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

Alcoholic liver disease (ALD) is characterized by accumulation of neutral lipids in hepatocytes leading to micro and macro-vesicular steatosis and balloon cell degeneration. Hypercaloric alimentation and resultant obesity also cause similar changes as evident in non-alcoholic fatty liver disease (NAFLD). Thus, accumulation of lipids in hepatocytes is a pathologic hallmark of ALD and NAFLD. In contrast, quiescent hepatic stellate cells (HSC) are characterized by the intracellular content of not only vitamin A but also triglycerides, and HSC activation is associated with depletion of these lipids. In fact, our recent work demonstrates that adipogenic/ lipogenic transcriptional regulation rendered by PPARgamma, LXRa, and SREBP-1c is essential for the maintenance of the fat-storing, quiescence phenotype of HSC. Expression of these adipogenic transcription factors is lost in activated HSC and the treatment of the cells with the adipocyte differentiation cocktail or ectopic expression of PPARgamma or SREBP-1c causes a reversal of activated cells to the quiescent phenotype. In steatotic livers from ALD and NAFLD mouse models, the expression of these adipogenic transcription factors is induced while the normal control livers lack such expression. Thus, adipogenic regulation is essential for HSC quiescence while it makes hepatocytes steatotic. Interestingly, under the adipogenic conditions of ALD and NAFLD, HSC are still activated to cause fibrosis. This fat paradox in hepatocytes and HSC highlights contrasted significance of fat in these two cell types that depend on each other for their homeostatic control. It further suggests, activated HSC in steatotic livers may have defective insulin signaling or lipogenic regulation.
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PMID:Fat paradox in liver disease. 1645 29

Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of fat-induced liver injury, ranging from relatively benign steatosis to cirrhosis and liver failure. The presence of obesity and insulin resistance is strongly associated with non-alcoholic fatty liver and confers on it a greater risk of histologically advanced disease. There is a growing concern in the medical profession as the prevalence of this disease continues to rise in parallel with the rise in obesity and the metabolic syndrome. Treatment options are limited and dietary weight loss is often advised. Low fat diets are difficult to adhere to and recent studies have shown the potential of low carbohydrate diets for weight loss and improving insulin resistance. Thus far, no study has evaluated the effect of low carbohydrate diets on NAFLD. Future studies will be required to address this question and others with regards to the nutritional adequacy and long-term side effects of these diets.
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PMID:Non-alcoholic fatty liver disease and the metabolic syndrome: effects of weight loss and a review of popular diets. Are low carbohydrate diets the answer? 1648 32

Non-alcoholic fatty liver disease is considered a component of the metabolic syndrome associated with obesity. Problems still exist concerning non-alcoholic fatty liver disease patients in clinical practice, for example: (a) how to diagnose non-alcoholic fatty liver disease and its type; (b) how to select patients candidate to treatment; (c) how to treat selected patients. Non-alcoholic fatty liver disease includes steatosis and non-alcoholic steatohepatitis, but only non-alcoholic steatohepatitis evolves into cirrhosis and the absolute risk of mortality for non-alcoholic fatty liver disease is low. As yet, no tools, other than liver biopsy, are available to differentiate the various types of non-alcoholic fatty liver disease. Many drugs are, currently, under study to treat non-alcoholic fatty liver disease, even if well-performed trials are until necessary to define the best treatment. At the moment, the entity of the problem and the characteristics of patients frequently put the physician, in clinical practice, to choose the therapeutic approach arbitrarily which is considered more effective for each individual patient. Probably the future will consider the possibility of treating non-alcoholic fatty liver disease with more than one drug, by considering the various aspects and degree of this syndrome. Actually each physician should select the individual treatment on the basis of his/her knowledge and experience, by never forgetting the old saying 'primum non nocere'. However, the epidemiological entity of the problem, the characteristics of the patients, generally young, the frequent lack of clinical evidence of involvement of the liver, are all the factors that require vast well-performed clinical trials in order to define the best therapeutic approach for each individual patient.
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PMID:Treatment of patients with non-alcoholic fatty liver disease: current views and perspectives. 1675 Jun 61

