23) or placebo (n = 24) with a hypocaloric diet. Whole-body insulin sensitivity (insulin clamp technique), serum fatty acids, and body composition (magnetic resonance imaging) were measured before and after weight loss.. The groups did not differ significantly at baseline with respect to age, body weight, intraabdominal and subcutaneous fat volumes, or insulin sensitivity. Weight loss did not differ significantly between the orlistat (7.3 +/- 0.2 kg, or 8.3 +/- 0.1%) and placebo (7.4 +/- 0.2 kg, or 8.2 +/- 0.1%) groups. Insulin sensitivity improved significantly (P < 0.001) and similarly after weight loss in the orlistat (from 4.0 +/- 0.3 to 5.1 +/- 0.3 mg x kg fat-free mass(-1) x min(-1)) and placebo (from 4.4 +/- 0.4 to 5.4 +/- 0.4 mg x kg fat-free mass(-1) x min(-1)) groups. Intraabdominal fat and subcutaneous fat decreased significantly in both groups, but the ratio of the 2 decreased significantly only in the orlistat group. The proportion of dihomo-gamma-linolenic acid (20:3n-6) in serum phospholipids was inversely related to insulin sensitivity both before (r = -0.48, P < 0.001) and after (r = -0.46, P < 0.001) weight loss, but it did not change significantly in either group.. Weight loss rather than inhibition of fat absorption enhances insulin sensitivity. A decrease in fat absorption by orlistat appears to favorably influence the ratio between intraabdominal and subcutaneous fat, which suggests that exogenous fat or its composition influences fat distribution.

Topics: Adult; Anti-Obesity Agents; Blood Pressure; Body Mass Index; Diet, Reducing; Dietary Fats; Fatty Acids; Female; Humans; Insulin Resistance; Lactones; Middle Aged; Obesity; Orlistat; Weight Loss

Moderate weight loss is recommended for overweight and obese patients with type 2 diabetes, and conjunctive use of weight loss medication has been advocated. The current study examined weight loss-dependent and -independent effects of the intestinal lipase inhibitor orlistat at 6 months of treatment, using behavioral intervention (Int) combined with randomized, double-blinded, placebo (P)-controlled treatment with orlistat (O).. Metabolic control, insulin sensitivity (IS), regional fat distribution, and fat content in liver and muscle were measured in 39 volunteers with type 2 diabetes in whom all antidiabetic medication was withdrawn 1 month preceding randomization. Weight loss was equivalent in the Int+O and Int+P groups, respectively (-10.3 +/- 1.3 vs. -8.9 +/- 1.1%), and there were identical decreases in visceral adipose tissue (VAT), fat mass (FM), thigh adiposity, and hepatic steatosis.. Weight loss resulted in substantial improvement (P < 0.001) in HbA(1c) (-1.6 +/- 0.3 vs. -1.0 +/- 0.4%; NS between groups). IS improved significantly more with orlistat (Delta2.2 +/- 0.4 vs. Delta1.2 +/- 0.4 mg. min(-1). kg(-1) fat-free mass [FFM]; P < 0.05), and plasma free fatty acid (FFA) levels were strongly correlated with IS (r = 0.56; P < 0.001). Orlistat caused greater reductions in fasting plasma FFA (Delta-154 +/- 22 vs. Delta-51 +/- 33 micro mol/l; P < 0.05), insulin-suppressed FFA (Delta-119 +/- 23 vs. Delta-87 +/- 34 micro mol/l; P < 0.05), and fasting plasma glucose (FPG; -62 +/- 9 vs. -32 +/- 8 mg/dl; P = 0.02). Changes in HbA(1c) were correlated with DeltaIS (r = -0.41; P < 0.01) but not with weight loss per se.. At equivalent weight loss, conjunctive use of orlistat resulted in greater improvement in FFA levels and IS.

