Moderate alcohol consumption alters hepatic AdipoR1/SREBP‐1c and SIRT1 activity in rats with pre‐existing NASH

This study investigated whether the detrimental effect of moderate alcohol intake is due to alterations of adiponectin/Adiponectin receptor (AdipoR)/Sirtuin 1 (SIRT1)‐related signaling and lipid metabolism in the livers. Rats were fed with a high‐fat diet (HFD, 71% total energy (TE) from fat) for 6 weeks to induce NASH, and then divided into two sub‐groups: fed either a modified high‐fat diet (HFD, 55% TE from fat and 16% TE from dextrin) or a modified high‐fat alcoholic diet (HFA, 55% TE from fat and 16% TE from ethanol), for additional 4 weeks. We found that, in comparison to HFD group: 1) plasma adiponectin was lower in the HFA group although this change reached a statistical tendency (p=0.06); 2) HFA significantly decreased hepatic AdipoR1 but not AdipoR2; and 3) hepatic FAS mRNA and SREBP‐1c protein levels were significantly up‐regulated, while both DGAT1/2 and CPT‐I mRNA expressions were down‐regulated in HFA. Interestingly, HFA increased hepatic SIRT1 protein levels but significantly decreased SIRT1 activity. In conclusion, the data suggest that the down‐regulation of Adiponectin/AdipoR‐related signaling and SIRT1 activity contribute to the alcohol intake‐exacerbated liver injuries in rats with pre‐existing NASH. (Supported by USDS/ARS:1950–51000‐064S; FAPESP:2011/21664–9)