Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this review, we would like to consider several aspects of the discovery of leptin and its evolution as a therapeutic agent. It has been shown that the administration of leptin in congenital leptin deficiency that there was improvement in satiety and weight loss. In hypoleptinemic patients with lipodystrophy, there is a dramatic improvement in glucose metabolism, dyslipidemia and hepatic steatosis. Leptin is the first and only adipokine administered to humans long term to produce such an effect.
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PMID:The clinical efficacy of the adipocyte-derived hormone leptin in metabolic dysfunction. 1693 53

Hepatic steatosis is an emerging cause of morbidity in antiretroviral therapy (ART)-experienced HIV patients. The influence of steatosis on fibrosis is poorly understood. We report two cases of rapid evolution of disseminated macrovacuolar steatofibrosis to cirrhosis. Both patients had no history of alcohol abuse, nor intravenous drug use and were tested negative for HCV (PCR RNA) and had no HBS antigen. Patient 1 had a past history of hypertrygliceridemia, but controlled with dietetic measures for 4 years prior to biopsy. The first hepatic biopsy showed a disseminated macrovacuolar steatosis (>80%). The patient had then cytolysis and an uncontrolled HIV viral load. The second biopsy was performed two years later, and HIV was controlled by a new line of ART. It showed a regression of the steatosis (10%) and a progression of the fibrosis with signs of cirrhosis. Patient 2 had a long history of HIV infection. He also had an uncontrolled dyslipidemia. The first biopsy was realised during a period of uncontrolled HIV infection and elevated liver enzymes. The biopsy showed a major macrovacuolar steatosis (>80%). The second biopsy was realised 6 years after and showed the same steatosis and signs of cirrhosis. The HIV infection was then under control. Observations reported here show a rapid evolution of liver steatosis to cirrhosis in HIV positive / HCV negative patients, despite the control of HIV infection. The implication of HAART remains unclear. In the era of HAART, liver steatosis can rapidly evoluate to cirrhosis without any risk factor except ART.
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PMID:[Hepatic steatosis: an emerging cause of cirrhosis in HIV patients]. 1702 88

With the increasing number of bariatric surgical procedures being performed, outcome assessment is of even greater importance. Few randomized, controlled prospective trials have compared bariatric surgery to nonsurgical weight-loss treatments, and the quality of current outcome data is suboptimal. However, the available evidence suggests that bariatric surgery, and particularly gastric bypass, is the most effective weight-loss treatment for people with extreme (class III) obesity. In addition to reduced energy intake and to a lesser extent malabsorption, numerous other potential mechanisms related to bariatric surgery may play a role in promoting weight loss and improving comorbidities. After bariatric surgery, clinical improvement or resolution has been reported in 64% to 100% of patients with diabetes mellitus, 62% to 69% of patients with hypertension, 85% of patients with obstructive sleep apnea, 60% to 100% of patients with dyslipidemia, and up to 90% of patients with nonalcoholic fatty liver disease. A wide range of other weight-related conditions also appear to improve, and limited data suggest that overall mortality may decrease in patients undergoing bariatric surgery. Although not conclusive, evidence from available studies indicates that bariatric surgery is cost-effective. Further research with improved methodology is needed to define the mechanisms of action of bariatric surgery; to document its effect on long-term weight loss, comorbid conditions, and overall mortality; and to determine its cost-effectiveness.
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PMID:Long-term outcome of bariatric surgery: an interim analysis. 1703 78

Bile acid-binding resins, such as cholestyramine and colestimide, have been clinically used as cholesterol-lowering agents. These agents bind bile acids in the intestine and reduce enterohepatic circulation of bile acids, leading to accelerated conversion of cholesterol to bile acids. A significant improvement in glycemic control was reported in patients with type 2 diabetes whose hyperlipidemia was treated with bile acid-binding resins. To confirm the effect of such drugs on glucose metabolism and to investigate the underlying mechanisms, an animal model of type 2 diabetes was given a high-fat diet with and without colestimide. Diet-induced obesity and fatty liver were markedly ameliorated by colestimide without decreasing the food intake. Hyperglycemia, insulin resistance, and insulin response to glucose, as well as dyslipidemia, were markedly and significantly ameliorated by the treatment. Gene expression of the liver indicated reduced expression of small heterodimer partner, a pleiotropic regulator of diverse metabolic pathways, as well as genes for both fatty acid synthesis and gluconeogenesis, by treatment with colestimide. This study provides a molecular basis for a link between bile acids and glucose metabolism and suggests the bile acid metabolism pathway as a novel therapeutic target for the treatment of obesity, insulin resistance, and type 2 diabetes.
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PMID:Prevention and treatment of obesity, insulin resistance, and diabetes by bile acid-binding resin. 1719 88

