Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resistin, an adipose-derived polypeptide hormone, is proposed as a candidate of insulin resistance, although its roles in inhibiting adipogenesis and in inflammation have also been suggested. Liver cirrhosis is characterized by elevated circulating proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), hyperinsulinemia and insulin resistance. The study aimed to examine resistin expression and its association with insulin and TNF-alpha in a cirrhotic rat model using bile duct ligation (BDL). The BDL-induced cirrhotic rats showed significantly lower fat mass, insulin sensitivity and elevated plasma insulin and TNF-alpha compared to sham animals. In addition, epididymal TNF-alpha and resistin mRNA and protein levels were higher in cirrhotic rats. In normal control rats, in vivo insulin infusion and ex vivo administration of TNF-alpha to cultured fat pads increased resistin gene expression significantly. These results implied that hyperinsulinemia and increased TNF-alpha levels might upregulate adipose resistin gene in BDL-induced liver cirrhosis. Further study is necessary to document the role of resistin in metabolic abnormalities of liver cirrhosis.
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PMID:Stimulated resistin expression in white adipose of rats with bile duct ligation-induced liver cirrhosis: relationship to cirrhotic hyperinsulinemia and increased tumor necrosis factor-alpha. 1573 63

Transdifferentiation of hepatic stellate cells (HSC) constitutes a major cellular event in the genesis of alcoholic liver fibrosis and cirrhosis and molecular mechanisms underlying this process is incompletely understood. Our laboratory proposed several years ago that HSC quiescence requires the transcriptional program known to be integral to preadipocyte to adipocyte differentiation. In support of the hypothesis, our research demonstrates the expression of adipogenic transcription factors (C/EBPs, PPARgamma, SREBP-1c, LXRalpha) and adipocyte-specific genes (adipsin, resistin) are high in quiescent HSC and depleted in activated HSC. Three gain-of-function approaches have been taken to test this notion: the treatment of activated HSC with the adipocyte differentiation cocktail; ectopic expression of PPARgamma or SREBP-1c. All three treatments coordinately upregulate a panel of putative adipogenic transcription factors and cause morphologic and biochemical reversal of activated HSC to quiescent cells. These findings establish a new conceptual framework for the treatment of liver fibrosis and propose an intriguing notion concerning the plasticity of HSC.
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PMID:Adipogenic phenotype of hepatic stellate cells. 1634 97

The adipokine resistin has been implicated in obesity and insulin resistance. Liver cirrhosis is associated with decreased body fat mass and insulin resistance. We determined plasma resistin levels in 57 patients with cirrhosis, 13 after liver transplantation, and 30 controls and correlated these with hemodynamic as well as hepatic and systemic metabolic parameters. Patients with cirrhosis had, dependent on the clinical stage, an overall 86% increase in resistin levels (P < 0.001) with hepatic venous resistin being higher than arterial levels (P < 0.001). Circulating resistin was significantly correlated with plasma TNF-alpha levels (r = 0.62, P < 0.001). No correlation was observed between resistin and hepatic hemodynamics, body fat mass, systemic energy metabolism, and the degree of insulin resistance. However, plasma resistin in cirrhosis was negatively associated with hepatic glucose production (r = -0.47, P < 0.01) and positively with circulating free fatty acids (FFA; r = 0.40, P < 0.01) and ketone bodies (r = 0.48, P < 0.001) as well as hepatic ketone body production (r = 0.40, P < 0.01). After liver transplantation, plasma resistin levels remained unchanged, whereas insulin resistance was significantly improved (P < 0.01). These data provide novel insights into the role of resistin in the pathophysiological background of a catabolic disease in humans and also indicate that resistin inhibition may not represent a suitable therapeutic strategy for the treatment of insulin resistance and diabetes in patients with liver cirrhosis.
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PMID:Elevated resistin levels in cirrhosis are associated with the proinflammatory state and altered hepatic glucose metabolism but not with insulin resistance. 1647 79

Liver fibrosis is a dynamic process consisting of the chronic activation of the wound healing reaction in response to reiterated liver damage, leading to the excessive deposition of fibrillar extracellular matrix into the liver and eventually, if the cause of injury is not removed, to liver cirrhosis. The term "adipokines" identifies a group of polypeptide molecules secreted primarily by adipose tissue, which exert local, peripheral and/or central actions. Additionally to their well-established role in controlling adipose tissue physiology, adipokines have been shown to be involved in different obesity-related diseases, such as hypertension, atherosclerosis and type 2 diabetes. Accumulating data demonstrate that obesity and insulin resistance are associated with a more severe and faster progression of the fibrogenic process in different chronic liver diseases. Therefore, numerous recent studies have analyzed the role played by adipokines in the hepatic wound healing process, identifying novel roles as modulators of liver pathophysiology. This review summarizes the more significant and recent findings concerning the role played by adipocyte-derived molecules, such as leptin, adiponectin and resistin, in the liver fibrogenic process. The actions of different adipokines on the biology of liver resident cells, as well as their effects in different animal models of liver injury are discussed. The variations in the circulating levels and in the intrahepatic expression of these molecules occurring in patients with different chronic liver diseases will be also analyzed.
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PMID:The role of adipokines in liver fibrosis. 1860 1

