Resveratrol promotes hepatic lipid decomposition by regulating ATGL/CGI58 and Rab7/LC3β through perilipin 2

Objective To investigate the effect of resveratrol (RSV) on enhancing hepatic lipolysis and lipophagy through perilipin 2 (PLIN2), and elucidate its underlying mechanism. Methods Human liver cell line HHL-5 was used to establish a cellular model of steatosis, and then the cells were divided into control group, palmitic acid (PA, model) group, siPLIN2 transfection group and RSV treatment groups (5, 10, 20, 40 μmol/L). CCK-8 assay, intracellular TG detection and Bodipy staining were adopted to detect the effects of different concentrations of RSV on cell viability and lipid degradation of the model cells. The expression of hepatic lipid decomposition related molecules and the changes of their average fluorescence intensity were determined by real-time qPCR, Western blotting and immunofluorescence staining, respectively. In addition, PLIN2 siRNA transfection technology was performed to verify the pathway of RSV promoting hepatic lipid decomposition. Results As compared with the control group, the intracellular TG content and the average fluorescence intensity of lipid droplets were notably increased in the PA group (P < 0.05), while the expression of hepatic lipolysis and lipophagy related molecules including PLIN2, ATGL, CGI58, Rab7, and LC3β were significantly decreased, with their mean fluorescence intensity and co-localization were declined as well (P < 0.05). After the treatment of 40 μmol/L RSV, the lipid accumulation of steatosis HHL-5 cells was reduced (P < 0.05), whereas the expression of lipolysis and lipophagy related molecules, their average fluorescence intensity and co-localization were elevated (P < 0.05). However, the knockdown of PLIN2 blocked RSV from regulating lipolysis and lipophagy related molecules and improving hepatocyte steatosis (P < 0.05). Conclusions RSV promotes the expression and interaction of ATGL/CGI58 and Rab7/LC3β through upregulating PLIN2, and thus enhances hepatic lipolysis and lipophagy.