IJMS, Vol. 20, Pages 6282: Resveratrol Treatment Enhances the Cellular Response to Leptin by Increasing OBRb Content in Palmitate-Induced Steatotic HepG2 Cells (International Journal of Molecular Sciences)

The interaction of leptin with its hepatic longest receptor (OBRb) promotes thephosphorylation of signal transducer and activator of transcription-3 (STAT3), protecting the liverfrom lipid accumulation. However, leptin signalling is disrupted in hepatic steatosis, causing leptinresistance. One promising strategy to combat this problem is the use of bioactive compounds suchas polyphenols. Since resveratrol (RSV) is a modulator of lipid homeostasis in the liver, weinvestigated whether treatment with different doses of RSV restores appropriate leptin action andfat accumulation in palmitate-induced steatotic human hepatoma (HepG2) cells. Both RSVmetabolism and the expression of molecules implicated in leptin signalling were analysed. RSV ata 10 μM concentration was entirely metabolized to resveratrol-3-sulfate after 24 and counteractedleptin resistance by increasing the protein levels of OBRb. In addition, RSV downregulated theexpression of lipogenic genes including fatty acid synthase (Fas) and stearoyl-CoA desaturase-1 (Scd1)without any significant change in Sirtuin-1 (SIRT1) enzymatic activity. These results demonstratethat RSV restored leptin sensitivity in a cellular model of hepatic steatosis in a SIRT1-independentmanner.