orlistat and Fatty-Liver

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

Overnutrition resulting in obesity plays a key role in nonalcoholic fatty liver disease, the major reason for abnormal liver function in many parts of the world. Currently, it is not clear which type of diet preferentially results in this common disease.. Excess nutrition leads to accumulation of various lipids in the liver, where fatty acids are considered the main driving force in the disease process. A liver loaded with fat is commonly associated with insulin resistance, the key pathophysiological phenomenon observed in nonalcoholic fatty liver disease. Not surprisingly, attempts to reduce body weight and thereby total liver fat are considered the key therapeutical steps in this disorder. Although voluntary weight loss is often not successful to reverse the disease process, various surgical procedures have proven effective in reducing overweight situations and liver steatosis. Weight loss not only reduces the amount of liver fat but also might improve inflammation and fibrosis in nonalcoholic steatohepatitis.. Although pharmacological approaches are eagerly awaited to achieve similar benefits; current available therapies have so far not fulfilled this expectation. Despite this frustration, such approaches are expected to be available in the near future.

Topics: Animals; Anti-Obesity Agents; Cytokines; Diet; Exercise Therapy; Fatty Liver; Humans; Lactones; Lipids; Obesity; Orlistat; Oxidative Stress; Weight Loss

Obesity prevalence is growing as well as its severity with increasing morbidity and mortality. This "globesity" also affects developing countries where under nutrition and stunting frequently coexist with overweight and obesity. One third of obese adults began to be so in the pediatric ages. There are two main types of prevention: general one representing greater actions from health authorities and the individual one carried out by the pediatrician and the patient at risk. Once the state of obesity is reached (relative body mass index, rBMI >121%) the longer lasting care becomes more complex and frequently unsuccessful. The treatment of obesity is aimed to care for the present and silent disorders and for preventing its further tracking to adulthood.. Identification of pediatric population at risk which is the one with an rBMI of 111%-120% plus other risk factors. Specific individual actions include reduction of food intake, increase of energy expenditure, involvement of parents, and the child-adolescent himself in the prevention. Therapy is based on some principles plus the important medical and emotional approach.. A Cochrane study based on only 10 appropriate studies showed a predominant poor efficacy of the undergone preventive action. Treatment guides are presented after our own experience with a group of 400 kids with an average follow-up of 7 years and other individual prevention studies.. Involving motivated pediatricians with a minimum of time for visits and better follow-up in the frame of a general national preventive programme could be a rational outcome. Treatment of obesity should never be postponed whatever the clinical care is.

Topics: Adolescent; Anti-Obesity Agents; Child; Child, Preschool; Comorbidity; Fatty Liver; Feeding Behavior; Female; Humans; Infant; Lactones; Male; Motor Activity; Obesity; Orlistat; Pediatrics; Physician's Role; Socioeconomic Factors

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

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

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that can progress to cirrhosis and hepatocellular carcinoma. NAFLD has been associated with obesity and other features of the metabolic syndrome, including insulin resistance, impaired glucose tolerance, and dyslipidemia. As a result, and with a lack of other effective treatments, weight loss achieved through lifestyle modifications (diet and exercise) has been promoted as the standard treatment. However, there is very little empiric evidence to support the effectiveness of weight loss for NAFLD. This article reviews the current literature on the effects of weight loss achieved through lifestyle modification or medications on NAFLD. To date, there have been no randomized controlled trials of weight loss interventions on hepatic pathology. Only three published trials (N = 89 subjects), which include a comparison group, have been published. These studies suggest improvement in liver enzymes and/or hepatic pathology; however, direct between group comparisons are lacking. Four small, nonrandomized studies (N = 59 subjects) have evaluated the effect of weight loss achieved with medications (4 of orlistat, 1 of sibutramine) on NAFLD. These suggest some improvement in liver enzymes and histopathology. Finally, a brief review of observational studies on the association between NAFLD pathology or liver enzymes and diet composition suggests a possible role for the manipulation of macronutrients and/or micronutrients in NAFLD treatment. In summary, there is little empiric evidence to support the role of weight loss achieved through lifestyle modification or medication in the treatment of NAFLD. Rigorously conducted, randomized controlled trials are needed in this area.

