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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Life expectancy in the developed world is increasing, but this comes with a simultaneous explosion in 'age-related' as well as 'lifestyle-related' diseases, resulting in a decline in quality of life. Three such diseases are Type 2 diabetes mellitus (T2DM), Polycystic Ovarian Syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD), which all share a common reduced cellular response to the hormone insulin (termed insulin resistance). In T2DM, insulin resistance is clearly a contributing factor to disease progression, and is associated with obesity, the single greatest risk factor for all three conditions. Current research is focused on identifying the initial molecular lesion that results in reduced sensitivity to insulin, as improving insulin sensitivity would be beneficial to the prognosis of these conditions. However, the bulk of evidence suggests that more than one molecular defect in the insulin signalling pathway can lead to an insulin resistant phenotype. This raises the possibility that individuals with the same clinical phenotype may have distinct molecular reasons for the presence of the syndrome, and that the specific lesion influences the rate and direction of progression to the associated disease. Clearly the same insulin sensitiser could be of equal benefit in each disorder, if it reversed multiple signalling problems, however we suggest that appropriate molecular diagnosis of the defect may lead to a more targeted and effective therapeutic approach. This review discusses the molecular pathology of insulin resistance in relation to T2DM, PCOS and NASH. We highlight the shortcomings of current therapies, and suggest potential novel drug targets for each disorder.
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PMID:Dissecting insulin signaling pathways: individualised therapeutic targets for diagnosis and treatment of insulin resistant states. 1951 67

Hepatic steatosis is the most prevalent liver disorder in the developed world. It is closely associated with features of metabolic syndrome, especially insulin resistance and obesity. The two most common conditions associated with fatty liver are alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Liver biopsy is considered the gold standard for the assessment of liver fat, but there is a need for less invasive diagnostic techniques. New imaging modalities are emerging, which could provide more detailed information about hepatic tissue or even replace biopsy. In the present review, available imaging modalities (ultrasound, computed tomography, magnetic resonance imaging and proton magnetic resonance spectroscopy) are presented which are employed to detect or even quantify the fat content of the liver. The advantages and disadvantages of the above-mentioned imaging modalities are discussed. Although none of these techniques is able to differentiate between microvesicular and macrovesicular steatosis and to reveal all features visible using histology, the proposed diagnostic modalities offer a wide range of additional information such as anatomical and morphological information non-invasively. In particular, magnetic resonance imaging and proton magnetic resonance spectroscopy are able to quantify the hepatic fat content hence avoiding exposure to radiation. Except for proton magnetic resonance spectroscopy, all modalities offer additional information about regional fat distribution within the liver. MR elastography, which can estimate the amount of fibrosis, also appears promising in the differentiation between simple steatosis and steatohepatitis.
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PMID:Non-invasive assessment and quantification of liver steatosis by ultrasound, computed tomography and magnetic resonance. 1960 96

Metabolic syndrome (MS) is one of the most prevalent disease states in the so-called developed countries and is closely associated with the incidence of cardiovascular as well as other diseases. Predominant sign is the abdominal type of obesity with increased visceral fat mass and the associated insulin resistance. Glucose metabolism disorder, dyslipidemia and arterial hypertension are other important attributes. Metabolic syndrome is also closely associated with the liver steatosis, mostly benign and reversible liver disease. Nevertheless, uncomplicated steatosis may, under certain conditions, progress to inflammation and the disease may, through the stage of NASH (nonalcoholic steatohepatitis) and liver fibrosis, result in liver cirrhosis and hepatocellular carcinoma. Anglo-Saxon literature uses the term NAFLD (non-alcoholic fatty liver disease) to refer to these various stages ofthe liver disease (uncomplicated liver steatosis, steatohepatitis, fibrosis and cirrhosis). While simple steatosis is not dangerous for the patient, NASH is the sign of developing cirrhosis. Etiopathogenesis of NASH features identical characteristics as etiopathogenesis of insulin resistance and metabolic syndrome. Even though liver biopsy remains the gold standard in the diagnosis, new diagnostic approaches are emerging that could be useful in distinguishing simple steatosis from NASH. Therapy includes lifestyle changes, insulin resistance-reducing medication (also useful in the treatment of type 2 diabetes) with a range of other agents under development. In the meantime, randomized double-blind placebo-controlled studies with histological proof of the results are still lacking. A range of unresolved issues remains with regards to etiopathogenesis as well as diagnosis and treatment of NAFLD and NASH.
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PMID:[Metabolic syndrome and the liver (NAFLD/NASH)]. 1973 69

