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)

A retrospective study was performed to (1) characterize the clinical and histologic features of those with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) values, (2) compare the spectrum of NAFLD associated with normal versus elevated ALT levels, and (3) determine whether there were differences in the clinical or histologic spectrum of NAFLD between those with a low normal versus high normal ALT value. A total of 51 subjects with NAFLD and normal ALT were identified and compared with 50 consecutive subjects with NAFLD and elevated ALT. The major indications for liver biopsy in those with normal ALT were unexplained hepatomegaly (n = 21) and evaluation as a potential donor for living donor liver transplantation (n = 16). The 2 groups were comparable with respect to age, gender distribution, and ethnicity. Approximately 80% of cases in both groups had at least 1 feature of the metabolic syndrome, the major risk factor for NAFLD. The 2 groups were also comparable with respect to the grade of the individual histologic parameters of NAFLD. A total of 12 subjects with normal ALT levels had bridging fibrosis, whereas 6 had cirrhosis. Diabetes was the only factor independently associated with an increased risk of advanced fibrosis (bridging fibrosis or cirrhosis) by multivariate analysis (relative risk: 2.3, P <.01). The mean steatosis (1.6 vs. 2.16, P <.04) and perisinusoidal fibrosis scores (0.35 vs. 0.9, P <.049) were lower in those with low normal (<30 IU/L) ALT versus high normal ALT. However, the prevalence of advanced fibrosis was similar (5 of 15 vs. 13 of 36, respectively). In conclusion, (1) the entire histologic spectrum of NAFLD can be seen in individuals with normal ALT values, (2) the histologic spectrum in these individuals is not significantly different from those with elevated ALT levels, and (3) a low normal ALT value does not guarantee freedom from underlying steatohepatitis with advanced fibrosis.
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PMID:Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. 1505 21

Chronic liver disease is a major cause of morbidity and mortality in the United States. Although often used to detect liver disease, the prevalence and etiology of elevated aminotransferases are unknown. We analyzed data on adults ages 17 yr and older (N = 15,676) from the Third National Health and Nutrition Examination Survey (1988-1994). Participants were classified as having elevated aminotransferase levels if either aspartate aminotransferase or alanine aminotransferase was elevated above normal. Aminotransferase elevation was classified as "explained" if there was laboratory evidence of hepatitis B or C infection, iron overload, or if there was a history of alcohol consumption. Analyses were weighted to provide national estimates. The prevalence of aminotransferase elevation in the United States was 7.9%. Aminotransferase elevation was more common in men compared to women (9.3% vs 6.6%, p = 0.002), in Mexican Americans (14.9%) and non-Hispanic blacks (8.1%) compared to non-Hispanic whites (7.1%, p < 0.001). High alcohol consumption, hepatitis B or C infection and high transferrin saturation were found in only 31.0% of cases. Aminotransferase elevation was unexplained in the majority (69.0%). In both men and women, unexplained aminotransferase elevation was significantly associated with higher body mass index, waist circumference, triglycerides, fasting insulin, and lower HDL; and with type 2 diabetes and hypertension in women (all p < 0.05). Aminotransferase elevation was common in the United States, and the majority could not be unexplained by alcohol consumption, viral hepatitis or hemochromatosis. Unexplained aminotransferase elevation was strongly associated with adiposity and other features of the metabolic syndrome, and thus may represent nonalcoholic fatty liver disease.
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PMID:The prevalence and etiology of elevated aminotransferase levels in the United States. 1280 14

Nonalcoholic steatohepatitis (NASH), along with other forms of nonalcoholic fatty liver disease, is an increasingly common clinico-pathological syndrome. It is frequently associated with obesity, especially visceral fat, and type 2 diabetes, and is intimately related to markers of the insulin resistance syndrome. Both the prevalence and the severity of liver steatosis are related to body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridemia and impaired glucose tolerance. The pathophysiology of NASH involves two steps: 1) insulin resistance, which causes steatosis; 2) and oxidative stress, which produces lipid peroxidation and activates inflammatory cytokines. The identification of subjects who may progress from fatty liver to NASH, and from NASH to fibrosis/cirrhosis is an important clinical challenge as well as the finding of appropriate therapy that could prevent such deleterious process. Substantial weight loss is accompanied by a marked attenuation of insulin resistance and related metabolic syndrome and, concomitantly, by an important regression of liver steatosis in most patients, although mild inflammation may be detected in some subjects. Thus, NASH may be considered as another disease of affluence, as is the insulin resistance syndrome and perhaps being part of it.
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PMID:Nonalcoholic steatohepatitis and insulin resistance: interface between gastroenterologists and endocrinologists. 1283 90