Topics: Anti-Obesity Agents; Appetite Depressants; Bariatric Surgery; Chronic Disease; Cyclobutanes; Diet, Reducing; Disease Progression; Fatty Liver; Humans; Lactones; Life Style; Orlistat; Weight Loss

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

Non-alcoholic fatty liver disease is now recognized as a cause of potentially progressive liver damage, posing patients at risk of advanced liver failure. Unfortunately, the natural history of disease is only partly known, the disease is slowly progressive and therapeutic outcomes are difficult to define. These factors have limited therapeutic trials to pilot studies, and very few randomized-controlled studies are available. The concept that insulin-resistance, coupled with oxidative stress, may be the underlying mechanism responsible for fat accumulation and disease progression points to insulin-sensitizing agents (metformin, thiazolidinediones) as the most promising drugs. They proved effective in reducing enzyme levels in the short period, but very limited information is available on liver histology, not to say progression to liver cell failure. Large, long-term, placebo-controlled randomized studies are eagerly awaited. Outside controlled studies, nutritional counselling and physical exercise aimed at moderate weight loss remain the basis of any therapeutic intervention.

Topics: Antioxidants; Cholagogues and Choleretics; Cytoprotection; Enzyme Inhibitors; Fatty Liver; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Lactones; Life Style; Lipase; Metformin; Orlistat; Phlebotomy; Thiazolidinediones; Ursodeoxycholic Acid

Losing weight by lifestyle interventions is the first-line treatment for metabolic-associated fatty liver disease (MAFLD) but is limited by low compliance.. This study aimed to compare the effects of orlistat or an experimental high-protein/lower-carbohydrate diet with a control diet in Asian patients with obesity and MAFLD.. A total of 118 Asian patients with obesity and MAFLD confirmed with MRI-based proton density fat fraction with Dixon sequence were enrolled and allocated to the control group, the orlistat group, or the experimental diet group for 24 wk. The primary endpoint was the relative change in liver fat content (LFC) assessed by MRI-based proton density fat fraction.. A total of 118 subjects with obesity and MAFLD were randomly assigned to the control group (n = 39), the orlistat group (n = 40), or the experimental diet group (n = 39). All 3 groups demonstrated improvement in liver steatosis at wk 24. The absolute decrease in LFC in the orlistat group was 9.1% and 5.4% in the experimental diet group, both significantly higher than that in the control group (P < 0.05). The relative reduction in LFC was 30.2% in the experimental diet group, which was significantly higher than the 12.2% observed in the control group (P = 0.01).. Orlistat and the experimental diet group reduced liver steatosis compared to the control group. This trial was registered at Chinese Clinical Trial Registry (ChiCTR-1900027172). http://www.chictr.org.cn.

Topics: Anti-Obesity Agents; Diet; Fatty Liver; Humans; Lactones; Liver Diseases; Obesity; Orlistat; Protons

The aim of this study was to determine if orlistat, an inhibitor of fat absorption, combined with caloric restriction in overweight subjects with nonalcoholic steatohepatitis results in weight loss and improved liver histology. Fifty overweight subjects (body mass index = >or=27) with biopsy proven nonalcoholic steatohepatitis were randomized to receive a 1,400 Kcal/day diet plus vitamin E (800 IU) daily with or without orlistat (120 mg three times a day) for 36 weeks. Liver biopsies were repeated at week 36. Twenty-three subjects in the orlistat/diet/vitamin E group and 18 in the diet/vitamin E group completed the study. The mean age was 47 +/- 9.0 (standard deviation) years and mean body mass index was 36.4 +/- 6.3 kg/m(2). Four subjects were diabetic. The orlistat group lost a mean of 8.3% body weight compared to 6.0% in the diet plus vitamin E group (not significant). Both groups also had similarly improved serum aminotransferases, hepatic steatosis, necroinflammation, ballooning, and nonalcoholic fatty liver disease activity scores. Stratified according to weight loss instead of treatment group, a loss of >or=5% body weight (n = 24) compared to <5% body weight (n = 17) correlated with improvement in insulin sensitivity (P = 0.001) and steatosis (P = 0.015). Comparing subjects who lost >or=9% of body weight (n = 16), to those that did not (n = 25), improved insulin sensitivity (P < 0.001), adiponectin (P = 0.03), steatosis (P = 0.005), ballooning (P = 0.04), inflammation (P = 0.045), and nonalcoholic fatty liver disease activity score (P = 0.009) were seen. Increases in adiponectin strongly correlated with improved ballooning and nonalcoholic fatty liver disease activity score (P = 0.03). Orlistat did not enhance weight loss or improve liver enzymes, measures of insulin resistance, and histopathology. However, subjects who lost >or=5% of body weight over 9 months improved insulin resistance and steatosis, and those subjects who lost >or=9% also achieved improved hepatic histologic changes.

