orlistat and Non-alcoholic-Fatty-Liver-Disease

Obesity is closely associated with nonalcoholic fatty liver disease (NAFLD), a highly prevalent disease without any approved medication. The aim of this review was to summarize the evidence on the effect of anti-obesity medications on NAFLD, especially focusing on hepatic histology.. Orlistat and some glucagon-like peptide-1 receptor analogs, including liraglutide and semaglutide, have beneficial effects on hepatic steatosis and inflammation, but not fibrosis. Other anti-obesity medications, including lorcaserin, setmelanotide, phentermine hydrochloric, phentermine/topiramate, and naltrexone/bupropion, have been minimally investigated in NAFLD. Furthermore, medications like sodium-glucose cotransporter-2 inhibitors and farnesoid X receptor have shown beneficial effects in both NAFLD and obesity, but they have not been licensed for either disease. Liraglutide, semaglutide, and orlistat may be currently used in selected patients with obesity and NAFLD. Further research is warranted, since targeting obesity may provide additional benefits on its comorbidities, including NAFLD.

Topics: Anti-Obesity Agents; Humans; Liraglutide; Non-alcoholic Fatty Liver Disease; Obesity; Orlistat; Phentermine; Sodium-Glucose Transporter 2 Inhibitors

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 in adolescents presents many challenges for the patient, family, and physician. The myriad problems involving the GI tract will be managed more effectively when the treating physician has an understanding of the presentations, pathophysiology, appropriate laboratory evaluation, and approaches to treatment for these complications. In addition to being familiar with the pharmacotherapeutic options available, having an approach to behavioral change, such as MI, can be an extremely useful tool.

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Anti-Obesity Agents; Constipation; Contraceptives, Oral, Combined; Diabetes Mellitus, Type 2; Digestive System Diseases; Fecal Incontinence; Gallstones; Gastroesophageal Reflux; Humans; Hypoglycemic Agents; Lactones; Metformin; Non-alcoholic Fatty Liver Disease; Orlistat; Pancreatitis; Pediatric Obesity

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term, which encompasses simple steatosis and non-alcoholic steatohepatitis (NASH). The entire spectrum of NAFLD has been associated with metabolic syndrome. NASH is associated with increased mortality compared with that of the general population. Many therapeutic options for NASH have been studied. However, there is very little evidence supporting the efficacy of most regimens for the treatment of NASH.. To provide a review focusing on the current therapeutic options available for patients with NASH as well as to briefly introduce possible future interventions.. A MEDLINE, Pubmed and Cochrane Review database search using a combination of keywords, which included non-alcoholic fatty liver disease, non-alcoholic hepatic steatosis, NAFLD, NASH, treatment, therapeutics, vitamin E, orlistat and bariatric surgery. An overall summary of the articles was developed for each section of discussion in this review.. NASH associated with metabolic syndrome can progress advanced fibrosis and cirrhosis. Weight loss and lifestyle modification have been shown to improve NASH. Other medications used for weight loss and metabolic syndrome have been evaluated, such as orlistat, metformin and thiazolidinediones. Alternative regimens using ursodeoxycholic acid, statins and probiotics as well as bariatric surgery have been evaluated, but have not been recommended as first-line treatment for NASH. Vitamin E for NASH patients without diabetes seems to be promising. The lack of effective treatment for NASH suggests the heterogeneity of patients presenting with the NASH phenotype. The best treatment strategy for these patients may be to identify their pathogenic target and develop personalised treatment protocols.. Currently, there are few options available for the management of NASH. Future targeted treatment strategies based on the pathogenic pathways may be needed to develop effective treatment for patients with NASH.

