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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is a principal causative factor in the development of metabolic syndrome. Here we report that increased oxidative stress in accumulated fat is an important pathogenic mechanism of obesity-associated metabolic syndrome. Fat accumulation correlated with systemic oxidative stress in humans and mice. Production of ROS increased selectively in adipose tissue of obese mice, accompanied by augmented expression of NADPH oxidase and decreased expression of antioxidative enzymes. In cultured adipocytes, elevated levels of fatty acids increased oxidative stress via NADPH oxidase activation, and oxidative stress caused dysregulated production of adipocytokines (fat-derived hormones), including adiponectin, plasminogen activator inhibitor-1, IL-6, and monocyte chemotactic protein-1. Finally, in obese mice, treatment with NADPH oxidase inhibitor reduced ROS production in adipose tissue, attenuated the dysregulation of adipocytokines, and improved diabetes, hyperlipidemia, and hepatic steatosis. Collectively, our results suggest that increased oxidative stress in accumulated fat is an early instigator of metabolic syndrome and that the redox state in adipose tissue is a potentially useful therapeutic target for obesity-associated metabolic syndrome.
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PMID:Increased oxidative stress in obesity and its impact on metabolic syndrome. 1559

The global emergence of obesity as an epidemic has made fatty liver disease a public health problem in the Western world. The increased incidence of obesity has been paralleled by an increase in metabolic syndrome in the same cohort of patients. The net consequence of insulin resistance in a large majority of these obese individuals is hepatic steatosis, which over time in a proportion of these patients progresses to steatohepatitis and cirrhosis. Despite the increased awareness among physicians regarding its presence, the diagnostic process has been hampered by the lack of sensitive and specific population-based screening tests. Liver biopsy remains the gold standard for diagnosis as well as for grading and staging of the disease process but its precise role in the diagnostic conundrum continues to be debated.
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PMID:Clinical aspects of fatty liver disease. 1560 3

Obesity-related liver disease, particularly nonalcoholic fatty liver disease and its more severe form nonalcoholic steatohepatitis, is being increasingly recognized as a common liver disease in developed countries and represents hepatic manifestation of the metabolic syndrome. Nonalcoholic steatohepatitis results in progressive fibrosis, cirrhosis, and end-stage liver disease, with its increased incidence of hepatocellular carcinoma. Liver biopsy remains the gold standard in detection, evaluation, staging, and grading of nonalcoholic steatohepatitis. Liver biopsy also provides an important tool to detect concomitant liver disease that may accelerate the progression of steatohepatitis in these patients. Surgical or drug-induced weight loss has been documented to reduce the amount of inflammation, to induce regression of fibrosis, and, in some cases, to cause a reversal of cirrhosis in obese patients with steatohepatitis. Pretreatment or intraoperative liver biopsy should be performed to assess the presence of steatohepatitis, and stage and grade of steatohepatitis. This article will discuss obesity-related liver diseases, focusing on pathologic features in liver biopsies from obese patients, obesity-related hepatocellular carcinoma, and the effect of weight loss treatment on histopathology.
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PMID:Liver pathology in obesity. 1560 4

Hepatitis C virus (HCV) and nonalcoholic fatty liver disease (NAFLD) are the two most common causes of chronic liver disease in North America. NAFLD represents a spectrum of liver lesions that occur in individuals who either do not consume any alcohol or only consume alcohol in quantities generally considered not to be harmful to the liver. This spectrum consists of isolated hepatic macrovesicular steatosis at one end and nonalcoholic steatohepatitis (NASH) at the other. Hepatic steatosis is present in approximately 50% of the subjects with HCV. Genotype 3 is independently associated with hepatic steatosis. In those with genotype 1 infection, steatosis is associated with features of the metabolic syndrome. The presence of hepatic steatosis correlates with the stage of hepatic fibrosis in patients with HCV. This has been related to the presence of insulin resistance. Hepatic steatosis also adversely affects the virologic response rates to anti-HCV therapy. In this article, we will review the epidemiology of HCV and NAFLD, their impact on each other, and the course of the liver disease in individuals afflicted with both conditions.
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PMID:Hepatitis C and nonalcoholic fatty liver disease. 1560 8

