Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice

Abstract

The protective effect of dietary saturated fatty acids against the development of alcoholic liver disease has long been known, but the underlying mechanism is not completely understood. We examined the involvement of the adipocyte hormone adiponectin. Circulating adiponectin levels were significantly elevated by chronic ethanol administration to mice consuming a diet high in saturated fat. The increase in circulating adiponectin was associated with the activation a set of hepatic signaling pathways mediated through AMP-activated protein kinase, PPAR-␣, and PPAR-␥ coactivator ␣, which in turn led to markedly increased rates of fatty acid oxidation, prevention of hepatic steatosis, and alleviation of liver enzyme changes. Furthermore, treatment of rat 3T3-L1 adipocytes with saturated fatty acids (palmitic or stearic acids) in the presence of ethanol increased secretion of adiponectin and enhanced activity of a mouse adiponectin promoter. In conclusion, the protective action of saturated fat against the development of alcoholic fatty liver in mice is partially mediated through induction of adiponectin. The present findings suggest a novel paradigm for dietary fatty acids in the pathogenesis of alcoholic liver disease and provide a promising therapeutic strategy-nutritional modulation of adiponectin-in treating human alcoholic fatty liver disease. (HEPATOLOGY 2005;42:568 -577.)

Plasma Adipokines and Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Virus–Infected Carriers: A Prospective Study in Taiwan

“…Studies from animals and humans indicate that circulating adiponectin had some hepatoprotective effects on various stages of liver injuries, and most of them were found in NAFLD (38,39). It has been demonstrated that the increase of circulating adiponectin was associated with the activation of AMP-activated protein kinase, PPAR-a and PGC1-a, which in turn led to markedly increased rates of fatty acid oxidation, thus preventing hepatic steatosis and alleviating liver enzyme elevation (40)(41)(42)(43). It is well known that obesity and insulin resistance are two common causes shared by low plasma adiponectin and hepatic steatosis, the initiating hit of NAFLDs (44).…”

S‐Adenosylmethionine Attenuates Hepatic Lipid Synthesis in Micropigs Fed Ethanol With a Folate‐Deficient Diet

“…Low circulating adiponectin levels were associated with hepatic steatosis, whereas the administration of adiponectin promoted hepatic lipid oxidation and reduced lipid synthesis in ethanol-fed mice (Xu et al, 2003). Hepatic steatosis in ethanol-fed mice was prevented by increasing saturated fat in the diet, in association with increased circulating adiponectin, hepatic AMPK activation, and lipid oxidation (You et al, 2005). Activated AMPK stimulates fatty acid oxidation at the same time as decreasing the stability of mature nSREBP-1c, thus reducing the expression of lipogenic genes including ACC, FAS, and glycerol-3-phosphate acyltransferase (GPAT) (Tomita et al, 2005;Zhou et al, 2001).…”

The role of fatty acids in the development and progression of nonalcoholic fatty liver disease

“…Saturated fats have also been shown to reduce proinflammatory mediators, including TNF-α, cyclooxygenase-2 and NFκB [92,93]. It has also been suggested that dietary saturated fat alleviates ALFD, in part, via upregulation of adiponectin expression and production in adipose tissue [97]. These changes in adiponectin, in turn, may contribute to the enhancement of fatty acid oxidation and thus reduced steatosis.…”