Agroprocessing and Natural Products Division, CSIR-National Institute for Interdisciplinary Science and Technology (NIIST), Thiruvananthapuram, Kerala, India, 695019.
Agroprocessing and Natural Products Division, CSIR-National Institute for Interdisciplinary Science and Technology (NIIST), Thiruvananthapuram, Kerala, India, 695019.
Int Immunopharmacol. 2017 Jan;42:209-217. doi: 10.1016/j.intimp.2016.11.019. Epub 2016 Dec 7.
Obesity leads to inflammation and insulin resistance in adipose tissue. Hypoxia, observed in obese adipose tissue is suggested as a major cause of inflammation and insulin resistance in obesity. However, the role of hypoxia in adipose tissue during obesity and insulin resistance was not well established. Here we mainly explored the crosstalk between hypoxia induced inflammation, and insulin resistance and also secretion of angiogenic factors in 3T3-L1 adipocytes and possible reversal with bilobalide. Hypoxia for 24h significantly (P≤0.05) increased the secretion of MCP-1 (4.59 fold), leptin (2.96 fold) and reduced adiponectin secretion (2.93 fold). In addition, the mRNA level of resistin (6.8 fold) and TLR4 receptors (8.8 fold) was upregulated in hypoxic adipocytes. The release of inflammatory cytokines and expression of TLR4 receptors led to activation of JNK and NF-κB signalling. We further investigated the effects of JNK and NF-κB activation on insulin signalling receptors. The present study showed increased (P≤0.05) serine 307 phosphorylation of IRS-1 (1.9 fold) and decreased expression of IRS-2 (0.53 fold) in hypoxic group showing hypoxia induced impairment in insulin signalling. Hypoxia significantly (P≤0.05) increased basal glucose uptake (3.3 fold) as well as GLUT-1 expression in adipocytes indicating GLUT-1 mediated glucose uptake. Hypoxia for 24h significantly increased (P≤0.05) the expression of angiogenic factors. Bilobalide protected adipocytes from hypoxia induced inflammation and insulin resistance mainly by reducing inflammatory adipokine secretion, improving adiponectin secretion, reducing NF-κB/JNK activation, and inhibiting serine phosphorylation of IRS-1 receptors of insulin signalling pathway.
肥胖可导致脂肪组织炎症和胰岛素抵抗。在肥胖中，观察到的缺氧被认为是炎症和胰岛素抵抗的主要原因。然而，肥胖和胰岛素抵抗期间脂肪组织缺氧的作用尚未得到很好的确定。在这里，我们主要探讨了缺氧诱导的炎症和胰岛素抵抗之间的串扰，以及 3T3-L1 脂肪细胞中血管生成因子的分泌，以及白果内酯对此的可能逆转作用。缺氧 24 小时可显著（P≤0.05）增加单核细胞趋化蛋白-1（MCP-1）（4.59 倍）、瘦素（2.96 倍）的分泌，并减少脂联素的分泌（2.93 倍）。此外，缺氧脂肪细胞中的抵抗素（6.8 倍）和 TLR4 受体（8.8 倍）mRNA 水平上调。炎症细胞因子的释放和 TLR4 受体的表达导致 JNK 和 NF-κB 信号通路的激活。我们进一步研究了 JNK 和 NF-κB 激活对胰岛素信号受体的影响。本研究表明，缺氧组 IRS-1 的丝氨酸 307 磷酸化增加（P≤0.05）（1.9 倍），IRS-2 表达减少（0.53 倍），表明缺氧诱导胰岛素信号受损。缺氧可显著（P≤0.05）增加基础葡萄糖摄取（3.3 倍）以及脂肪细胞中 GLUT-1 的表达，表明 GLUT-1 介导的葡萄糖摄取。缺氧 24 小时可显著（P≤0.05）增加血管生成因子的表达。白果内酯主要通过减少炎症性脂肪因子的分泌、改善脂联素的分泌、减少 NF-κB/JNK 激活以及抑制胰岛素信号通路 IRS-1 受体的丝氨酸磷酸化，来保护脂肪细胞免受缺氧诱导的炎症和胰岛素抵抗。