No detailed data are available on hepatic clearance, postprandial release, and distribution profile of metabolically active adipokines in splanchnic blood compartments such as portal and hepatic veins. This would be a prerequisite for understanding the role of visceral adipose tissue-derived adipokines in metabolism. Adiponectin, resistin, leptin, and visfatin concentrations were measured by enzyme-linked immunosorbent assay in peripheral veins, arterial blood, hepatic veins, and portal veins in 50 patients with liver cirrhosis undergoing transjugular intrahepatic portosystemic shunt implantation, in 6 patients with normal liver function, and in fasted and fed rats. Adiponectin, leptin, resistin, and visfatin did not differ among blood compartments in normal-weight probands in the fasted state. Adiponectin and leptin levels were similar in patients with and without liver cirrhosis. Systemic visfatin levels were decreased and resistin levels were increased in liver cirrhosis. Visfatin secretion was higher from visceral than from peripheral subcutaneous adipose tissue in liver cirrhosis. There was no hepatic clearance of visfatin. Leptin secretion was higher from peripheral than from visceral adipose tissue. Leptin did not undergo hepatic clearance. Resistin and adiponectin did not differ between blood compartments in liver cirrhosis. Resistin concentrations increased upon feeding in rats, and there was an increase in the postprandial clearance of adiponectin by the liver. A postprandial increase of leptin concentrations was restricted to peripheral adipose tissue in rats. The results give insight into the dynamics of splanchnic adipokine concentrations and help critically interpret data derived from messenger RNA expression studies.
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PMID:Splanchnic concentrations and postprandial release of visceral adipokines. 1991 46

Nonalcoholic steatohepatitis (NASH) represents one of the most common liver diseases. It is strongly associated with obesity and insulin resistance and is thought to be part of the metabolic syndrome. NASH can progress to cirrhosis and liver failure. Adipohormones, synthesized in adipose tissue, are involved in the pathophysiology of many acute and chronic liver diseases. The aim of this study was to evaluate the plasma concentrations of adiponectin, resistin, leptin, TNF-alpha and Il-6 in patients with NASH, as well as their correlation with the pathologic parameters. Serum concentration of leptin, adiponectin, resistin, insulin, TNF-alpha, IL-6 were measured with ELISA method. Liver biopsies were obtained from 18 (age 42.55+/-21 years) patients. NASH has been classified according to Dixon score. The control group was represented by 16 non-obese subjects. Mean serum concentration of adiponectin in patients with NASH was significantly lower than in healthy subjects (4.87+/-1.96 vs. 8.33+/-4.56 ng/ml; p<0.05). Mean serum levels of TNF-alpha in patients with NASH were significantly higher than in controls (34.2+/-19.7 vs. 20.7+/-15.5 ng/ml; p<0.05). In patients with more advanced inflammation (grade 2-3) and fibrosis (stage 2) in pathology, serum concentration of leptin was significantly higher than in patients with steatosis and less advanced inflammation (grade 1) and fibrosis (stage 1) (median 8.94 vs. 16.2 ng/ml; p<0.05). No significant differences of serum concentration of others adipohormones between these two groups of patients were stated. Moreover, we observed the correlation in serum levels (examined group vs controls) between: resistin and TNF-alpha (r = 0.62; p<0.05), adiponectin and IL-6 (r = -0.60; p<0.05) and leptin and insulin (r = -0.51; p<0.05). In conclusion, based on our study we speculate that changes of adipohormones levels may be markers of NASH and the serum level of leptin can be associated with more advanced form of NASH.
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PMID:Adipohormones as prognostric markers in patients with nonalcoholic steatohepatitis (NASH). 1999 85