Recent studies indicate that some patients with nonalcoholic fatty liver have ongoing liver injury that may progress from steatosis to steatohepatitis or fibrosis. The present study was designed to clarify the clinical features of liver dysfunction observed in the course of workplace physical check-ups in relation to multiple risk factor syndrome including obesity, hyperlipidemia, hypertension, and impaired glucose tolerance, and to clarify the involvement of aldehyde dehydrogenase 2 (ALDH2) and beta(3)-adrenergic receptor (beta3-AR) gene polymorphisms in elevation of liver enzymes. One hundred forty-eight male workers 35 years of age were enrolled. They were requested to answer questionnaires about drinking and smoking habits, and underwent urinalysis, physical and peripheral blood examinations, blood chemistry, electrocardiogram and chest x-rays. The genotypes of ALDH2 and beta3-AR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subjects were divided into active ALDH2 or inactive ALDH2 groups. They were also divided into 2 groups according to the beta3-AR genotype. The relationships between ALDH2 and beta3-AR gene polymorphism and the results of the physical examination including liver function tests were analyzed. The subjects were also divided according to the number of components of metabolic syndrome. The prevalence of elevated alanine aminotransferase (ALT) level increased with the accumulation of components of metabolic syndrome. Active ALDH2 was associated with elevated ALT level to a greater degree than beta3-AR polymorphism. Among those with normal body mass index (BMI), the genotypes of ALDH2 and beta3-AR were strongly associated with elevated ALT level. Logistic regression analysis revealed that BMI, triglyceride level, and ALDH2 genotype were associated with ALT elevation. In conclusion, evaluating the genotype of ALDH2 and beta3-AR may assist in predicting and preventing the development of fatty liver which may be related to multiple risk factor syndrome.
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PMID:Aldehyde dehydrogenase 2 and beta3-adrenergic receptor gene polymorphisms: their association with elevated liver enzymes and metabolic syndrome. 1450 13

The role of insulin resistance in non-alcoholic fatty liver disease is suggested by laboratory data (hyperinsulinemia and decreased sensitivity to endogenous and exogenous insulin). The clinical association with features of the metabolic syndrome, particularly in the most aggressive stages of the disease, further confirms a causative role. Fat accumulation in the liver may stem either from genetic defects, primarily responsible for insulin resistance, or excessive calorie intake and visceral obesity, and is mediated by adipocytokines (leptin, adiponectin, tumour necrosis factor-alpha). Progression of fatty liver to steatohepatitis may be the result of an imbalance between pro-inflammatory and anti-inflammatory cytokines, triggering the formation of reactive oxygen species and intrahepatic lipid peroxidation. This process may also be promoted or accelerated by pro-oxidant xenobiotics or environmental factors. Insulin resistance provides a target for specific treatment of non-alcoholic fatty liver, and insulin-sensitising agents (metformin or thiazolidinediones) as well as lifestyle changes to reduce visceral adiposity are the most promising therapeutic options. Future trials need to be performed in order to test the long-term effectiveness of these treatments on the basis of clinically relevant histological outcomes.
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PMID:Non-alcoholic fatty liver and insulin resistance: a cause-effect relationship? 1504 83

