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

Non-alcoholic fatty liver disease (NAFLD) is now recognized as one of the most important causes of chronic liver disease in Western Countries, and is the hepatic manifestation of metabolic syndrome. The prevalence of NAFLD has increased with the global epidemic of obesity and type 2 diabetes mellitus. The pathophysiological hallmark of NAFLD is insulin resistance, associated with mediators of oxidative stress and inflammatory cytokines. Although simple steatosis by itself is generally benign, patients with histologically proven non-alcoholic steatohepatitis (NASH) can progress to cirrhosis. Hepatitis C (HCV) is another common cause of liver disease with some potential for progression to cirrhosis. Steatosis is present in almost 50% of patients infected by HCV. Hepatic steatosis in the setting of another liver disease (such as HCV) is associated liver disease progression. In particular, significant fibrosis is observed in patients with HCV whose liver biopsies show significant steatosis or superimposed NASH. This article reviews the host and viral factors potentially involved in the interaction between NAFLD and HCV. These factors include mediators of metabolic syndrome such as adipokines, inflammatory cytokines, factors associated with oxidative stress, lipid peroxidation products, as well as apoptosis and hepatic stellate cell activation with the resultant deposition of extracellular matrix. In addition to the mediators of metabolic syndrome (host factors), hepatic steatosis can be influenced by viral factors. The most important viral factor is HCV genotype 3, which has been independently associated with hepatic steatosis. Finally, superimposed NAFLD and visceral fat are associated with lower response rates to antiviral therapy in non-genotype 3 patients. Furthermore, viral clearance is associated with the resolution of hepatic steatosis in HCV genotype 3 but not other HCV genotypes. In these genotypes, hepatic steatosis and its impact on response to therapy are related to metabolic syndrome. Thus, the management of obesity and metabolic syndrome in patients with chronic hepatitis C may be important for reducing the risk of progression as well as improving the efficacy of antiviral therapy.
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PMID:Non-alcoholic fatty liver disease and hepatitis C infection. 1655 85

The clinical impact of nonalcoholic fatty liver disease depends on its prevalence and natural history. The prevalence in the adult population is estimated to be about 23% and is on the increase. Thus, it has become the most common cause of persistent elevated liver enzymes, chronic liver disease, and cryptogenic cirrhosis in developed countries. The increasing prevalence of nonalcoholic fatty liver disease, which is approaching epidemic proportions, is parallel to that of other disorders associated with insulin resistance, especially obesity and type 2 diabetes mellitus. This entity occurs in men and women equally and in all age groups. The natural history is poorly defined mainly due to the scarcity of histologic follow-up studies. Although steatosis alone has a more benign clinical course, steatohepatitis is a progressive fibrotic disease, in which cirrhosis and liver-related death occur in a similar way to other causes of chronic liver diseases. Progression seems to be mainly dependent on the severity of histological damage at diagnosis, but age older than 40 years, obesity, and type 2 diabetes have also been associated with an increased risk of liver fibrosis and progression to cirrhosis.
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PMID:[Epidemiology and natural history of primary nonalcoholic fatty liver disease]. 1658 96

Alstrom syndrome is a rare autosomal recessive disorder characterized by retinal degeneration, sensorineural hearing loss, obesity, type 2 diabetes mellitus and chronic nephropathy. It may be associated with acanthosis nigricans, hypergonadotropic hypogonadism, hepatic dysfunction, hepatic steatosis, hyperlipidaemia, dilated cardiomyopathy and short stature. We report a patient with Alstrom syndrome who had hypergonadotropic hypogonadism, hepatic dysfunction, hepatic steatosis and short stature with normal body weight, all of which are seen infrequently with this syndrome.
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PMID:Rare case of Alstrom syndrome without obesity and with short stature, diagnosed in adulthood. 1666 65