Topics: Adult; Anti-Obesity Agents; Diet, Reducing; Fatty Liver; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Weight Loss

Topics: Adult; Anti-Obesity Agents; Fatty Liver; Female; Humans; Lactones; Liver Cirrhosis; Male; Middle Aged; Obesity; Orlistat; Treatment Outcome; Weight Loss

Few controlled studies have addressed the issue of effective medical treatment for nonalcoholic fatty liver disease (NAFLD). We herein assessed the effect of orlistat in patients with NAFLD.. We performed a randomized, double-blind, placebo-controlled study on 52 patients with NAFLD diagnosed by ultrasound (US) and confirmed by liver biopsy (40 patients). The patients were randomized to receive either orlistat (120 mg 3 times daily for 6 months) or placebo. All patients participated in an identical behavioral weight loss program. All patients underwent monthly evaluation by abdominal US; liver enzyme levels, lipid profiles, insulin levels, and anthropometric parameters were monitored, and all patients underwent nutritional follow-up evaluation. Twenty-two patients underwent a second liver biopsy examination at the end of the study.. Fifty-two patients were recruited and 44 (mean age, 47.7 y; mean body mass index, 33) completed the study. Serum glucose and insulin levels (P<.03) were significantly higher in the orlistat group, which also presented a higher degree of fibrosis. Body mass index was reduced significantly in each group, with a nonsignificant difference between the groups. Serum alanine transaminase (ALT) levels decreased significantly in both groups, with an almost 2-fold reduction in the orlistat group (48% vs 26.4%). There was a statistically significant reversal of fatty liver by US only in the orlistat group (P<.05).. Orlistat improves serum ALT levels and steatosis on US in NAFLD patients, beyond its effect on weight reduction.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Biopsy, Needle; Body Mass Index; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Fatty Liver; Female; Follow-Up Studies; Humans; Immunohistochemistry; Lactones; Liver Function Tests; Male; Middle Aged; Orlistat; Probability; Reference Values; Risk Assessment; Severity of Illness Index; Treatment Outcome; Ultrasonography, Doppler; Weight Loss

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS). There is no established treatment for NAFLD.. To evaluate a multifactorial intervention in the treatment of NAFLD.. A prospective, open-label, randomised study in non-diabetic patients (n = 186) with MetS (follow-up: 54 weeks). All patients had both biochemical and ultrasonographic evidence of NAFLD at baseline. Other causes of liver disease were excluded. Patients received lifestyle advice and treatment for hypertension (mainly inhibitors of the renin-angiotensin system), impaired fasting glucose (metformin), obesity (orlistat) and dyslipidaemia [randomly allocated to atorvastatin 20 mg/day (n = 63) or micronised fenofibrate 200 mg/day (n = 62) or both drugs (n = 61)]. Liver ultrasonography was assessed at baseline and at the end of the study.. At the end of treatment, 67% of patients on atorvastatin, 42% on fenofibrate and 70% on combination treatment no longer had biochemical plus ultrasonographic evidence of NAFLD (p < 0.05 vs. baseline for all comparisons). The percentage of patients who no longer had evidence of NAFLD was significantly higher (p < 0.009) in the atorvastatin and combination groups compared with the fenofibrate group. This effect was independently related to drug treatment, as well as to reductions in high-sensitivity C-reactive protein, waist circumference, body weight, triglycerides, low-density lipoprotein-cholesterol, total cholesterol, systolic blood pressure and glucose. Four patients discontinued treatment because of adverse effects.. Multifactorial intervention in MetS patients with both biochemical and ultrasonographic evidence of NAFLD offsets surrogate markers of NAFLD (i.e. elevated aminotransferase plus echogenic liver).

Topics: Anti-Obesity Agents; Atorvastatin; Diet, Fat-Restricted; Drug Therapy, Combination; Dyslipidemias; Fatty Liver; Female; Fenofibrate; Heptanoic Acids; Humans; Hypolipidemic Agents; Lactones; Male; Metabolic Syndrome; Middle Aged; Orlistat; Prevalence; Prospective Studies; Pyrroles; Risk Factors; Treatment Outcome; Ultrasonography; Weight Loss

Treatment options for non-alcoholic steatohepatitis (NASH) are limited. Weight loss remains the most recommended therapy. Orlistat is an effective adjunct to dietary weight loss therapy.. To evaluate the efficacy of orlistat, given for 6 months to patients with obesity and biopsy confirmed NASH.. Ten obese patients with biopsy proven NASH were enrolled. Orlistat was given with meals for 6 months. Body Mass Index (BMI), liver enzymes, haemoglobin A1c, fasting lipids and glucose were assessed at baseline and at completion of the study. Paired liver histology was obtained.. Six women and four men were enrolled. The mean weight loss was 22.7 lb and ranged from 0 to 24.3%. The following clinical values significantly improved: mean BMI: 43.4-39.8 (P = 0.007); mean haemoglobin A1c (%): 7.14-5.95 (P = 0.021); mean alanine aminotransferase (ALT) (U/L): 93 -54 (P = 0.009); and mean aspartate aminotransferase (AST) (U/L): 79-48 (P = 0.008). Steatosis improved in six patients, and fibrosis improved in three patients.. Orlistat therapy and dietary counselling were associated with significant decreases in body weight, haemoglobin A1c, ALT and AST. A 10% or greater reduction in weight improved steatosis and fibrosis as well as haemoglobin A1c levels in the majority of patients treated for 6 months. Controlled trials of longer duration are warranted to assess for histopathologic improvement as well as cost-efficacy in comparison to diet and exercise alone.