In the past two decades, cannabinoids have emerged as crucial mediators in a variety of pathophysiological conditions. Awareness of their critical functions in liver pathophysiology is only recent, probably given the low level of expression of cannabinoid receptor type 1 (CB1 receptor) and type 2 (CB2 receptor) in normal liver. However, it has been shown that non-alcoholic fatty liver disease and cirrhosis are associated to a marked upregulation of the hepatic endocannabinoid system, including increases in endocannabinoids and in hepatic CB receptors, both in humans and in rodents. Consequently, a growing number of cannabinoid-related hepatic effects are being unravelled. Hence, hepatic CB1 receptors enhance liver steatogenesis in a mouse model of high fat-induced obesity, and contribute to peripheral arterial vasodilation in cirrhosis, thereby promoting portal hypertension. In addition, CB1 and CB2 receptors elicit dual opposite effects on fibrogenesis associated to chronic liver injury, by promoting pro- and antifibrogenic effects, respectively. Therefore, endocannabinoid-based therapies may open novel therapeutic avenues in the treatment of chronic liver diseases.
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PMID:Endocannabinoids as novel mediators of liver diseases. 1675 9

Obesity is a major risk factor for the development of the metabolic syndrome, a cluster of diseases including insulin resistance, type 2 diabetes, dyslipidemia, hypertension, microalbuminuria, atherosclerosis, and non-alcoholic steatohepatitis. On the other hand, it is now generally accepted that adipose tissue acts as an endocrine organ producing a number of substances with an important role in the regulation of food intake, energy expenditure and a series of metabolic processes. Adiponectin is a recently discovered hormone produced exclusively by adipocytes. In fact, adiponectin is considered currently as a major factor in obesity-related insulin resistance and atherosclerosis. This new hormone differs from other adipocytokines in that its production and concentrations are actually decreased in insulin resistant subjects. The aim of this review is to summarize the current knowledge about the chemistry and physiology of adiponectin and to discuss its implications in the pathophysiology and potential treatment of insulin resistance and non-alcoholic fatty liver disease.
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PMID:Adiponectin, structure, function and pathophysiological implications in non-alcoholic fatty liver disease. 1678 75

The prevalence of obesity and diabetes has reached pandemic proportions. Obesity, particularly in association with high waist circumference and high BMI, is an independent risk factor for coronary heart disease (CHD) and diabetes. Several large studies have shown that marginal (5 lb) to moderate (11 to 22 lb) weight gain in adulthood (age 20 to 50 years) increases the risk of chronic disease and negatively affects CHD risk status. The metabolic syndrome, a clustering of cardiovascular and metabolic risk factors that includes abdominal obesity, is increasing among adults and children and is strongly associated with the development of diabetes and CHD. Recent evidence suggests that elevated liver enzymes, an indicator of non-alcoholic fatty liver disease, may comprise an additional component of the metabolic syndrome and may serve as a surrogate marker for type 2 diabetes, particularly if used in conjunction with C-reactive protein.
Obesity (Silver Spring) 2006 Jun
PMID:Relationship of metabolic risk factors and development of cardiovascular disease and diabetes. 1693 93

Immigration, cheap air travel, and globalization are all factors contributing to a worldwide spread of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. End-stage chronic liver disease (ESLD) as a result of co-infection with HBV/HCV is now the major cause of death for individuals who have been infected with the HIV virus. The high incidence of HCV infection in Egypt--the legacy left from the mass use of tartar emetic to eradicate schistosomiasis, as in other high prevalence areas--will take years to reduce. Steatohepatitis due to non-alcoholic fatty liver disease is developing into a new and major health problem as a result of rising levels of obesity in populations worldwide. Hepatic steatosis also has an adverse influence on the progression of other liver diseases including chronic HCV infection and alcoholic liver disease. In many countries, considerable public concern is on the rise due to increased levels of alcohol consumption adversely affecting younger and affluent age groups. With the rising prevalence of cirrhosis, primary hepatocellular carcinoma (HCC) is increasing in frequency as is that of primary intrahepatic cholangiocarcinoma. Finally, despite the successes of liver transplantation, many deserving patients are not getting transplants due to low levels of cadaver organ donation in many countries, thereby increasing pressures on the use of living donor liver transplantation. Only through a concerted effort from governments, health agencies, healthcare professionals at all levels, and the pharmaceutical industry can this grim outlook for liver disease worldwide be reversed.
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PMID:Global challenges in liver disease. 1694 87