Fatty liver and hepatic triglyceride accumulation are strongly associated with obesity, insulin resistance and type 2 diabetes, and are subject to nutritional influences. Hepatic regulation of glucose and lipid homeostasis is influenced by a complex system of hormones, hormonally regulated signalling pathways and transcription factors. Recently, considerable progress has been made in elucidating molecular pathways and potential factors that are affected in insulin-resistant states. In this review we discuss some of the key factors that are involved in both the regulation of glucose and lipid metabolism in the liver. Understanding the molecular network that links hepatic lipid accumulation and impaired glucose metabolism may provide targets for dietary or pharmacological interventions.
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PMID:Signalling mechanisms linking hepatic glucose and lipid metabolism. 1714 88

Lack of adipose tissue, either complete or partial, is the hallmark of disorders known as lipodystrophies. Patients with lipodystrophies suffer from metabolic complications similar to those associated with obesity, including insulin resistance, type 2 diabetes, hypertriglyceridemia, and hepatic steatosis. The loss of body fat in inherited lipodystrophies can be caused by defects in the development and/or differentiation of adipose tissue as a consequence of mutations in a number of genes, including PPARG (encoding a nuclear hormone receptor), AGPAT2 (encoding an enzyme involved in the biosynthesis of triglyceride and phospholipids), AKT2 (encoding a protein involved in insulin signal transduction), and BSCL2 (encoding seipin, whose role in the adipocyte biology remains unclear). The loss of body fat can also be caused by the premature death of adipocytes due to mutations in lamin A/C, nuclear lamina proteins, and ZMPSTE24, which modifies the prelamin A post-translationally. In this review, we focus on the molecular basis of inherited lipodystrophies as they relate to adipocyte biology and their associated phenotypic manifestations.
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PMID:Genetic disorders of adipose tissue development, differentiation, and death. 1672 6

Adiponectin is a fat cell-secreted hormone with antidiabetic and anti-inflammatory activities. The reduced adiponectin levels are associated with obesity-related metabolic syndrome. Replenishment of this hormone into animal models can improve insulin sensitivity, decrease blood glucose and lipid levels, and prevent the development of atherosclerosis and fatty liver injury. Despite these findings, the underlying molecular mechanisms remain largely unknown. Here, we have used affinity chromatography to purify the protein complexes that are associated with adiponectin in human serum. The nature of these adiponectin-binding proteins was analyzed by MS/MS. Eight proteins from the adiponectin-containing protein mixtures have been identified. Many of them, including thrombospondin-1 (TSP-1), histidine-rich glycoprotein, kininogen 1, and alpha 2 macroglobulin (alpha2M), are well-known glycoproteins involved in the regulation of inflammation, angiogenesis, and tissue remodeling. Coimmunoprecipitation and radioligand competitive-binding assays confirmed the direct interactions between adiponectin and alpha2M, or TSP-1. Moreover, these specific bindings were also detected in the serum samples derived from both healthy human subjects and patients with type 2 diabetes. In summary, our study demonstrated that, in the circulation, adiponectin forms protein complexes with other serum proteins. These proteins might serve as the physiological-binding partners of adiponectin and regulate its bioavailability and biological activities.
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PMID:Proteomic characterization of human serum proteins associated with the fat-derived hormone adiponectin. 1676 90

In Japan, much attention has been paid to NASH and NAFLD for the past several years and the prevalence of this disease entity has been estimated, and NASH is thought to be present in 10% of those who have fatty liver diseases. Other points out the prevalence of NASH in Japan as 6 to 8 hundred thousand patients. The last two or three decades have seen the evolution of Western-style life of near complete inactivity, energy-dense food choices and liberal fiscal resources to obtain them and other means to avoid physical activity. Moreover, what is increasingly apparent is that NASH and NAFLD is not a Western disease and many population groups in the Asia-Pacific region are particularly prone to type 2 diabetes. Thus, it is not surprising that NASH has increasingly been diagnosed in several regions in Asia including Indonesia, Malaysia, Philippines, Thailand and India.
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PMID:[Current trends of NASH/NAFLD in Asia-Pacific region]. 1676 3