Resistin was originally described as an adipocyte-secreted peptide that induced insulin resistance in rodents. Increasing evidence indicates its important regulatory roles in various biological processes, including several inflammatory diseases. Further studies have shown that resistin in humans, in contrast to its production by adipocytes in mice, is synthesized predominantly by mononuclear cells both within and outside adipose tissue. Possible roles for resistin in obesity-related subclinical inflammation, atherosclerosis and cardiovascular disease, non-alcoholic fatty liver disease, rheumatic diseases, malignant tumors, asthma, inflammatory bowel disease, and chronic kidney disease have already been demonstrated. In addition, resistin can modulate several molecular pathways involved in metabolic, inflammatory, and autoimmune diseases. In this review, current knowledge about the functions and pathophysiological implications of resistin in different human pathologies is summarized, although there is a significant lack of firm evidence regarding the specific role resistin plays in the "orchestra" of the numerous mediators of inflammation.
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PMID:The role of resistin as a regulator of inflammation: Implications for various human pathologies. 1974 Jul 5

Excess lipid accumulation in nonadipose tissues may occur in the setting of high levels of plasma free fatty acids or triglycerides (TGs) in a process called "lipotoxicity". Evidence from human studies and animal models suggests that lipid accumulation in the heart, skeletal muscle, pancreas, and liver play an important role in the pathogenesis of heart failure, obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). During the past few years, several studies have shown that n-3 polyunsaturated fatty acids (PUFA) have potentially cardioprotective effects, especially in high-risk patients with dyslipidemia, and might therefore be expected to be of benefit in T2DM. Moreover, new information has demonstrated the beneficial effects of consuming n-3 PUFA in preventing the complications of lipotoxicity. n-3 PUFA dietary intake thus had positive effects on fatty liver in patients with non-alcoholic fatty liver disease (NAFLD), with an improvement in liver echotexture and a significant regression of hepatic brightness, associated with improved liver hemodynamics. The n-3 PUFA also had beneficial effects on ectopic fat accumulation inside the heart, with stabilization of cardiac myocytes and antiarrhythmic effects. On the other hand, recent data from animal models suggest that oral dosing of eicosapentaenoic acid (EPA) could contribute to protect against beta-cell lipotoxicity. This review discusses the latest hypotheses regarding lipotoxicity, concentrating on the impact of the n-3 PUFA that contribute to ectopic lipid storage, affecting organ function. Further human studies are needed to test the evidence and elucidate the mechanisms involved in this process.
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PMID:n-3 PUFA and lipotoxicity. 1978 63

The molecular basis for biological rhythms is formed by clock genes. Clock genes are functional in the liver, within gastrointestinal epithelial cells and neurons of the enteric nervous system. These observations suggest a possible role for clock genes in various circadian functions of the liver and the gastrointestinal tract through the modulation of organ specific clock-controlled genes. Consequently, disruptions in circadian rhythmicity may lead to adverse health consequences. This review will focus on the current understanding of the role of circadian rhythms in the pathogenesis of gastrointestinal- and hepatic disease such as obesity, non-alcoholic fatty liver disease, alcoholic fatty liver disease and alterations in colonic motility.
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PMID:Role of biological rhythms in gastrointestinal health and disease. 1979 81

Fifty years of the Gastroenterological Society of Australia have witnessed the changing appearance of Australians. Asian immigration has transformed the dominant urban culture from European to Eurasian, with some unique Australian attributes. Meanwhile, global conditions have altered body shape, and our sports-proud country is now fat! Thus, as in North America, Europe, China, and affluent Asia-Pacific countries, prosperity and lifestyle, cheap processed foods coupled with reduced physical activity have created an epidemic of over-nutrition resulting in overweight/obesity. Additional genetic factors are at the core of the apple shape (central obesity) that typifies over-nourished persons with metabolic syndrome. Indigenous Australians, once the leanest and fittest humans, now have exceedingly high rates of obesity and type 2 diabetes, contributing to shorter life expectancy; Asian Australians are also at higher risk. Like non-steroidal anti-inflammatory drugs (NSAIDs) and cigarette smoking, obesity now contributes much to gastrointestinal morbidity and mortality (gastroesophageal reflux disease, cancers, gallstones, endoscopy complications). This review focuses on Australian research about fatty liver, particularly roles of central obesity/insulin resistance in non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH). The outputs include many highly cited original articles and reviews and the first book on NAFLD. Studies have identified community prevalence, clinical outcomes, association with insulin resistance, metabolic syndrome and hypoadiponectinemia, developed and explored animal models for mechanisms of inflammation and fibrosis, conceptualized etiopathogenesis, and demonstrated that NASH can be reversed by lowering body weight and increasing physical activity. The findings have led to development of regional guidelines on NAFLD, the first internationally, and should now inform daily practice of gastroenterologists.
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PMID:The liver and the waistline: Fifty years of growth. 1979 88