Adipose tissue dysfunction, featured by insulin resistance and/or dysregulated adipokine production, plays a central role not only in disease initiation but also in the progression to nonalcoholic steatohepatitis and cirrhosis. Promising beneficial effects of betaine supplementation on nonalcoholic fatty liver disease (NAFLD) have been reported in both clinical investigations and experimental studies; however, data related to betaine therapy in NAFLD are still limited. In this study, we examined the effects of betaine supplementation on hepatic fat accumulation and injury in mice fed a high-fat diet and evaluated mechanisms underlying its hepatoprotective effects. Male C57BL/6 mice weighing 25 +/- 0.5 (SE) g were divided into four groups (8 mice/group) and started on one of four treatments: control diet, control diet supplemented with betaine, high-fat diet, and high-fat diet supplemented with betaine. Betaine was supplemented in the drinking water at a concentration of 1% (wt/vol) (anhydrous). Our results showed that long-term high-fat feeding caused NAFLD in mice, which was manifested by excessive neutral fat accumulation in the liver and elevated plasma alanine aminotransferase levels. Betaine supplementation alleviated hepatic pathological changes, which were concomitant with attenuated insulin resistance as shown by improved homeostasis model assessment of basal insulin resistance values and glucose tolerance test, and corrected abnormal adipokine (adiponectin, resistin, and leptin) productions. Specifically, betaine supplementation enhanced insulin sensitivity in adipose tissue as shown by improved extracellular signal-regulated kinases 1/2 and protein kinase B activations. In adipocytes freshly isolated from mice fed a high-fat diet, pretreatment of betaine enhanced the insulin signaling pathway and improved adipokine productions. Further investigation using whole liver tissues revealed that betaine supplementation alleviated the high-fat diet-induced endoplasmic reticulum stress response in adipose tissue as shown by attenuated glucose-regulated protein 78/C/EBP homologous protein (CHOP) protein abundance and c-Jun NH(2)-terminal kinase activation. Our findings suggest that betaine might serve as a safe and efficacious therapeutic tool for NAFLD by improving adipose tissue function.
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PMID:Betaine improved adipose tissue function in mice fed a high-fat diet: a mechanism for hepatoprotective effect of betaine in nonalcoholic fatty liver disease. 2020 61

Nonalcoholic fatty liver disease (NAFLD) develops in 17-33% of the population of developed countries. The incidence of NAFLD is constantly growing due to the increasing prevalence of obesity. It is estimated that one third of subjects with NAFLD suffer from nonalcoholic steatohepatitis (NASH) and 15% of them develop liver cirrhosis within a five-year period. In recent years this important complication of obesity became the subject of numerous studies. It, the pathogenesis of NAFLD is still unclear. A key role in the development of this disease was attributed to insulin resistance. Hormones and cytokines produced by adipose tissue called adipokines may be a link between obesity, insulin resistance, and NAFLD. However, it is well known that increased levels of adipokines such as TNF-alpha, IL-6, and resistin and a decreased level of adiponectin augment inflammation in the liver. Further studies are necessary to explain the roles of leptin, visfatin, retinol binding protein-4, omentin, and vaspin in the pathogenesis of NAFLD. The aim this paper is to introduce new areas of study on the pathogenesis of NAFLD.
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PMID:[The role of adipokines and insulin resistance in the pathogenesis of nonalcoholic fatty liver disease]. 2049 98

The presence of autoantibodies against C-reactive protein (anti-CRP) has been reported in association with autoimmunity and histopathology in chronic hepatitis C virus (HCV) infection. Resistin could play a role in the pathogenesis of hepatitis, although results on HCV infection are ambiguous. Here we retrospectively analyzed anti-CRP and resistin levels in the sera of 38 untreated and well-characterized HCV patients at the time of their first liver biopsy. HCV activity and general health were assessed by a physician at least yearly until follow-up ended. Anti-CRP and resistin were also measured in patients with autoimmune hepatitis (AIH) and nonalcoholic fatty liver disease (NAFLD). Anti-CRP antibodies were registered in all HCV patients, whereas only a few AIH (11%) and NAFLD (12%) sera were positive. Anti-CRP levels were related to histopathological severity and were highest in patients with cirrhosis at baseline. Resistin levels were similar in HCV, AIH, and NAFLD patients, but high levels of resistin were associated with early mortality in HCV patients. Neither anti-CRP nor resistin predicted a response to interferon-based therapy or cirrhosis development or was associated with liver-related mortality. We conclude that anti-CRP antibodies are frequently observed in chronic HCV infection and could be a useful marker of advanced fibrosis and portal inflammation.
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PMID:High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation. 2233 91

Obesity is rapidly becoming pandemic and is associated with increased carcinogenesis, especially hepatocellular carcinoma (HCC). Adipose tissue is considered as an endocrine organ because of its capacity to secrete a variety of adipokines, such as leptin, adiponectin and resistin. Recently, adipokines have been demonstrated to be associated with kinds of chronic liver diseases including fibrosis, cirrhosis and carcinogenesis. Direct evidence is accumulating rapidly supporting the inhibitory and/or activating role of adipokines in the process of carcinogenesis and progression of human HCC. This review aims to provide important insight into the potential mechanisms of adipokines in the development of HCC.
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PMID:Obesity, adipokines and hepatocellular carcinoma. 2340 22


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