Abstract
The interaction of leptin with its hepatic longest receptor (OBRb) promotes the phosphorylation of signal transducer and activator of transcription-3 (STAT3), protecting the liver from lipid accumulation. However, leptin signalling is disrupted in hepatic steatosis, causing leptin resistance. One promising strategy to combat this problem is the use of bioactive compounds such as polyphenols. Since resveratrol (RSV) is a modulator of lipid homeostasis in the liver, we investigated whether treatment with different doses of RSV restores appropriate leptin action and fat accumulation in palmitate-induced steatotic human hepatoma (HepG2) cells. Both RSV metabolism and the expression of molecules implicated in leptin signalling were analysed. RSV at a 10 μM concentration was entirely metabolized to resveratrol-3-sulfate after 24 and counteracted leptin resistance by increasing the protein levels of OBRb. In addition, RSV downregulated the expression 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 demonstrate that RSV restored leptin sensitivity in a cellular model of hepatic steatosis in a SIRT1-independent manner.
Highlights
Dietary bioactive compounds are currently being investigated to complement therapeutic strategies to prevent or combat many diseases including non-alcoholic fatty liver disease (NAFLD) and leptin resistance [1,2,3]
The treatment of HepG2 cells with RSV for 20 min had no effect on pSTAT3 levels in any dose (Figure 1A) and even 10 μM of RSV significantly increased triglyceride (TAG) content compared to untreated cells (Figure 1B)
These results suggest that the delipidating effect of RSV is at least partially mediated by the increase in pSTAT3 and that leptin signalling is crucial to maintaining correct lipid metabolism in these cells
Summary
Dietary bioactive compounds are currently being investigated to complement therapeutic strategies to prevent or combat many diseases including non-alcoholic fatty liver disease (NAFLD) and leptin resistance [1,2,3]. In this sense, functional foods are gaining attention and more research is continually being performed to support new health claims. RSV has been indicated to have a wide range of biological effects, including cardioprotective, anticancer, anti-inflammatory, and antioxidant properties [8,9]. The exact mechanisms by which RSV exerts its beneficial effects are still unclear and require more research
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