Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-alcoholic steatohepatitis is a chronic disease that occurs in persons without significative consumption of alcohol, characterized by macrovesicular steatosis, mixed inflammatory infiltrate, and diverse degrees of fibrosis. It can progress to cirrhosis and its evolution to hepatocellular carcinoma has been described. It principally occurs in patients with obesity, diabetes mellitus, and hyperlipidemia, and is at present considered a manifestation of metabolic syndrome with insulin resistance. In pathogenesis, diverse factors, fundamentally insulin resistance as a mechanism that determines hepatic steatosis, have been described. Later, alteration of signalling cascades, oxidative stress, and other mechanisms occur that lead to inflammation, necrosis, and finally to hepatic fibrosis, the details of which will be described in this review.
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PMID:[Pathogenic molecular mechanisms in non-alcoholic steatohepatitis]. 1575 91

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease observed in the clinical practice of hepatology. The coexistence of metabolic syndrome in this cohort of patients has made insulin resistance central to the pathogenesis of these disorders. The metabolic consequence of insulin resistance is impaired hepatic glucose output and abnormal lipid handling. In the face of continued metabolic insults the normal hepatic regulatory mechanism gets overwhelmed and fat accumulates in the hepatocytes. The subsequent fate of steatotic hepatocytes depends on the capacity of additional factors such as adipocytokines and toxicity induced by the free fatty acids themselves to induce inflammatory response. This latter process is responsible for the producing the phenotype of non-alcoholic steatohepatitis (NASH). Irrespective of the process by which these phenotypic response occurs, it is now universally accepted that in the absence of insulin resistance the spectrum of changes one associates with NAFLD does not develop. In this review we will discuss the various processes that are involved in the pathogenesis of NAFLD.
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PMID:Insulin resistance in NASH. 1576 42

Nonalcoholic fatty liver disease is emerging as the most common chronic liver condition in the Western world. It is associated with insulin resistance and frequently occurs with features of the metabolic syndrome. Disease presentation ranges from asymptomatic elevated liver enzyme levels to cirrhosis with complications of liver failure and hepatocellular carcinoma. Current treatment recommendations are limited to weight loss and exercise, although several promising medications are on the horizon. In this article we discuss the etiology, pathogenesis and diagnosis of nonalcoholic fatty liver disease as well as approaches to its management.
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PMID:Nonalcoholic fatty liver disease. 1618 72

Nonalcoholic fatty liver disease (NAFLD) is a component of the metabolic syndrome, with a clinical spectrum ranging from simple fatty liver to steatohepatitis, cirrhosis, and hepatocellular carcinoma. The primary event of NAFLD is the accumulation of triacylglycerols (TAGs) in hepatocytes. In this issue of the JCI, Donnelly et al. report on their use of stable isotope methodology to show that fatty acids stored in adipose tissue and fatty acids newly made within the liver through de novo lipogenesis are the major sources of TAGs in the liver and are secreted as lipoproteins in NAFLD.
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PMID:Contribution of adipose tissue and de novo lipogenesis to nonalcoholic fatty liver disease. 1586 52

Non-alcoholic steatohepatitis (NASH) represents only a part of a wide spectrum of non-alcoholic fatty liver disease (NAFLD) and its prevalence is only 2 - 3% in the general population. Obesity, diabetes, hyperlipidemia and female sex are important risk factors for NASH. Two hit theory describes very well the pathogenesis of NASH wherein hepatic steatosis, the first hit is followed up by the second hit, one of which may be reactive oxygen species. Mitochondria is the main source of reactive oxygen species which may trigger steatohepatitis by lipid peroxidation, cytokine induction or induction of fas-ligand. Insulin resistance syndrome is the only metabolic syndrome that has been consistently associated with NASH. The diagnosis rests on the hallmark histological features and rigorous exclusion of significant alcohol consumption. Most patients are asymptomatic, have mild-to-moderate elevations of serum aminotransferase levels, clinical hepatomegaly and features of fatty liver on imaging. Liver biopsy is essential for positive diagnosis and prognostication of NASH. Histologically, fat deposition is typically macrovesicular and inflammation of steatohepatitis is predominantly lobular. Neutrophilic cells in lobular inflammatory infilterate are a distinguishing feature of steatohepatitis and differentiate it from other chronic hepatitis. The pattern of collagen deposition is perivenular & peri-sinusoidal spaces in zone 3. NASH is a progressive disease in more than one in four and has spontaneous regression in less than one in six. Therapy options include weight reduction in obese, good control in diabetics and exercise. Ursodeoxycholic acid has membrane stabilizing, cytoprotective and immunological effect and normalizes raised transaminases. Liver transplantation has been done in NASH but transplanted liver shows re-development in more than two thirds. Many more therapies are in the pipeline and show promise for the future.
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PMID:Non-alcoholic steatohepatitis. 1592 3

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in developing countries. Many of the risk factors are well defined, but the underlying pathogenesis is not well understood. The demographics of the condition mirror those of the metabolic syndrome, with obesity and insulin resistance being the most commonly associated conditions. At present, therapy is aimed at correcting the risk factors, but there are no proven therapies at this point.
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PMID:Therapeutic strategies in nonalcoholic fatty liver disorders. 1593 65