Topics: Adipose Tissue; Blood Glucose; Body Composition; Body Mass Index; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Glucose; Humans; Hypoglycemic Agents; Insulin Resistance; Lactones; Obesity; Orlistat; Placebos; Time Factors; Weight Loss

This pilot study compared the efficacy of orlistat as an adjunctive treatment for obesity between African American and Caucasian adolescents. Twenty obese adolescents with obesity-related co-morbid conditions underwent measurements of body composition, glucose homeostasis by frequently sampled intravenous glucose tolerance test (FSIGT), and fasting lipids before and after 6 months treatment with orlistat 120 mg tid in conjunction with a comprehensive behavioral program. Weight (p < 0.05), BMI (p < 0.001), total cholesterol (p < 0.001), LDL cholesterol (p < 0.001), fasting insulin (p < 0.02) and fasting glucose (p < 0.003) were lower after treatment. Insulin sensitivity, measured during the FSIGT, improved significantly (p < 0.02), as did fasting indices such as the homeostasis model assessment for insulin resistance (p < 0.01). African American subjects exhibited significantly less improvement in weight (p < 0.05), BMI (p < 0.01), waist circumference (p = 0.03), and insulin sensitivity (p = 0.05). Improvements in cholesterol were not significantly different between African Americans and Caucasians. We conclude that Caucasians lost more weight and had greater improvements in insulin sensitivity than African Americans, but both exhibited improvements in plasma lipids. The true benefit of orlistat treatment over a comprehensive behavioral program remains to be determined in placebo-controlled trials.

Topics: Administration, Oral; Adolescent; Behavior Therapy; Black or African American; Blood Glucose; Body Weight; Capsules; Cholesterol, LDL; Clinical Trials as Topic; Comorbidity; Drug Administration Schedule; Energy Metabolism; Female; Humans; Insulin Resistance; Lactones; Leptin; Male; Obesity; Orlistat; Pilot Projects; Treatment Outcome; White People

Orlistat and metformin are the currently used drugs for weight loss. We aimed to compare the effect of orlistat and orlistat plus metformin combination therapy on weight loss and insulin resistance in obese women.. In all, 57 obese women (body mass index >/=30 kg/m(2) and normal glucose tolerance) were included. All subjects took the same content and caloric diet therapy during the study. After a month of diet period, each individual was randomly assigned to receive 360 mg orlistat per day (group 1; n=30) or 360 mg orlistat plus 1700 mg metformin per day (group 2; n=27) during the next 3 months. Body weight and insulin resistance by the homeostasis model assessment model (HOMA-IR) was measured at baseline, first month and fourth month.. The mean weight loss in groups 1 and 2 was 1.36+/-0.8 kg (1.4+/-0.7%) and 1.11+/-0.7 kg (1.1+/-0.7%) from baseline to first month; 4.8+/-2.9 kg (5.28+/-3.0%) and 5.77+/-2.5 kg (6.17+/-2.9%) from first month to fourth month. Body weight was decreased in groups 1 (P< 0.001) and 2 (P< 0.001), but there was no statistically significant difference between groups. Change of HOMA-IR in groups 1 and 2 was 0.41+/-0.4 (14.9+/-10.1%) and 0.23+/-0.7 (8.16+/-12.3%) from baseline to first month; 0.49+/-0.77 (22.0+/-26%) and 0.95+/-0.88 (34.8+/-29.1%) from first month to fourth month. HOMA-IR value was decreased in groups 1 (P< 0.001) and 2 (P< 0.001) but was not different between groups during the study period.. Combination of orlistat with metformin did not result in an additional effect on weight loss and insulin resistance when compared to orlistat alone in our study. However, new studies which have more sample sizes and the longer study period are necessary for this purpose.

Topics: Adult; Dietary Fats; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Intestinal Absorption; Lactones; Lipase; Metformin; Middle Aged; Obesity; Orlistat; Prospective Studies; Statistics, Nonparametric