In the last 15 years evidence has been accumulating suggesting that hepatic steatosis may be the starting point for a progressive liver disease. Nonalcoholic steatosis (nonalcoholic fatty liver disease, NAFLD) is now considered a metabolic pathway to advanced liver disease, cirrhosis and hepatocellular carcinoma. Liver disease of other etiology, namely hepatitis C virus, may interact with NAFLD, although the underlying mechanism(s) have not been fully elucidated. Type 2 diabetes mellitus, obesity and dyslipidemia are the principal factors associated with NAFLD, which is now considered the hepatic expression of metabolic syndrome (MS). Several studies have dealt with the relationship of NAFLD and MS, the risk of liver disease associated with the classical features of MS, the importance of insulin resistance as the common soil of different diseases. We still need to clarify the mechanism(s) responsible for liver disease progression from pure fatty liver, to steatohepatitis and to cirrhosis, and the reason(s) why only a few NAFLD cases progress to terminal liver failure while others (the majority) will have a cardiovascular outcome. The epidemics of obesity and diabetes of Western countries is expected to produce a significant increase of metabolic liver disease in the next years. Prevention and intervention programs based on lifestyle are therefore mandatory to reduce the burden of metabolic liver disease.
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PMID:Nonalcoholic fatty liver disease and the metabolic syndrome. 1677 54

Fatty acid-binding proteins (FABPs) are cytosolic fatty acid chaperones that play a critical role in systemic regulation of lipid and glucose metabolism. In animals lacking the adipocyte/macrophage FABP isoforms aP2 and mal1, there is strong protection against diet-induced obesity, insulin resistance, type 2 diabetes, fatty liver disease, and hypercholesterolemic atherosclerosis. On high-fat diet, FABP-deficient mice also exhibit enhanced muscle AMP-activated kinase (AMPK) and reduced liver stearoyl-CoA desaturase-1 (SCD-1) activities. Here, we performed a cross between aP2(-/-), mal1(-/-), and leptin-deficient (ob/ob) mice to elucidate the role of leptin action on the metabolic phenotype of aP2-mal1 deficiency. The extent of obesity in the ob/ob-aP2-mal1(-/-) mice was comparable with ob/ob mice. However, despite severe obesity, ob/ob-aP2-mal1(-/-) mice remained euglycemic and demonstrated improved peripheral insulin sensitivity. There was also a striking protection from liver fatty infiltration in the ob/ob-aP2-mal1(-/-) mice with strong suppression of SCD-1 activity. On the other hand, the enhanced muscle AMPK activity in aP2-mal1(-/-) mice was lost in the ob/ob background. These results indicated that both decreased body weight and enhanced muscle AMPK activity in aP2-mal1(-/-) mice are potentially leptin dependent but improved systemic insulin sensitivity and protection from liver fatty infiltration are largely unrelated to leptin action and that insulin-sensitizing effects of FABP deficiency are, at least in part, independent of its effects on total-body adiposity.
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PMID:Regulation of metabolic responses by adipocyte/macrophage Fatty Acid-binding proteins in leptin-deficient mice. 1680 58

For a long time, hepatic steatosis was believed to be a benign condition. Only recently, liver steatosis, also termed non-alcoholic fatty liver disease (NAFLD), has gained much interest. In most cases of NAFLD, a condition regarded as the hepatic component of the metabolic syndrome, the enzyme alanine aminotransferase (ALT) is elevated and consequently has been used as a marker for NAFLD. More recently, several cross-sectional and prospective studies have demonstrated associations of this liver enzyme with features of the metabolic syndrome and type 2 diabetes mellitus. This review discusses the biochemical and metabolic properties of ALT, its applicability as a marker of NAFLD and describes its possible role in the pathogenesis of the metabolic syndrome and type 2 diabetes mellitus and subsequent cardiovascular disease. In addition, treatment strategies to ameliorate NAFLD and the associated risks are discussed.
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PMID:Alanine aminotransferase as a marker of non-alcoholic fatty liver disease in relation to type 2 diabetes mellitus and cardiovascular disease. 1682 76


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