Topics: Bariatric Surgery; Fatty Liver; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lactones; Metabolic Syndrome; Metformin; Non-alcoholic Fatty Liver Disease; Orlistat; Precision Medicine; Thiazolidinediones; Ursodeoxycholic Acid; Vitamin E; 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

Non-alcoholic fatty liver disease (NAFLD) is becoming a wide spread liver disease. The present recommendations for treatment are not evidence-based. Some of them are various weight reduction measures with diet, exercise, drug, or surgical therapy.. To assess the benefits and harms of intended weight reduction for patients with NAFLD.. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, PubMed, EMBASE, Science Citation Index Expanded, Chinese Biomedicine Database, and ClinicalTrials.gov until February 2011.. We included randomised clinical trials evaluating weight reduction with different measures versus no intervention or placebo in NAFLD patients.. We extracted data independently. We calculated the odds ratio (OR) for dichotomous data and calculated the mean difference (MD) for continuous data, both with 95% confidence intervals (CI).. The review includes seven trials; five on aspects of lifestyle changes (eg, diet, physical exercise) and two on treatment with a weight reduction drug 'orlistat'. In total, 373 participants were enrolled, and the duration of the trials ranged from 1 month to 1 year. Only one trial on lifestyle programme was judged to be of low risk of bias. We could not perform meta-analyses for the main outcomes as they were either not reported or there were insufficient number of trials for each outcome to be meta-analysed. We could meta-analyse the available data for body weight and body mass index only. Adverse events were poorly reported.. The sparse data and high risk of bias preclude us from drawing any definite conclusion on lifestyle programme or orlistat for treatment of NAFLD. Further randomised clinical trials with low risk of bias are needed to test the beneficial and harmful effects of weight reduction for NAFLD patients. The long-term prognosis of development of fibrosis, mortality, and quality of life should be studied.

Topics: Anti-Obesity Agents; Body Mass Index; Diet, Reducing; Exercise; Fatty Liver; Humans; Lactones; Life Style; Non-alcoholic Fatty Liver Disease; Orlistat; Randomized Controlled Trials as Topic; Weight Loss

One of the important inducers of inflammatory responses and accumulation of fat in hepatocytes is free fatty acids which ultimately lead to the development of non-alcoholic fatty liver disease. Patients with non-alcoholic fatty liver disease have high levels of plasma free fatty acids which are usually associated with type 2 diabetes and components of metabolic syndrome including dyslipidemia. Objective of this research is to investigate the effects of orlistat (a lipase enzyme inhibitor) or telmisartan (an angiotensin receptor blocker) on the serum free fatty acids in non-alcoholic fatty liver disease patients taking into consideration the baseline lipid profile.. This open-label clinical trial was carried out in the Department of Pharmacology, College of Medicine at the University of Sulaimani in cooperation with Shar Teaching Hospital in Sulaimani city-Kurdistan Region of Iraq. A total number of 74 non-alcoholic fatty liver disease patients were recruited and grouped randomly into group I (n = 25) treated with orlistat (120 mg/day orally) for 12 weeks, group II (n = 24) treated with telmisartan (20 mg/day orally) for 8 weeks, and group III (n = 25) treated with placebo (carboxy- methyl cellulose) once daily. Fasting serum level of free fatty acid and lipid profile including total cholesterol, triglyceride, high-density lipoprotein, and non-high-density lipoproteins were determined.. Orlistat and telmisartan significantly reduced the triglyceride-glucose index and free fatty acid levels (P < .001) in patients with non-alcoholic fatty liver diseases.. Short-term treatment with orlistat or telmisartan produce effective and significant reductions in FFAs in patients with non-alcoholic fatty liver disease compared to placebo. Orlistat effectively reduces the free fatty acid irrespective of the baseline lipid profile.

Topics: Diabetes Mellitus, Type 2; Double-Blind Method; Fatty Acids, Nonesterified; Humans; Non-alcoholic Fatty Liver Disease; Orlistat; Telmisartan; Triglycerides