High sucrose (HS) feeding in rats induces hepatic steatosis and plasma dyslipidemia. In previous reports (Huang W, Dedousis N, Bhatt BA, O'Doherty RM. J Biol Chem 279: 21695-21700, 2004; and Huang W, Dedousis N, Bandi A, Lopaschuk GD, O'Doherty RM. Endocrinology 147: 1480-1487, 2006), our laboratory demonstrated a rapid ( approximately 100 min) leptin-induced decrease in liver and plasma VLDL triglycerides (TG) in lean rats, effects that were abolished in obese rats fed a high-fat diet, a model that also presents with hepatic steatosis and plasma dyslipidemia. To further examine the capacity of acute leptin treatment to improve metabolic abnormalities induced by nutrient excess, hepatic leptin action was studied in rats after 5 wk of HS feeding. HS feeding induced hepatic steatosis (TG+80+/-8%; P=0.001), plasma hyperlipidemia (VLDL-TG+102+/-14%; P=0.001), hyperinsulinemia (plasma insulin +67+/-12%; P=0.04), and insulin resistance as measured by homeostasis model assessment (+125+/-20%; P=0.02), without increases in adiposity or plasma leptin concentration compared with standard chow-fed controls. A 120-min infusion of leptin (plasma leptin 13.6+/-0.7 ng/ml) corrected hepatic steatosis (liver TG-29+/-3%; P=0.003) and plasma hyperlipidemia in HS (VLDL-TG-42+/-4%; P=0.001) and increased plasma ketones (+45+/-3%; P=0.006), without altering plasma glucose, insulin, or homeostasis model assessment compared with saline-infused HS controls. In addition, leptin activated liver phosphatidylinositol 3-kinase (+70+/-18%; P=0.01) and protein kinase B (Akt; +90+/-29%; P=0.02), and inhibited acetyl-CoA carboxylase (40+/-7%; P=0.04) in HS, further demonstrating that hepatic leptin action was intact in these animals. We conclude that 1) leptin action on hepatic lipid metabolism remains intact in HS-fed rats, 2) leptin rapidly reverses hepatic steatosis and plasma dyslipidemia induced by sucrose, and 3) the preservation of hepatic leptin action after a HS diet is associated with the maintenance of low adiposity and plasma leptin concentrations.
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PMID:Hepatic steatosis and plasma dyslipidemia induced by a high-sucrose diet are corrected by an acute leptin infusion. 1736 21

Metabolic and inflammatory pathways crosstalk at many levels, and, while required for homeostasis, interaction between these pathways can also lead to metabolic dysregulation under conditions of chronic stress. Thus, we hypothesized that mechanisms might exist to prevent overt inflammatory responses during physiological fluctuations in nutrients or under nutrient-rich conditions, and we identified the six-transmembrane protein STAMP2 as a critical modulator of this integrated response system of inflammation and metabolism in adipocytes. Lack of STAMP2 in adipocytes results in aberrant inflammatory responses to both nutrients and acute inflammatory stimuli. Similarly, in whole animals, visceral adipose tissue of STAMP2(-/-) mice exhibits overt inflammation, and these mice develop spontaneous metabolic disease on a regular diet, manifesting insulin resistance, glucose intolerance, mild hyperglycemia, dyslipidemia, and fatty liver disease. We conclude that STAMP2 participates in integrating inflammatory and metabolic responses and thus plays a key role in systemic metabolic homeostasis.
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PMID:Coordinated regulation of nutrient and inflammatory responses by STAMP2 is essential for metabolic homeostasis. 1748 36

Elevations in alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), markers of liver dysfunction and nonalcoholic fatty liver, are considered as part of the metabolic syndrome and related diseases. However, information is limited regarding the persistence (tracking) in levels of these enzymes over time and their influence on cardiovascular (CV) risk in young adults. The study sample consisted of white and black subjects (N = 489, 40% male, 73% white; baseline age, 18-32 years) followed over a period of 12 years as part of the Bogalusa Heart Study, with repeat measurements of CV risk factor variables and liver enzymes. Both at baseline and follow-up, males vs females had higher ALT (P < .01 to .0001) and GGT (P < .0001); blacks vs whites had higher GGT (P < .0001). With respect to persistence in enzyme levels over time, of those individuals who had ALT and GGT at the top quintile specific for age, race, and sex at baseline, about 50% of them continued to remain so with high values after 12 years. Individuals with levels persistently in the highest quintile vs those in the lowest quintile showed higher (P < .0001) body mass index, waist circumference, triglycerides, low-density lipoprotein cholesterol, glucose, insulin, insulin resistance index, and systolic and diastolic blood pressures; lower (P < .0001) high-density lipoprotein cholesterol; and higher (P < .05 to .001) prevalence of obesity, hypertension, dyslipidemia, metabolic syndrome as defined by the National Cholesterol Education Program Adult Treatment Panel III, positive parental history of type 2 diabetes, and coronary heart disease. In addition, based on a multivariate analysis using 2 separate models for ALT and GGT, baseline levels of both enzymes were independent predictors of follow-up; insulin resistance index and baseline GGT were also predictive of follow-up systolic blood pressure. Elevations in liver enzymes ALT and GGT, within "reference" range, persist over time and relate to clinically relevant adverse CV risk profile in young adults.
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PMID:Persistent elevation of liver function enzymes within the reference range is associated with increased cardiovascular risk in young adults: the Bogalusa Heart Study. 1751 12