Non-alcoholic steatohepatitis (NASH) is frequent in obese subjects and has a relatively benign course; however, it may progress to cirrhosis. Weight loss in these patients may alleviate the findings of NASH. The aim of this study was to investigate the effects of pharmacological anti-obesity therapies on the findings of NASH.. There were thirteen patients (9 women, 4 men) in sibutramine group and 12 patients (8 women, 4 men) in orlistat group. The mean ages and body-mass indexes of the two groups were 42.5 years, 37.3 kg/m2 and 43.2 years, 36.1 kg/m2, respectively.. The obese subjects with NASH were given sibutramine or orlistat for six months. Additionally, all patients were given a low caloric diet. Liver enzymes (AST, ALT, GGT and ALP), insulin resistance (analysed by HOMA) and hepatic ultrasound (US) findings were assessed at baseline and after 6 months.. Both sibutramine and orlistat significantly reduced body weight (10.2 and 8.4%, respectively), insulin resistance (47 and 40%, respectively), AST (41 and 39%, respectively), ALT (59 and 58%, respectively), and GGT serum levels (27 and 25%, respectively). The ultrasonographic regression in steatosis was observed in 11 patients who received sibutramine and 8 patients who received orlistat. During the treatment, unexpectedly significant increases in total alkaline phosphatase levels were found in both sibutramine and orlistat groups (9 and 14%, respectively).. The present study shows that both sibutramine-induced and orlistat-induced weight losses result in reduction of insulin resistance, and improvements in biochemical markers and US findings of NASH. Because the GGT levels decreased in both groups, the increased ALP levels might have another source.

Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Enzyme Inhibitors; Fatty Liver; Female; Humans; Insulin Resistance; Lactones; Lipase; Liver; Male; Obesity; Orlistat; Ultrasonography; Weight Loss

We examined the weight-losing effect of orlistat treatment on insulin sensitivity and cardiovascular risk factors in a group of severely obese young Chinese patients with or without type 2 diabetes mellitus.. Obese patients with diabetes (n = 33) and obese nondiabetic patients (n = 27) were given orlistat, 120 mg 3 times daily, without a concomitant hypocaloric diet for 6 months (body mass index [calculated as weight in kilograms divided by the square of height in meter; kg/m2] range, 27.8-47.4). The efficacy measures were (1) insulin sensitivity indices derived from the homeostasis model assessment and a composite measure of whole-body insulin sensitivity index; (2) glycemic control; (3) cardiovascular risk factors, including anthropometry, blood pressure, lipid profiles, and albuminuria; and (4) body composition determined by dual-energy x-ray absorptiometry.. At baseline, patients with diabetes had lower body mass index and percentage of body fat but higher waist-hip ratios and were more insulin resistant. Orlistat therapy reduced body weight, waist and hip circumferences, percentage of total body fat, blood pressure, fasting plasma glucose and lipid levels, albuminuria, and insulin sensitivity indices in both groups (all, P<.05). Despite less weight reduction, we found a greater percentage of reduction from baseline in glycosylated hemoglobin level (-11.6% vs -3.6%; P<.001), fasting plasma glucose level (-18.2% vs -5.0%; P<.001), and systolic blood pressure (-7.1% vs -3.1%; P =.02) in patients with diabetes. Obese subjects without diabetes had greater improvements in triglyceride levels, albuminuria, and the homeostasis model assessment (all, P<.01).. Short-term orlistat treatment without the use of a hypocaloric diet significantly improved insulin sensitivity and cardiovascular risk profiles in severely obese Chinese patients with or without type 2 diabetes.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Body Composition; Body Constitution; Body Mass Index; Cardiovascular Diseases; China; Diabetes Mellitus, Type 2; Diet, Reducing; Energy Intake; Female; Hong Kong; Humans; Insulin Resistance; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat; Outpatients; Prospective Studies; Quality of Life; Risk Factors; Time Factors; Weight Loss

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

Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. Promoting the browning of white adipose tissue has been suggested as a potential strategy, but a drug still needs to be identified. Here, genetic deletion of activating transcription factor 3 (

Topics: 3T3-L1 Cells; Activating Transcription Factor 3; Adipocytes, Brown; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Anti-Obesity Agents; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Body Temperature Regulation; Diet, High-Fat; Disease Models, Animal; Humans; Insulin Resistance; Lipogenesis; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Orlistat; Plant Extracts; Plants, Medicinal; Salvia miltiorrhiza