While the vast majority of heavy drinkers and individuals with obesity, insulin resistance, and the metabolic syndrome will have steatosis, only a minority will ever develop steatohepatitis, fibrosis, and cirrhosis. Genetic and environmental risk factors for advanced alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) seem likely to include factors that influence the severity of steatosis and oxidative stress, the cytokine milieu, the magnitude of the immune response, and/or the severity of fibrosis. For ALD, the dose and pattern of alcohol intake, along with obesity are the most important environmental factors determining disease risk. For NAFLD, dietary saturated fat and antioxidant intake and small bowel bacterial overgrowth may play a role. Family studies and interethnic variations in susceptibility suggest that genetic factors are important in determining disease risk. For ALD, functional polymorphisms in the alcohol dehydrogenases and aldehyde dehydrogenase alcohol metabolising genes play a role in determining susceptibility in Oriental populations. No genetic associations with advanced NAFLD have been replicated in large studies. Preliminary data suggest that polymorphisms in the genes encoding microsomal triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin receptor, TNF-alpha, transforming growth factor-beta, and angiotensinogen may be associated with steatohepatitis and/or fibrosis.
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PMID:Genes or environment to determine alcoholic liver disease and non-alcoholic fatty liver disease. 1703 1

Studies have revealed that high-fat (HF) diets promote hyperglycaemia, whole-body insulin resistance and non-alcoholic fatty liver disease (NAFLD). Recently, hepatic glucagon resistance has been shown to occur in rats fed a HF diet. More precisely, diet-induced obesity (DIO) reduces the number of hepatic plasma membrane glucagon receptors (GR), which results in a diminished response to glucagon during a hyperglucagonaemic clamp. The present study was undertaken to test the hypothesis that a HF-DIO is associated with a desensitization and destruction of the hepatic GR. We also hypothesized that a single bout of endurance exercise would modify the GR cellular distribution under our DIO model. Male rats were either fed a standard (SD) or a HF diet for two weeks. Each group was subdivided into a non-exercised (Rest) and an acute exercised (EX) group. The HF diet resulted in a reduction of total hepatic GR (55%) and hepatic plasma membrane GR protein content (20%). These changes were accompanied by a significant increase in endosomal and lysosomal GR content with the feeding of a HF diet. The reduction of GR plasma membrane as well as the increase in endosomal GR was strongly correlated with an increase of PKC-alpha, suggesting a role of PKC-alpha in GR desensitization. EX increased significantly PKC-alpha protein content in both diets, suggesting a role of PKC-alpha in EX-induced GR desensitization. The present results suggest that liver lipid infiltration plays a role in reducing glucagon action in the liver through a reduction in total cellular and plasma membrane GR content. Furthermore, the GR desensitization observed in our in vivo model of HF diet-induced hepatic steatosis and in EX individuals may be regulated by PKC-alpha.
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PMID:High-fat diet-induced hepatic steatosis reduces glucagon receptor content in rat hepatocytes: potential interaction with acute exercise. 1705 32

Although steatohepatitis can be induced by an excessive intake of alcohol, it can also arise through various other causes, in which case it is known as non-alcoholic fatty liver disease (NAFLD). NAFLD is classified into two categories:simple fatty liver with a favorable clinical outcome, and non-alcoholic steatohepatitis (NASH), which is intractable and progressive. Recently in Japan, there has been an increase in the number of individuals at risk of lifestyle-related diseases, due to increased insulin resistance and visceral fat obesity. The metabolic syndrome (MS) is associated with several risk factors for atherosclerosis, including diabetes mellitus (DM), hypertension, and hyperlipidemia. Visceral fat obesity is the prime cause of NASH in the liver, and is therefore considered to be one of the phenotypic features of MS. Furthermore, most chronic liver diseases are associated with hepatitis C virus (HCV) infection. Fatty degeneration of hepatocytes is often observed in the liver of HCV-infected individuals, and results from viral suppression of mitochondrial beta-oxidation of fatty acid. The natural outcome of HCV infection is worse in patients with lifestyle-related high insulin resistance and visceral fat obesity. In this review, we describe the recent advances in research on progressive liver diseases that are the result of fat accumulation in the liver, with special reference to MS.
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PMID:1. Fatty liver and non-alcoholic steatohepatitis. 1722 Jun 9


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