Diabetes mellitus is the fifth leading cause of death in the United States; 17 million people are affected. Liver disease is one of the leading causes of death in persons with type 2 diabetes. The standardized mortality rate for death from liver disease is greater than that for cardiovascular disease. The spectrum of liver disease in type 2 diabetes ranges from nonalcoholic fatty liver disease to cirrhosis and hepatocellular carcinoma. The incidence of hepatitis C and acute liver failure is also increased. Nonalcoholic fatty liver disease is now considered part of the metabolic syndrome, and, with alcohol and hepatitis C, is the most common cause of chronic liver disease in the United States. Weight reduction and exercise are the mainstays of treatment for nonalcoholic fatty liver disease, but there are promising results with the new thiazolidinediones (pioglitazone and rosiglitazone) as well as metformin and 3-hydroxy-3-methylglutaryl coenzyme A inhibitors.
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PMID:Narrative review: hepatobiliary disease in type 2 diabetes mellitus. 1561 92

Adiponectin, secreted specifically from adipocytes, is thought to play a key role in the metabolic syndrome. Plasma adiponectin concentrations were studied in 36 typical nonalcoholic fatty liver (NAFL) women which is commonly associated with the metabolic syndrome. They were diagnosed as NAFL by ultrasound brightness, slightly elevated serum ALT levels and the exclusion of history of alcohol abuse and other known liver diseases. Compared with 64 control women, NAFL had a significant increase in the variables of the metabolic syndrome, other hepatic enzymes and leptin levels, while a reduction in AST/ALT ratio and adiponectin before (mean +/- SE: 7.2 +/- 0.5 vs 9.0 +/- 0.4 microg/ml, p < 0.005) and after adjustment for body fat mass (0.24 +/- 0.02 vs 0.34 +/- 0.02, p < 0.0001), atherogenic Index [(total cholesterol - HDLC)/HDLC: 3.2 +/- 0.3 vs 4.6 +/- 0.3, p < 0.005] or calculated insulin resistance (HOMA-R) (6.6 +/- 1.9 vs 8.6 +/- 0.9, p < 0.005). BMI and amylase were positive, and adiponectin/BMI was negative significant independent determinants of ALT value in multiple regression model. In conclusion, while hypoadiponectinemia was observed in NAFL, hypoadiponectinemia provides the possibility of fat accumulation in the liver.
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PMID:Plasma adiponectin decrease in women with nonalcoholic Fatty liver. 1564 78

The metabolic syndrome has been characterized by a cluster of abnormalities that include obesity, hyperglycemia, dyslipidemia, and hypertension. Other conditions associated with this syndrome include microalbuminuria, inflammation, a prothrombotic state, and a fatty liver. Together, these abnormalities lead to an environment where the risk of developing both type 2 diabetes and atherosclerotic cardiovascular disease are greatly enhanced. Recognition of this syndrome by practitioners, early treatment, and long-term management are crucial for disease prevention. Successful treatment requires the introduction of lifestyle changes initially and pharmacotherapy subsequently if lifestyle changes are not sufficient.
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PMID:Pathophysiology and long-term management of the metabolic syndrome. 1568 14