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

The aim of this study was to evaluate the effect of orlistat or metformin combined with Diane-35 on anthropometric, hormonal and metabolic parameters in overweight and obese polycystic ovary syndrome (PCOS) patients with insulin resistance (fasting insulin > 10 mIU/L). A total of 240 PCOS women were randomly allocated to orlistat plus Diane-35(OD group), metformin plus Diane-35(MD group), orlistat plus metformin plus Diane-35(OMD group) or Diane-35 (D group). Body weight, BMI, waist and hip circumference, blood pressure, endocrine profile, lipid profile and insulin resistance were assessed at baseline and after 3 months. Significant reductions in waist and hip circumference, serum LH, total testosterone and uric acid were observed in all groups compared with baseline. TG and TC significantly decreased in the OD group. Homeostasis model assessment insulin resistance (HOMA-IR) index was reduced in the OD (p = .015), MD (p = .001) and OMD (p = .004) groups. Body weight, BMI, systolic BP and HDL-C significantly changed in the OD and OMD group compared with the D group (p < .05). Side effects were less with orlistat than metformin. This study demonstrated that orlistat is more effective in reducing weight and lipid profile than metformin. Besides, orlistat has mild side-effects and is better tolerated compared with metformin.

Topics: Adult; Anti-Obesity Agents; Cyproterone Acetate; Drug Combinations; Drug Therapy, Combination; Ethinyl Estradiol; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Lactones; Metformin; Obesity; Orlistat; Overweight; Polycystic Ovary Syndrome; Young Adult

Adiponectin and chemerin have been reported their associations with insulin resistance and chronic inflammation. However, the relationship between adiponectin and chemerin themselves has not been fully elucidated. Therefore, we investigated the effects of changes in adiponectin and chemerin levels after a weight intervention.. We recruited 136 healthy overweight or obese subjects from 2006 to 2009 and provided all participants lifestyle modification therapy with diet consultations over 16 weeks. We assigned the participants to take orlistat or sibutramine or to a no prescription group. We analyzed the data using paired t-tests, Pearson's partial correlation analysis, and stepwise multiple linear regression analysis.. ∆ in chemerin was positively correlated with ∆ in adiponectin (r = 0.29, p < 0.01), and these trends were similar in the insulin-resistant (r = 0.35, p = 0.03) and insulin-sensitive (r = 0.27, p < 0.01) groups. In multiple regression analyses, Δadiponectin, ΔQUICKI (quantitative insulin-sensitivity check index), Δglucose, and ΔDBP were significantly associated with Δchemerin in the insulin-resistant group, and initial chemerin level, ΔQUICKI, ΔBMI (body mass index), and taking orlistat were associated with Δchemerin in the insulin-sensitive group.. Changes in chemerin levels were positively associated with changes in adiponectin levels. The association between these changes might be related to chemerin's dual inflammatory and anti-inflammatory effects or insulin resistance and insulin sensitivity enhancing effects, depending on the metabolic conditions. Additional studies are needed to clarify the mechanisms that underlie the effects of adiponectin and chemerin.

Topics: Adiponectin; Adult; Anti-Obesity Agents; Appetite Depressants; Biomarkers; Body Mass Index; Chemokines; Combined Modality Therapy; Cyclobutanes; Diet, Reducing; Exercise; Female; Healthy Lifestyle; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Lactones; Male; Middle Aged; Obesity; Orlistat; Overweight; Waist Circumference; Weight Loss

Obesity-related insulin resistance is linked to a chronic state of systemic and adipose tissue-derived inflammation. Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone also acting on adipocytes. We investigated whether GIP affects inflammation, lipolysis, and insulin resistance in human adipocytes. Human subcutaneous preadipocyte-derived adipocytes, differentiated in vitro, were treated with human GIP to analyze mRNA expression and protein secretion of cytokines, glycerol, and free fatty acid release and insulin-induced glucose uptake. GIP induced mRNA expression of IL-6, IL-1β, and the IL-1 receptor antagonist IL-1Ra, whereas TNFα, IL-8, and monocyte chemotactic protein (MCP)-1 remained unchanged. Cytokine induction involved PKA and the NF-κB pathway as well as an autocrine IL-1 effect. Furthermore, GIP potentiated IL-6 and IL-1Ra secretion in the presence of LPS, IL-1β, and TNFα. GIP induced lipolysis via activation of hormone-sensitive lipase and was linked to NF-κB activation. Finally, chronic GIP treatment impaired insulin-induced glucose uptake possibly due to the observed impaired translocation of glucose transporter GLUT4. In conclusion, GIP induces an inflammatory and prolipolytic response via the PKA -NF-κB-IL-1 pathway and impairs insulin sensitivity of glucose uptake in human adipocytes.

