Activation of peroxisome proliferator-activated receptor-gamma by rosiglitazone improves lipid homeostasis at the adipose tissue-liver axis in ethanol-fed mice

作者：Sun Xiuhua; Tang Yunan; Tan Xiaobing; Li Qiong; Zhong Wei; Sun Xinguo; Jia Wei; McClain Craig J; Zhou Zhanxiang^*

来源：American Journal of Physiology - Gastrointestinal and Liver Physiology, 2012, 302(5): G548-G557.

DOI：10.1152/ajpgi.00342.2011

• lipid storage disorder
• adipose lipid metabolism
• alcoholic fatty liver

Sun X, Tang Y, Tan X, Li Q, Zhong W, Sun X, Jia W, McClain CJ, Zhou Z. Activation of peroxisome proliferator-activated receptor-gamma by rosiglitazone improves lipid homeostasis at the adipose tissue-liver axis in ethanol-fed mice. Am J Physiol Gastrointest Liver Physiol 302: G548-G557, 2012. First published December 15, 2012; doi:10.1152/ajpgi.00342.2011.-The development of alcohol-induced fatty liver is associated with a reduction of white adipose tissue (WAT). Peroxisome proliferator-activated receptor (PPAR)-gamma prominently distributes in the WAT and plays a crucial role in maintaining adiposity. The present study investigated the effects of PPAR-gamma activation by rosiglitazone on lipid homeostasis at the adipose tissue-liver axis. Adult C57BL/6 male mice were pair fed liquid diet containing ethanol or isocaloric maltose dextrin for 8 wk with or without rosiglitazone supplementation to ethanol-fed mice for the last 3 wk. Ethanol exposure downregulated adipose PPAR-gamma gene and reduced the WAT mass in association with induction of inflammation, which was attenuated by rosiglitazone. Ethanol exposure stimulated lipolysis but reduced fatty acid uptake capacity in association with dysregulation of lipid metabolism genes. Rosiglitazone normalized adipose gene expression and corrected ethanol-induced lipid dyshomeostasis. Ethanol exposure induced steatosis and upregulated inflammatory genes in the liver, which were attenuated by rosiglitazone. Hepatic peroxisomal fatty acid beta-oxidation was suppressed by ethanol in associated with inhibition of acyl-coenzyme A oxidase 1. Rosiglitazone elevated plasma adiponectin level and normalized peroxisomal fatty acid beta-oxidation rate. However, rosiglitazone did not affect ethanol-reduced very low-density lipoprotein secretion from the liver. These results demonstrated that activation of PPAR-gamma by rosiglitazone reverses ethanol-induced adipose dysfunction and lipid dyshomeostasis at the WAT-liver axis, thereby abrogating alcoholic fatty liver.

• 出版日期2012-3