Patients with hypopituitarism develop a phenotype similar to metabolic syndrome with central obesity and diabetes. Similarly, patients with hypothalamic damage may develop central obesity, insulin resistance, and hyperphagia. We sought to examine the clinical associations between hypopituitarism, hypothalamic dysfunction, and nonalcoholic fatty liver disease (NAFLD). A case series of patients seen at our institution with diagnoses of hypopituitarism, hypothalamic obesity, or craniopharyngioma and NAFLD was undertaken. Clinical, laboratory, and liver biopsy features were reviewed. Twenty-one patients were identified. NAFLD was diagnosed 6.4 +/- 7.5 years (median 3 years) after the diagnosis of hypothalamic/pituitary dysfunction. Mean gain in body mass index (BMI) between diagnoses of hypothalamic/pituitary disease and NAFLD was 11.3 +/- 8.9 kg/m(2) at an average yearly rate of 2.2 +/- 2.2 kg/m(2). The majority of patients developed elevated glucose levels and dyslipidemia by time of diagnosis of NAFLD. Of the 10 patients biopsied, six were cirrhotic, two had nonalcoholic steatohepatitis (NASH) with fibrosis, and two had simple steatosis. Long-term follow-up of 66 +/- 33 months (range 12-120) was available for 18 patients. Two required liver transplantation. Six patients died, two from liver related causes. In conclusion, patients with hypothalamic and/or pituitary disease are at risk of excessive weight gain, impaired glucose tolerance, and dyslipidemia with subsequent development of NAFLD. This group has a high prevalence of cirrhosis placing them at risk for liver-related death. The novel evidence that hypothalamic/pituitary dysfunction may be accompanied by progressive NAFLD has important implications for the work-up and management of patients with hypothalamic/pituitary disease.
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PMID:Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction. 1505 93

In obese humans and rodents there is increased expression of the key glucocorticoid (GC) regenerating enzyme, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), in adipose tissue. This increased expression appears to be of pathogenic importance because transgenic mice overexpressing 11beta-HSD1 selectively in adipose tissue exhibit a full metabolic syndrome with visceral obesity, dyslipidemia, insulin-resistant diabetes, and hypertension. In this model, while systemic plasma GC levels are unaltered, GC delivery to the liver via the portal vein is increased. 11beta-HSD1 is most highly expressed in liver where inhibition or deficiency of its activity improves glucose and lipid homeostasis. To determine the potential contribution of elevated intrahepatic GCs alone toward development of insulin-resistant syndromes we generated transgenic mice expressing increased 11beta-HSD1 activity selectively in the liver under transcriptional control of hepatic regulatory sequences derived from the human apoE gene (apoE-HSD1). Transgenic lines with 2- and 5-fold-elevated 11beta-HSD1 activity exhibited mild insulin resistance without altered fat depot mass. ApoE-HSD1 transgenic mice exhibited fatty liver and dyslipidemia with increased hepatic lipid synthesis/flux associated with elevated hepatic LXRalpha and PPARalpha mRNA levels as well as impaired hepatic lipid clearance. Further, apoE-HSD1 transgenic mice have a marked, transgene-dose-associated hypertension paralleled by incrementally increased liver angiotensinogen expression. These data suggest that elevated hepatic expression of 11beta-HSD1 may relate to the pathogenesis of specific fatty liver, insulin-resistant, and hypertensive syndromes without obesity in humans as may occur in, for example, myotonic dystrophy, and possibly, the metabolically obese, normal-weight individual.
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PMID:Metabolic syndrome without obesity: Hepatic overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in transgenic mice. 1511 95