Topics: Adipocytes; Adult; Anti-Obesity Agents; Cyclic AMP-Dependent Protein Kinases; Cytokines; Gastric Inhibitory Polypeptide; Humans; Insulin Resistance; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Interleukin-6; Lactones; Lipolysis; Middle Aged; NF-kappa B; Orlistat; Signal Transduction; Up-Regulation

To assess the effects of weight loss on serum adipokine levels in polycystic ovary syndrome (PCOS).. We determined serum leptin, adiponectin, resistin, and visfatin levels in 60 overweight/obese women with PCOS and 48 BMI-matched female volunteers. Measurements were repeated after 24 weeks of treatment with orlistat 120 mg 3 times per day along with an energy-restricted diet.. At baseline, serum visfatin concentration was higher in patients with PCOS than in controls (p = 0.036); serum levels of leptin, adiponectin, and resistin did not differ between the two groups. After 24 weeks, a significant reduction in BMI and waist circumference was observed in both patients with PCOS and controls (p < 0.001 vs. baseline in both groups). Also serum leptin levels decreased in both patients with PCOS and controls (p < 0.001 vs. baseline in both groups). The reduction in serum leptin levels did not differ between groups. Serum adiponectin, resistin, and visfatin levels did not change in either group.. Leptin, adiponectin, and resistin do not appear to play major pathogenetic roles in overweight/obese patients with PCOS. In contrast, visfatin emerges as a potentially important mediator of the endocrine abnormalities of these patients. However, serum visfatin levels are not substantially affected by weight loss.

Topics: Adipokines; Adiponectin; Adult; Anti-Obesity Agents; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hyperandrogenism; Insulin Resistance; Lactones; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Orlistat; Polycystic Ovary Syndrome; Resistin; Waist Circumference; Weight Loss; Young Adult

To assess the efficacy of a specific long-term programme for weight loss maintenance using a new 'on/off' Orlistat approach in obese subjects who previously lost more than 10% of their body weight.. 50 patients were followed up during 4 years; 34 completed the study. Subjects were followed up by physicians trained in obesity management. Anthropometrical, biological and psychological parameters were measured. Insulin sensitivity was evaluated by euglycaemic insulin clamp. Orlistat was given in case of weight relapse more than 2.5%. Subjects could take Orlistat on a voluntary basis for special occasions.. The BMI of completers remained stable (29.5 ± 0.9 vs. 30.6 ± 1.0 kg/m(2)). 73% of completers maintained 10% or more of their weight loss. Subjects from the no-regain group improved most of their parameters while the regain group did not. Insulin sensitivity was negatively linked to body weight during the follow up (p < 0.01, r(2) = 0.20). A negative relationship has been found between extent of the previous weight loss and the evolution of body weight during the 4 years follow-up (p < 0.01, r(2) = 0.26). Orlistat intake showed a body fat lowering effect (p < 0.05).. 73% of subjects maintained more than 10% of their weight loss. Subject with a large weight loss amount are at high risk for weight regain. The Orlistat 'on/off' intake regarding his lowering body fat mass effect seems to be efficient.

Topics: Adipose Tissue; Adult; Anti-Obesity Agents; Body Mass Index; Female; Follow-Up Studies; Humans; Insulin Resistance; Lactones; Male; Obesity; Orlistat; Recurrence; Treatment Outcome; Weight Gain; Weight Loss

The aim of this study was to determine the role of fatty acid signalling in islet beta cell compensation for insulin resistance in the Zucker fatty fa/fa (ZF) rat, a genetic model of severe obesity, hyperlipidaemia and insulin resistance that does not develop diabetes.. NEFA augmentation of insulin secretion and fatty acid metabolism were studied in isolated islets from ZF and Zucker lean (ZL) control rats.. Exogenous palmitate markedly potentiated glucose-stimulated insulin secretion (GSIS) in ZF islets, allowing robust secretion at physiological glucose levels (5-8 mmol/l). Exogenous palmitate also synergised with glucagon-like peptide-1 and the cyclic AMP-raising agent forskolin to enhance GSIS in ZF islets only. In assessing islet fatty acid metabolism, we found increased glucose-responsive palmitate esterification and lipolysis processes in ZF islets, suggestive of enhanced triglyceride-fatty acid cycling. Interruption of glucose-stimulated lipolysis by the lipase inhibitor Orlistat (tetrahydrolipstatin) blunted palmitate-augmented GSIS in ZF islets. Fatty acid oxidation was also higher at intermediate glucose levels in ZF islets and steatotic triglyceride accumulation was absent.. The results highlight the potential importance of NEFA and glucoincretin enhancement of insulin secretion in beta cell compensation for insulin resistance. We propose that coordinated glucose-responsive fatty acid esterification and lipolysis processes, suggestive of triglyceride-fatty acid cycling, play a role in the coupling mechanisms of glucose-induced insulin secretion as well as in beta cell compensation and the hypersecretion of insulin in obesity.

