Mechanisms of disease: adipocytokines and visceral adipose tissue--emerging role in nonalcoholic fatty liver disease.
There is increasing evidence that visceral adipose tissue is a causative risk factor for fatty liver and nonalcoholic steatohepatitis. Adipose tissue-derived secretory proteins are collectively named adipocytokines. Obesity and mainly visceral fat accumulation impair adipocyte function and adipocytokine secretion and the altered release of these proteins contributes to hypertension, impaired fibrinolysis and insulin resistance. This review summarizes recent findings on the role of the adipocytokines adiponectin, leptin and resistin in the context of hepatic insulin resistance, fatty liver and liver fibrosis. Elevated levels of resistin antagonize hepatic insulin action and raise plasma glucose levels. Leptin exerts insulin-sensitizing effects, but obesity has been linked to leptin resistance and low levels of circulating leptin receptor, indicating that high levels of leptin cannot mediate its beneficial effects. Adiponectin improves insulin sensitivity; however, low circulating adiponectin is found in the obese state. Adiponectin is an anti-inflammatory protein, whereas leptin augments inflammation and fibrogenesis. Disturbed adipocytokine secretion might, therefore, promote hepatic steatosis and the development of nonalcoholic steatohepatitis. The beneficial effects of the therapeutic approaches so far tested in the treatment of fatty liver disease and fibrosis might be due to the modulation of these adipocytokines.
Schäffler
Andreas
A
Department of Internal Medicine I, University of Regensburg, Germany.
Schölmerich
Jürgen
J
Büchler
Christa
C
D017667:Adipocytes / Q000276:immunology / Q000378:metabolism*; D000273:Adipose Tissue / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology*; D005234:Fatty Liver / Q000276:immunology* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000276:immunology; D020738:Leptin / Q000276:immunology; D008103:Liver Cirrhosis / Q000276:immunology / Q000503:physiopathology; D009765:Obesity / Q000276:immunology; D014781:Viscera / Q000276:immunology
D016207:Cytokines; D007328:Insulin; D020738:Leptin; D005947:Glucose