Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain.
Human Nutrition Unit, Department of Food and Drugs, University of Parma, 43125 Parma, Italy.
Int J Mol Sci. 2019 Dec 12;20(24):6282. doi: 10.3390/ijms20246282.
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 () and () 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.
瘦素与其肝脏最长受体（OBRb）的相互作用促进信号转导和转录激活因子 3（STAT3）的磷酸化，从而保护肝脏免受脂质积累。然而，肝脂肪变性会破坏瘦素信号，导致瘦素抵抗。一种有前途的解决此问题的策略是使用生物活性化合物，如多酚。由于白藜芦醇（RSV）是肝脏脂质稳态的调节剂，我们研究了不同剂量的 RSV 是否能恢复棕榈酸诱导的脂肪变性人肝癌（HepG2）细胞中适当的瘦素作用和脂肪积累。分析了 RSV 的代谢和参与瘦素信号的分子的表达。RSV 在 10 μM 浓度下在 24 小时内完全代谢为白藜芦醇-3-硫酸盐，并通过增加 OBRb 的蛋白水平来抵抗瘦素抵抗。此外，RSV 下调了包括（）和（）在内的生脂基因的表达，而 Sirtuin-1（SIRT1）酶活性没有任何显著变化。这些结果表明，RSV 以 SIRT1 独立的方式在肝脂肪变性的细胞模型中恢复了瘦素敏感性。
