Mazibuko-Mbeje Sithandiwe E, Ziqubu Khanyisani, Dludla Phiwayinkosi V, Tiano Luca, Silvestri Sonia, Orlando Patrick, Nyawo Thembeka A, Louw Johan, Kappo Abidemi P, Muller Christo J F
Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, 7505, South Africa.
Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa.
Metabol Open. 2020 Apr 28;6:100037. doi: 10.1016/j.metop.2020.100037. eCollection 2020 Jun.
Stimulation of fat browning using natural bioactive products is regarded as one of the promising approaches to treat obesity and insulin resistance. Here, we investigated the physiological effects of isoorientin on glucose uptake and lipid accumulation in insulin resistant 3T3-L1 adipocytes. To achieve this, 3T3-L1 adipocytes were exposed to 0.75 mM palmitate for 24 h, to induce insulin resistance, before treatment with 10 μM isoorientin or the comparative controls such as CL-316,243 (10 μM), pioglitazone (10 μM) and compound C (1 μM) for 4 h. Relevant bioassays and Western blot analysis were conducted on these insulin resistant cells. Our results showed that palmitate exposure could induce insulin resistance and mitochondrial dysfunction as measured by reduction in glucose uptake and impaired mitochondrial bioenergetics parameters. However, treatment with isoorientin reversed these effects by improving glucose uptake, blocking lipid accumulation, and modulating the process of mitochondrial respiration. Mechanistically, isoorientin could mediate lipid metabolism by activating 5' AMP-activated protein kinase (AMPK), while also effectively modulating the expression of genes involved in fat browning such as peroxisome proliferator-activated receptor gamma (PPAR)γ/α and uncoupling protein 1 (UCP1). In conclusion, isoorientin impacts insulin resistance in vitro by improving glucose uptake and mitochondrial function, consistent to modulating the expression of genes involved in energy metabolism and fat browning.
使用天然生物活性产品刺激脂肪褐变被认为是治疗肥胖症和胰岛素抵抗的一种有前景的方法。在此，我们研究了异荭草素对胰岛素抵抗的3T3-L1脂肪细胞中葡萄糖摄取和脂质积累的生理影响。为此，在使用10 μM异荭草素或比较对照物如CL-316,243（10 μM）、吡格列酮（10 μM）和化合物C（1 μM）处理4小时之前，将3T3-L1脂肪细胞暴露于0.75 mM棕榈酸24小时以诱导胰岛素抵抗。对这些胰岛素抵抗细胞进行了相关的生物测定和蛋白质印迹分析。我们的结果表明，如通过葡萄糖摄取减少和线粒体生物能量学参数受损所测量的，棕榈酸暴露可诱导胰岛素抵抗和线粒体功能障碍。然而，异荭草素处理通过改善葡萄糖摄取、阻止脂质积累和调节线粒体呼吸过程逆转了这些影响。从机制上讲，异荭草素可通过激活5'腺苷酸活化蛋白激酶（AMPK）介导脂质代谢，同时还能有效调节参与脂肪褐变的基因如过氧化物酶体增殖物激活受体γ（PPAR）γ/α和解偶联蛋白1（UCP1）的表达。总之，异荭草素通过改善葡萄糖摄取和线粒体功能在体外影响胰岛素抵抗，这与调节参与能量代谢和脂肪褐变的基因表达一致。