Non-alcoholic fatty liver disease (NAFLD) has become the most common form of hepatic disorders in the developed world. NAFLD is part of the metabolic syndrome with insulin resistance as a primary underlying derangement. The natural history of NAFLD may extend from simple steatosis over steatohepatitis into cirrhosis and hepatocellular carcinoma. Among numerous factors shaping these transitions, uncoupling protein-2 (UCP2) may theoretically contribute to every stage of this disease. UCP2 is a recently identified fatty acid-responsive mitochondrial inner membrane carrier protein showing wide tissue distribution with a substantially increased presence in fatty liver. The biological functions of UCP2 are not fully elucidated and the greater part of our current knowledge has been obtained from animal experiments. These data suggest a role for UCP2 in lipid metabolism, mitochondrial bioenergetics, oxidative stress, apoptosis, and even carcinogenesis. Available evidence is reviewed and new concepts are considered to appraise the potential role of UCP2 in the pathogenesis of NAFLD.
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PMID:Uncoupling protein-2 and non-alcoholic fatty liver disease. 1597 Apr 80

Nonalcoholic fatty liver disease (NAFLD) is consistently associated with features of the metabolic syndrome, a condition carrying a high risk of cardiovascular events. We measured the vasodilatory response of the brachial artery in response to ischemia (a test of endothelial function) (FMV) as well as cardiovascular risk profile in 52 NAFLD cases and 28 age- and sex-matched controls. The 10-year risk of coronary events was calculated according to the Framingham equation and the scores derived from the PROCAM study and NCEP-ATPIII proposals. FMV was 6.33% +/- 5.93% in NAFLD versus 12.22% +/- 5.05% in controls (P < .0001), and higher in pure fatty liver (9.93%) compared with nonalcoholic steatohepatitis (4.94%) (P = .010). No differences were observed in flow-independent vasodilation (response to sublingual nitroglycerin). Percent FMV was negatively associated with insulin resistance (homeostasis model assessment) in the whole population (r = -0.243; P = .030). In logistic regression analysis, NAFLD was associated with a percent FMV in the lower tertile (OR, 6.7; 95% CI, 1.26-36.1), after adjustment for age, sex, body mass index, and insulin resistance. Among NAFLD patients, low FMV was associated with nonalcoholic steatohepatitis (adjusted OR, 6.8; 95% CI, 1.2-40.2). The 10-year probability of cardiovascular events was moderately increased in NAFLD, and particularly in nonalcoholic steatohepatitis. In conclusion, our study provides evidence of endothelial dysfunction and increased risk of cardiovascular events in NAFLD. The risk of advanced liver disease is well recognized in NAFLD patients, but the large majority of cases might experience cardiovascular disease in the long term, indirectly limiting the burden of liver failure.
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PMID:Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. 1617 89

The incidence of hepatocellular carcinoma is increasing, but the temporal changes of risk factors remain unclear. A significant proportion of hepatocellular carcinoma (7-30%) develops in cryptogenic cirrhosis, and may represent the most worrisome complication of non-alcoholic steatohepatitis. Non-alcoholic steatohepatitis is tightly related to insulin resistance and several features of the metabolic syndrome, i.e obesity, type 2 diabetes and dyslipidaemia. Nearly two-thirds of adults in the United States and an increasing percentage of the population worldwide are overweight or obese. Diabetes prevalence is increasing as well. The rising prevalence of risk factors associated with non-alcoholic steatohepatitis can partially account for the increasing incidence of cryptogenic cirrhosis and subsequent hepatocellular carcinoma. Moreover, recent evidence demonstrates that both obesity and diabetes are per se associated with an increased cancer risk. Large prospective studies show a significant association with obesity for several cancers, including cancers of the colon, female breast, endometrium, kidney, oesophagus and liver (hepatocellular carcinoma). Type 2 diabetes is also related with increased risks of colon, endometrial, kidney, pancreatic cancer and hepatocellular carcinoma. In western countries, the insulin resistance syndrome is emerging as a risk factor for a wide variety of cancers, including hepatocellular carcinoma.
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PMID:Review article: steatosis, the metabolic syndrome and cancer. 1622 71

Nonalcoholic fatty liver disease (NAFLD) refers to a wide picture of liver damage, ranging from steatosis to steatohepatitis, fibrosis and cirrhosis. The epidemiological studies demonstrated an association of NAFLD with obesity, type 2 diabetes and hyperlipidemia. Under this light the metabolic syndrome (MS), including NAFLD, obesity, central fat distribution, diabetes, dyslipidemia, hypertension and atherosclerotic cardiovascular disease (CVD) can be considered the link to explain the presence of vascular diseases in patients with NAFLD. In NHANES III, the authors demonstrated that the presence of MS was associated with increased risk of myocardial infarction, stroke or both. In a prospective study on 1209 Finnish middle-aged men without CVD or diabetes at baseline, Lakka showed that MS per se is associated with an increased risk of CVD and all-cause mortality. Finally the Atherosclerosis Risk in Communities (ARIC) confirmed that subjects with MS were 2 times more likely to have prevalent coronary heart disease. From a pathophysiological point of view, growing evidences implicate the oxidative stress as the unifying mechanism for many CVD risk factors. Under this light there is emerging evidence suggesting that there is a significant increase in vascular oxidative stress in patients with MS, with the presence of endothelial dysfunction in the early stage of the syndrome. Indeed, the inflammation process evidentiated in these patients is initiated at the endothelial level, stressing the key role of this active and dynamic tissue in the pathophysiological pathways. Under this light the endothelium can be considered as the last effector of a multi-syndrome and the main target of all the future studies focused on the underlying mechamisms of this complex network. Because of the potential serious public health impact, the comprehension of these patophysiological pathways will be crucial to design new preventive measures and therapeutic strategies.
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PMID:Hepatic steatosis and vascular disease. 1623 88


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