Topics: Animals; Binding Sites; Colforsin; Fatty Acids, Nonesterified; Gene Expression Regulation; Glucagon-Like Peptide 1; Glucose; In Vitro Techniques; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Islets of Langerhans; Lactones; Lipase; Lipid Metabolism; Lipolysis; Models, Biological; Orlistat; Oxidation-Reduction; Rats; Rats, Zucker; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction

To study effects of xenical combined with moderately hypocaloric diet on fat tissue mass, carbohydrate and lipid metabolism in patients with metabolic syndrome.. The study included 60 patients with body mass index (BMI) over 30 kg/m2, mild and moderate arterial hypertension, dyslipidemia, impaired glucose tolerance (IGT) and diabetes mellitus (DM) type 2. The patients were divided into two groups. 30 patients of group 1 received xenical in a dose 120 mg 3 times a day for 24 weeks. 30 patients of the control group received only the above diet for 24 weeks. The examination included 24-h monitoring of arterial pressure, anthropometric measurements, tests for glycemia, C-peptide, cholesterol, triglycerides (TG), LDLP, HDLP.. Group 1 patients reduced their weight by 10.8 +/- 7.5 kg and fat tissue mass by 9.4 +/- 9.2 kg. This was in correlation with improvement of fatty, carbohydrate metabolism, arterial pressure. After 24 weeks of therapy xenical lowered cholesterol by 15%, LDLP cholesterol by 20%, TG by 28%, systolic and diastolic pressure by 5 and 4%.. Combination of xenical with hypocaloric diet can be used in therapy of patients with metabolic syndrome.

Topics: Anti-Obesity Agents; Blood Pressure; Body Weights and Measures; Female; Humans; Insulin Resistance; Lactones; Lipids; Male; Obesity; Orlistat; Treatment Outcome

The study was undertaken to examine the nature and degree of postprandial lipemia during routine food fat loading (FFL) in young obese patients and the possible ways of correcting excessive body mass (BM) and hormonally metabolic disturbances. Fifty obese patients aged 18 to 25 years were examined. Group 1 comprised 20 patients with the BM index (BMI) of 33.4 +/- 0.8 kg/m2; Group 2 included 30 patients with the BMI of 33.05 +/- 5.22 kg/m2. The conventional glucose tolerance test was performed in all the examinees, by determining the degree of glycemia, the levels of immunoreactive insulin, and the insulin-resistance index (IRI). With FFL, lipid profile trends were studied in Group 1 patients. Before and 6 months after xenical therapy, anthropometric, lipid and carbohydrate metabolic parameters were determined and BMI was calculated in Group 2 patients. Group 1 patients were found to have impaired tolerance to FFL as compared with the control group. Postalimentary lipemia was accompanied by atherogenic changes in hormonally metabolic parameters. During xenical therapy, Group 2 patients were found to have positive changes in all anthropometric parameters, including those characterizing abdominal obesity, as well as normalized basal hyperinsulinemia, diminished stimulated insulinemia, increased insulin sensitivity, improved blood lipid profile with decreased atherogenic changes. Thus, the study has revealed that young obese patients show impaired fat tolerance with normal glucose tolerance. For therapy of obesity in young individuals, xenical may be recommended as an agent that not only decreases BM, but also improves hormonally metabolic parameters.

Topics: Adolescent; Adult; Anti-Obesity Agents; Body Mass Index; Dietary Fats; Female; Humans; Insulin Resistance; Lactones; Male; Obesity; Orlistat; Risk Factors