The aromatase (ArKO) knockout mouse develops obesity marked by increased gonadal fat depots. This obesity is characterized by pronounced hypertrophy and hyperplasia in adipocytes with corresponding increases in transcripts involved in fat development. Aromatase deficiency in mice and humans with natural mutations of the aromatase gene also leads to metabolic syndrome, particularly hepatic steatosis. In ArKO mice, this hepatic steatosis, the increased body weight and serum triglycerides are surprisingly prevented by cholesterol feeding. We sought to investigate whether the reduction in body weight upon cholesterol feeding is reflected in gonadal fat depots, which account for a large percentage of body weight in the ArKO mouse. Indeed, gonadal fat depots in female ArKO mice were significantly reduced after cholesterol feeding. Concomitantly, adipocyte hyperplasia and hypertrophy were dramatically reduced upon cholesterol feeding in ArKO mice. Real-time PCR analysis revealed concurrent changes with adipocyte volume in the levels of lipoprotein lipase, caveolin-1 and CD59 transcripts. Little change was observed in levels of transcripts involved in de novo fatty acid synthesis, beta-oxidation, lipolysis, differentiation and cholesterol metabolism, suggesting that cholesterol feeding prevents hyperplasia and hypertrophy of ArKO adipocytes, possibly as a consequence of changes in transcript levels of lipoprotein lipase and therefore fatty acid uptake.
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PMID:Cholesterol feeding prevents adiposity in the obese female aromatase knockout (ArKO) mouse. 1570 35

Peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of the nuclear hormone receptor family, is a master regulator of adipogenesis. Humans with dominant negative PPARgamma mutations have features of the metabolic syndrome (severe insulin resistance, dyslipidemia, and hypertension). We created a knock-in mouse model containing a potent dominant negative PPARgamma L466A mutation, shown previously to inhibit wild-type PPARgamma action in vitro. Homozygous PPARgamma L466A knock-in mice die in utero. Heterozygous PPARgamma L466A knock-in (PPARKI) mice exhibit hypoplastic adipocytes, hypoadiponectinemia, increased serum-free fatty acids, and hepatic steatosis. When subjected to high fat diet feeding, PPARKI mice gain significantly less weight than controls. Hyperinsulinemic-euglycemic clamp studies in PPARKI mice revealed insulin resistance and reduced glucose uptake into skeletal muscle. Female PPARKI mice exhibit hypertension independent of diet. The PPARKI mouse provides a novel model for studying the relationship between impaired PPARgamma function and the metabolic syndrome.
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PMID:A dominant negative peroxisome proliferator-activated receptor-gamma knock-in mouse exhibits features of the metabolic syndrome. 1571 67

We performed a cross-sectional study of newly diagnosed cases of nonalcoholic fatty liver disease (NAFLD) identified between December 1998 and December 2000 in the Chronic Liver Disease Surveillance Study. We compared the demographic and clinical features of NAFLD in a racially diverse representative U.S. population (Alameda County, CA). Diagnostic criteria for probable NAFLD were persistent unexplained elevation of serum aminotransferase levels, radiology (ultrasound or computed tomography scan) consistent with fatty liver, and/or two or more of the following: (i) body mass index of 28 kg/m(2) or more, (ii) type 2 diabetes, or (iii) hyperlipidemia, in the absence of significant alcohol use. Definite NAFLD cases required histological confirmation. Of the 742 persons with newly diagnosed chronic liver disease, 159 (21.4%) had definite or probable NAFLD. The majority were nonwhite: Hispanics (28%), Asians (18%), African Americans (3%), and other race(s) (6%). African Americans with NAFLD were significantly older than other racial or ethnic groups (P < .001), and in Asians, NAFLD was 3.5 times more common in males than in females (P = .016). Clinical correlates of NAFLD (obesity, hyperlipidemia, diabetes) were similar among racial and ethnic groups, except that body mass index was lower in Asians compared with other groups (P < .001). Compared with the base population (Kaiser Permanente members), Hispanics with NAFLD were overrepresented (28% vs. 10%) and whites were underrepresented (45% vs. 59%). In conclusion, these racial and gender variations may reflect differences in genetic susceptibility to visceral adiposity, including hepatic involvement, and may have implications for the evaluation of persons with the metabolic syndrome. Clinicians need to be aware of the variable presentations of NAFLD in different racial and ethnic groups.
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PMID:Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease. 1572 36


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