This study investigated the effects of rimonabant (SR141716), an antagonist of the cannabinoid receptor type 1 (CB1), on obesity-associated hepatic steatosis and related features of metabolic syndrome: inflammation (elevated plasma levels of tumor necrosis factor alpha [TNFalpha]), dyslipidemia, and reduced plasma levels of adiponectin. We report that oral treatment of obese (fa/fa) rats with rimonabant (30 mg/kg) daily for 8 weeks abolished hepatic steatosis. This treatment reduced hepatomegaly, reduced elevation of plasma levels of enzyme markers of hepatic damage (alanine aminotransferase, gamma glutamyltransferase, and alkaline phosphatase) and decreased the high level of local hepatic TNFalpha currently associated with steatohepatitis. In parallel, treatment of obese (fa/fa) rats with rimonabant reduced the high plasma level of the proinflammatory cytokine TNFalpha and increased the reduced plasma level of the anti-inflammatory hormone adiponectin. Finally, rimonabant treatment also improved dyslipidemia by both decreasing plasma levels of triglycerides, free fatty acids, and total cholesterol and increasing the HDLc/LDLc ratio. All the effects of rimonabant found in this study were not or only slightly observed in pair-fed obese animals, highlighting the additional beneficial effects of treatment with rimonabant compared to diet. These results demonstrate that rimonabant plays a hepatoprotective role and suggest that this CB1 receptor antagonist potentially has clinical applications in the treatment of obesity-associated liver diseases and related features of metabolic syndrome.
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PMID:Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic syndrome in obese Zucker fa/fa rats. 1759 67

Risk factors for development of non-alcoholic steatohepatitis include obesity, especially central adiposity, glucose intolerance or type 2 diabetes mellitus (T2DM), and dyslipidemia. Non-alcoholic fatty liver disease (NAFLD) is now considered a manifestation of metabolic syndrome. During the last two decades, NAFLD has become the most common chronic liver disease in North America and Europe, but until recently was thought to be uncommon (perhaps due to the lack of study) in Asia. Fatty liver can be identified on imaging modalities (ultrasonography, computed tomography scans, and magnetic resonance imaging) with high sensitivity, but steatohepatitis and fibrosis cannot be distinguished. Thus, an inherent drawback in studying the epidemiology of NAFLD is the lack of definitive laboratory tests, no uniform definition-with different studies using cut-off values of alcohol consumption from <20 g/week to 210 g/week, and case selections where biopsy was used for definition. In studies outside the region, the prevalence of NAFLD varies from 16% to 42% by imaging, and 15-39% of liver biopsies. The major risk factors for NAFLD, central obesity, T2DM, dyslipidemia, and metabolic syndrome, are now widely prevalent and are increasing geometrically in the Asia-Pacific region. It is therefore not surprising that NAFLD is common in this region. Estimates of current prevalence range from 5% to 30%, depending on the population studied. Central obesity, diabetes, and metabolic syndrome are the major risk factors. To date, however, data on the natural history and impact of NAFLD causing serious significant chronic liver disease are lacking and there is a need for prospective, cooperative studies.
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PMID:How common is non-alcoholic fatty liver disease in the Asia-Pacific region and are there local differences? 1756 29

Polycystic ovary syndrome (PCOS) affects 6-7% of reproductive-aged women. Although the diagnostic criteria for PCOS have been debated, it is frequently characterized by hyperandrogenism (hirsutism, acne, male-pattern hair loss), oligo-anovulation, and polycystic ovaries on ultrasound. The reproductive and metabolic complications associated with the syndrome can be serious, so a comprehensive approach to the evaluation and treatment of affected women is important. Menstrual cycle control is necessary to prevent endometrial hyperplasia, and this can be accomplished with hormonal contraception, progesterone therapy, and weight loss (if overweight). In women desiring pregnancy, commonly used ovulation induction therapies include weight loss, clomiphene citrate, and/or metformin. Cosmetic issues such as hirsutism, acne and male-pattern hair loss can be challenging to cope with. Treatment options include estrogen-containing hormonal contraceptive agents, antiandrogens, and topical agents. More permanent hair reduction can be achieved with electrolysis and laser therapy. Evaluation of metabolic complications includes risk assessment for diabetes, dyslipidemia, hypertension, and nonalcoholic fatty liver disease. Women with PCOS should also be screened for sleep apnea, as this has been reported to occur more commonly in women with PCOS. Finally, mental health issues such as depression and eating disorders may be present. Many of the complications associated with PCOS can be managed with therapeutic lifestyle change, including a healthy diet, exercise, weight loss (if overweight), and psychological support. Pharmacological therapies are also available to effectively regulate menstrual cycles and manage cosmetic complications. This article will review the current diagnostic and therapeutic strategies in PCOS.
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PMID:Comprehensive clinical management of polycystic ovary syndrome. 1759 39


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