Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University, Changsha, 410078, Hunan, China.
Plant Foods Hum Nutr. 2023 Dec;78(4):720-727. doi: 10.1007/s11130-023-01108-z. Epub 2023 Sep 29.
Sesamol is the major bioactive constituent isolated from sesame seeds and has a variety of bioactivities. However, its role and mechanism in liver insulin resistance remain unknown. The current study was designed to investigate the underlying adipose-liver crosstalk mechanism of sesamol ameliorating hepatic insulin sensitivity. The therapeutic effect of sesamol was evaluated in high-fat diet (HFD)-fed C57BL/6 J mice (100 mg/kg for 8 weeks, XYGW-2021-75) and the mechanism was further explored in HepG2 cells with/without adiponectin and adenosine 5 '-monophosphate-activated protein kinase (AMPK) inhibitor administration. Our in vivo data showed that sesamol reduced hepatic insulin resistance in HFD-induced mice with obesity by modulating protein expression levels of glycogen synthase (GS), phosphoenolpyruvate carboxykinase (PEPCK) and protein kinase B (AKT). Moreover, sesamol not only increased the serum and adipose tissue adiponectin concentrations but also activated the phosphorylation of AMPK in the liver. Furthermore, in vitro studies using recombinant human adiponectin and an AMPK inhibitor revealed that adiponectin and sesamol have a synergic impact on increasing glycogenesis and reducing gluconeogenesis, of which the effects could be attenuated by the AMPK inhibitor. Taken together, our results suggested that sesamol stimulated adiponectin secretion from adipocytes, whereby exhibited a co-effect on activating the downstream signal of hepatic AMPK, resulting in the alleviation of hepatic insulin resistance. The novel findings of sesamol on hepatic effects provides prospective therapeutic approaches to treat insulin resistance.
芝麻酚是从芝麻种子中分离得到的主要生物活性成分，具有多种生物活性。然而，其在肝脏胰岛素抵抗中的作用和机制尚不清楚。本研究旨在探讨芝麻酚改善肝脏胰岛素敏感性的脂肪-肝脏相互作用的潜在机制。采用高脂肪饮食（HFD）喂养的 C57BL/6J 小鼠（100mg/kg，8 周，XYGW-2021-75）评估芝麻酚的治疗效果，并进一步在 HepG2 细胞中探讨其机制，包括添加或不添加脂联素和腺苷酸活化蛋白激酶（AMPK）抑制剂。我们的体内数据表明，芝麻酚通过调节糖原合酶（GS）、磷酸烯醇丙酮酸羧激酶（PEPCK）和蛋白激酶 B（AKT）的蛋白表达水平，减轻了肥胖 HFD 诱导的小鼠肝脏胰岛素抵抗。此外，芝麻酚不仅增加了血清和脂肪组织中脂联素的浓度，还激活了肝脏中 AMPK 的磷酸化。此外，使用重组人脂联素和 AMPK 抑制剂的体外研究表明，脂联素和芝麻酚对增加糖生成和减少糖异生具有协同作用，其中 AMPK 抑制剂可减弱这种作用。综上所述，我们的研究结果表明，芝麻酚刺激脂肪细胞分泌脂联素，进而激活肝脏 AMPK 的下游信号，从而减轻肝脏胰岛素抵抗。芝麻酚对肝脏作用的新发现为治疗胰岛素抵抗提供了有前景的治疗方法。
