Coordinated regulation of scopoletin at adipose tissue–liver axis improved alcohol-induced lipid dysmetabolism and inflammation in rats

• Scopoletin attenuated alcohol-induced lipid dysmetabolism and inflammation in rats.
• Scopoletin coordinated lipid metabolism and inflammation at adipose tissue and liver.
• Scopoletin up-regulated circulating adiponectin level and AdipoR2-AMPK pathway.
• Scopoletin down-regulated inflammatory response via inhibition of TLR4 pathway.

There is increasing evidence that alcohol-induced white adipose tissue (WAT) dysfunction contributes to disturbance of hepatic lipid metabolism. This study investigated the effects of scopoletin on lipid homeostasis and inflammation at the WAT and liver in chronic alcohol-fed rats. Rats were fed a liquid diet containing 5% alcohol with or without two doses of scopoletin (0.001% and 0.005%) for 8 weeks. Scopoletin decreased serum triglyceride and cytokines (TNFα and IL-6) levels and hepatic and WAT lipid levels, whereas it increased WAT adiponectin mRNA and serum adiponectin levels, up-regulated hepatic gene and protein expression of AdipoR2 and activated AMPK. Additionally, scopoletin inhibited the expression of lipogenic genes (SREBP-1c and Fasn) and increased the expression of fatty acid oxidative genes (PPARα, Acsl1, CPT, Acox, and Acaa1a) in both WAT and liver. Alcohol led to significant up-regulation of WAT lipolysis and hepatic Cidea gene expression, whereas it decreased the WAT Cidea gene level; however, scopoletin reversed these changes. Scopoletin significantly down-regulated TLR4 signaling genes such as MyD88, TRIF, NFκB, TNFα and IL-6 in WAT and liver. These results indicated that coordinated regulation of scopoletin at the WAT–liver axis may play an important role in improvement of alcohol-induced lipid dysregulation and inflammation.

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