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

Obesity is an abnormal fat accumulation disorder in the metabolic syndrome constellation, and a risk factor for diabetes, cardiovascular disorders, non-alcoholic fatty liver disease (NAFLD), and cancer. Nuclear receptors (Peroxisome proliferator-activated receptor, PPAR) are implicated in metabolic syndrome and NAFLD, and have potential for therapeutic targeting. Nuclear receptors are ligand-dependent transcription factors that have diverse roles in metabolism, including regulating genes involved in lipid and glucose metabolism, modulating inflammatory genes, and are crucial for maintaining metabolic flexibility. PPAR activates adipose triglyceride lipase, which then releases fatty acids as ligands for PPAR, indicating the interdependency of nuclear receptors and lipases. Here, molecular docking was performed with selected phytochemical ligands that can bind with PPAR-α/γ (PDB ID: 2ZNN and 2ATH, respectively) using Glide module of Schrodinger software followed by molecular dynamics simulation study using Desmond module, and ADMET analysis. Interestingly, orlistat which is a well-known lipase and fatty acid synthase inhibitor also demonstrated favorable binding affinity with both PPAR-α/γ (-10.96 kcal/mol against PPARα and -10.26 kcal/mol against PPARγ). The highest docking scores were however shown by the flavonoids - rutin (-14.88 kcal/mol against PPARα and -13.64 kcal/mol against PPARγ), and its aglycone, quercetin (-10.08 kcal/mol in PPARα and -9.89 kcal/mol in PPARγ). The other phytochemicals (genistein, esculin, daidzin, naringenin, daidzein, dihydroxy coumarin, hydroquinone) showed lower binding affinity as dual agonists. The anti-obesity effects were experimentally validated in cultured adipocytes, which revealed better lipid inhibition by rutin and quercetin than orlistat (quercetin > rutin > orlistat) pointing to their strong potential in anti-obesity treatment.

Topics: Anti-Obesity Agents; Humans; Ligands; Lipids; Metabolic Syndrome; Molecular Docking Simulation; Non-alcoholic Fatty Liver Disease; Obesity; Orlistat; Phytochemicals; PPAR alpha; PPAR gamma; Quercetin; Rutin

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

The prevalence of obesity is surging in an alarming rate all over the world. Pharmaceutical drugs are considered potential adjunctive therapy to lifestyle modification. However, for most, besides being too expensive, their long term usages are hindered by their severe adverse effects. Here we describe the effect of UP601, a standardized blend of extracts from Morus alba, Yerba mate and Magnolia officinalis, in modulating a number of obesity-related phenotypic and biochemical markers in a high-fat high-fructose (HFF)-induced C57BL/6J mouse model of obesity.. Adipogenesis activity of the composition was assessed in 3T3-L1 cells in vitro. Effects of UP601 on body weight and metabolic markers were evaluated. It was administered at oral doses of 300 mg/kg, 450 mg/kg and 600 mg/kg for 7 weeks. Orlistat (40 mg/kg/day) was used as a positive control. Body compositions of mice were assessed using dual energy X-ray absorptiometry (DEXA). Serum biomarkers were measured for liver function and lipid profiling. Relative organ weights were determined. Histopathological analysis was performed for non-alcoholic steatohepatitis (NASH) scoring.. UP601 at 250 μg/ml resulted in 1.8-fold increase in lipolysis. Statistically significant changes in body weight (decreased by 9.1, 19.6 and 25.6% compared to the HFF group at week-7) were observed for mice treated with UP601 at 300, 450 and 600 mg/kg, respectively. Reductions of 9.1, 16.9, and 18.6% in total cholesterol; 45.0, 55.0, 63.6% in triglyceride; 34.8, 37.1 and 41.6% in LDL; 3.2, 21.6 (P = 0.03) and 33.7% (P = 0.005) in serum glucose were observed for UP601 at 300, 450 and 600 mg/kg, respectively. Body fat distribution was found reduced by 31.6 and 17.2% for the 450 mg/kg UP601 and orlistat, respectively, from the DEXA scan analysis. Up to an 89.1% reduction in mesenteric fat deposit was observed for UP601 in relative organ weight. Statistically significant improvements in NASH scores were observed for mice treated with UP601.. UP601, a standardized botanical composition from Morus alba, Yerba mate and Magnolia officinalis could potentially be used for achieving healthy weight loss and maintenance.

Topics: 3T3-L1 Cells; Adipogenesis; Animals; Blood Glucose; Body Fat Distribution; Diet; Disease Models, Animal; Hypoglycemic Agents; Hypolipidemic Agents; Ilex; Lactones; Lipids; Lipolysis; Liver; Magnolia; Mice; Mice, Inbred C57BL; Morus; Non-alcoholic Fatty Liver Disease; Obesity; Orlistat; Phytotherapy; Plant Extracts; Weight Loss