Topics: Aged; Anti-Obesity Agents; Fatty Liver; Female; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Weight Loss

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

Obesity is a multi-factorial metabolic syndrome that increases the risk of cardiovascular diseases, diabetes, and cancer. We recently demonstrated the antiadipogenic efficacy of lutein using a 3 T3-L1 cell culture model. This study aimed to examine the antiobesity efficacy of lutein on high-fat (60% kcal fat) diet-induced C57BL/6J obese mice model. Lutein (300 and 500 μM), Orlistat (30 mg/kg body weight - positive control), and its combination (orlistat, 15 mg/kg body weight+lutein, 300 μM) were administered in high-fat diet (HFD)-fed mice every other day for 24 weeks. The effect on serum and hepatic lipid parameters was estimated using biochemical assay kits. The adipose tissue expression of adipocyte differentiation markers at gene and protein levels was analyzed by RT-PCR and western blotting, respectively. The results showed that lutein administration and drug significantly reduced epididymal and abdominal adipose tissue weights. Further, lutein reduced the serum cholesterol and LDL-C concentration compared to the HFD group. The HFD-induced elevation in the hepatic triglycerides and cholesterol levels were significantly blocked by lutein and its combination with the drug. Similarly, lutein and its drug combination efficiently lowered the HFD-mediated elevated blood glucose levels. Lutein downregulated the expression of CEBP-α, PPAR-γ, and FAS in the epididymal adipose tissue. Thus, supplementation of lutein may control diet-induced obesity and associated complications in the human population.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Cholesterol; Diet, High-Fat; Fatty Liver; Glucose Intolerance; Humans; Liver; Lutein; Mice; Mice, Inbred C57BL; Obesity; Orlistat

Orlistat is an intestinal lipase inhibitor drug that is recommended in obese patients along with a hypocaloric diet. Although the most frequent secondary effect is steatorrhea, fulminant liver failure has also been associated with this drug, which has required liver transplantation in 3 patients. We present the case of a 42-year-old obese male.

Topics: Adult; Anti-Obesity Agents; Fatty Liver; Humans; Liver Failure, Acute; Male; Massive Hepatic Necrosis; Obesity; Orlistat

Topics: Anti-Obesity Agents; Fatty Liver; Humans; Lactones; Orlistat; Overweight

Topics: Anti-Obesity Agents; Fatty Liver; Humans; Lactones; Orlistat; Overweight

Specific therapy for non-alcoholic steatohepatitis (NASH) is needed because of the potential severity of this liver disease. NASH is a recognized cause of cryptogenic cirrhosis and, increasingly, of hepatocellular carcinoma. Therefore, there is an unmet medical need for the therapy of NASH. This article discusses this therapy, with particular emphasis on pharmacologic therapy.

Topics: Angiotensin II Type 1 Receptor Blockers; Anti-Obesity Agents; Antioxidants; Betaine; Cholagogues and Choleretics; Clinical Trials as Topic; Fatty Liver; Free Radical Scavengers; Humans; Lactones; Lipotropic Agents; Orlistat; Pentoxifylline; Probucol; Thiazolidinediones; Tocopherols; Ursodeoxycholic Acid

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

Topics: Adult; Biopsy; Body Mass Index; Enzyme Inhibitors; Fatty Liver; Female; Follow-Up Studies; Humans; Lactones; Lipase; Liver Cirrhosis; Male; Middle Aged; Obesity; Orlistat; Recovery of Function; Severity of Illness Index; Transaminases; Treatment Outcome

Nonalcoholic steatohepatitis is now recognized as a common chronic liver disorder. Up to 16% of affected patients may progress to cirrhosis. The incidence and prevalence of this disease are noted to be increasing, in parallel with the nationwide increase in obesity and diabetes. Treatment options for these patients remain quite limited, however. Weight reduction has been advocated, but there are little data to support this practice, as most patients are unable to comply with the proper dietary modifications. We report three obese patients with biopsy-proven nonalcoholic steatohepatitis treated for 6-12 months with a weight reduction medication, orlistat, who lost between 22-42 lb, and had significant clinical and histopathological improvement on follow-up.

Topics: Adult; Anti-Obesity Agents; Fatty Liver; Female; Hepatitis; Humans; Lactones; Middle Aged; Obesity; Orlistat