The metabolic syndrome is intended to identify patients who have increased risk of diabetes and/or a cardiac event due to the deleterious effects of weight gain, sedentary lifestyle, and/or an atherogenic diet. The National Cholesterol Education Program's Adult Treatment Panel III definition uses easily measured clinical findings of increased abdominal circumference, elevated triglycerides, low high-density lipoprotein-cholesterol, elevated fasting blood glucose and/or elevated blood pressure. Three of these five are required for diagnosis. The authors also note that other definitions of metabolic syndrome focus more on insulin resistance and its key role in this syndrome. This review focuses on how treatment might affect each of the five components. Abdominal obesity can be treated with a variety of lower calorie diets along with regular exercise. Indeed, all of the five components of the metabolic syndrome are improved by even modest amounts of weight loss achieved with diet and exercise. For those with impaired fasting glucose tolerance, there is good evidence that a high fiber, low saturated fat diet with increased daily exercise can reduce the incidence of diabetes by almost 60%. Of note, subjects who exercise the most, gain the most benefit. Metformin has also been shown to be helpful in these subjects. Thiazolidinedione drugs may prove useful, but further studies are needed. Although intensified therapeutic lifestyle change will help the abnormal lipid profile, some patients may require drug therapy. This review also discusses the use of statins, fibrates, and niacin. Likewise, while hypertension in the metabolic syndrome benefits from therapeutic lifestyle change, physicians should also consider angiotensin converting enzyme inhibitor drugs or angiotensin receptor blockers, due to their effects on preventing complications of diabetes, such as progression of diabetic nephropathy and due to their effects on regression of left ventricular hypertrophy. Aspirin should be considered in those with at least a 10% risk of a coronary event over 10 years. Finally, three related conditions, nonalcoholic fatty liver disease, polycystic ovary syndrome and protease inhibitor associated lipodystrophy improve with therapeutic lifestyle change. Although metformin is shown to be useful with polycystic ovary syndrome, the data supporting drug therapy for the other syndromes is less convincing. More robust studies are needed before any firm recommendations can be made.
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PMID:Treatment of metabolic syndrome. 1515 70

Although there is a considerable interest of high-protein, low-carbohydrate diets to manage weight control, their safety is still the subject of considerable debate. They are suspected to be detrimental to the renal and hepatic functions, calcium balance, and insulin sensitivity. However, the long-term effects of a high-protein diet on a broad range of parameters have not been investigated. We studied the effects of a high-protein diet in rats over a period of 6 mo. Forty-eight Wistar male rats received either a normal-protein (NP: 14% protein) or high-protein (HP: 50% protein) diet. Detailed body composition, plasma hormones and nutrients, liver and kidney histopathology, hepatic markers of oxidative stress and detoxification, and the calcium balance were investigated. No major alterations of the liver and kidneys were found in HP rats, whereas NP rats exhibited massive hepatic steatosis. The calcium balance was unchanged, and detoxification markers (GSH and GST) were enhanced moderately in the HP group. In contrast, HP rats showed a sharp reduction in white adipose tissue and lower basal concentrations of triglycerides, glucose, leptin, and insulin. Our study suggests that the long-term consumption of an HP diet in male rats has no deleterious effects and could prevent metabolic syndrome.
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PMID:A long-term high-protein diet markedly reduces adipose tissue without major side effects in Wistar male rats. 1515 76

Dietary fish oil rich in (n-3) fatty acids plays an important role in reducing abnormalities associated with the metabolic syndrome and mortality from coronary heart disease. We investigated the effects of dietary fish oil on the metabolic syndrome in a high-sucrose-fed rat model. The model was achieved by the administration of 30% sucrose in drinking water in male Wistar rats during 21 weeks. After the metabolic syndrome rat model was established, fish oil was administered during 6 weeks. The metabolic syndrome rats showed significant increases in body weight, systolic blood pressure, serum insulin, total lipids, triacylglycerols, cholesterol, free fatty acids, LDL, total proteins, albumin, and serum tumor necrosis factor-alpha (TNF-alpha). They also presented abdominal and epididymal fat accumulation and fatty liver. After fish oil diet administration, metabolic syndrome rats had a significant reduction in blood pressure, serum insulin, triacylglycerols, cholesterol, free fatty acids, and total lipids, but no change was observed in TNF-alpha concentration or fat accumulation. In conclusion, fish oil reversed the alterations on metabolic parameters and blood pressure exerted by sucrose administration, although it had no effect on TNF-alpha production and adiposity. This confirms the theory that the molecular etiology of the metabolic syndrome is multifactorial, as is the effect of n-3 polyunsaturated fatty acids (PUFAs) upon it, having complex and multifaceted actions.
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PMID:Effects of fish oil on hypertension, plasma lipids, and tumor necrosis factor-alpha in rats with sucrose-induced metabolic syndrome. 1515 41


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