Metabolic consequences of obesity including insulin resistance, type 2 diabetes mellitus, hyperlipidemia, hypertension, polycystic ovarian syndrome, and non-alcoholic fatty liver infiltration are rapidly emerging in the pediatric population. Identifying effective strategies for identifying and treating these obesity related comorbidities in children are crucial to the prevention of future cardiovascular disease and poor health outcomes.This review discusses the pathophysiologic connections between obesity, metabolic disease and cardiovascular risk. Current evidence and recommendations for screening and treatment for the metabolic consequences of pediatric obesity are reviewed.
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PMID:Identification and treatment of metabolic complications in pediatric obesity. 1980 79

As the worldwide obesity epidemic continues to increase, the prevalence of non-alcoholic fatty liver disease (NAFLD) and specifically non-alcoholic steatohepatitis (NASH) will become increasingly prominent. NASH will surpass chronic hepatitis C infection as the primary indication for orthotopic liver transplantation in the near future. With the evolution of surgical techniques, bariatric surgery is currently recognized as the most effective method for achieving sustained weight loss and reversing numerous comorbidities in severely obese individuals. This review focuses on the potential risks and benefits of bariatric surgery in subjects with NAFLD and explores its role in the management of NASH in the obese patient.
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PMID:Non-alcoholic fatty liver disease: is bariatric surgery the answer? 1981 13

The metabolic disorders that predispose patients to NASH (non-alcoholic steatohepatitis) include insulin resistance and obesity. Repeated hypoxic events, such as occur in obstructive sleep apnoea syndrome, have been designated as a risk factor in the progression of liver disease in such patients, but the mechanism is unclear, in particular the role of hypoxia. Therefore we studied the influence of hypoxia on the development and progression of steatohepatitis in an experimental mouse model. Mice with a hepatocellular-specific deficiency in the Pten (phosphatase and tensin homologue deleted on chromosome 10) gene, a tumour suppressor, were exposed to a 10% O2 (hypoxic) or 21% O2 (control) atmosphere for 7 days. Haematocrit, AST (aspartate aminotransferase), glucose, triacylglycerols (triglycerides) and insulin tolerance were measured in blood. Histological lesions were quantified. Expression of genes involved in lipogenesis and mitochondrial beta-oxidation, as well as FOXO1 (forkhead box O1), hepcidin and CYP2E1 (cytochrome P450 2E1), were analysed by quantitative PCR. In the animals exposed to hypoxia, the haematocrit increased (60+/-3% compared with 50+/-2% in controls; P<0.01) and the ratio of liver weight/body weight increased (5.4+/-0.2% compared with 4.7+/-0.3% in the controls; P<0.01). Furthermore, in animals exposed to hypoxia, steatosis was more pronounced (P<0.01), and the NAS [NAFLD (non-alcoholic fatty liver disease) activity score] (8.3+/-2.4 compared with 2.3+/-10.7 in controls; P<0.01), serum AST, triacylglycerols and glucose were higher. Insulin sensitivity decreased in mice exposed to hypoxia relative to controls. The expression of the lipogenic genes SREBP-1c (sterol-regulatory-element-binding protein-1c), PPAR-gamma (peroxisome-proliferator-activated receptor-gamma), ACC1 (acetyl-CoA carboxylase 1) and ACC2 (acetyl-CoA carboxylase 2) increased significantly in mice exposed to hypoxia, whereas mitochondria beta-oxidation genes [PPAR-alpha (peroxisome-proliferator-activated receptor-alpha) and CPT-1 (carnitine palmitoyltransferase-1)] decreased significantly. In conclusion, the findings of the present study demonstrate that hypoxia alone aggravates and accelerates the progression of NASH by up-regulating the expression of lipogenic genes, by down-regulating genes involved in lipid metabolism and by decreasing insulin sensitivity.
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PMID:Hypoxia aggravates non-alcoholic steatohepatitis in mice lacking hepatocellular PTEN. 1983 98


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