Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Life Sci. 2020 Oct 1;258:118222. doi: 10.1016/j.lfs.2020.118222. Epub 2020 Aug 6.
We previously reported that fenugreek-derived 4-hydroxyisoleucine ameliorates insulin resistance via regulation of TNF-α converting enzyme (TACE) expression. In the present study, we further investigate the effects and mechanisms of fenugreek on obesity-induced inflammation and insulin signaling in the high-fat diet (HFD)-challenged obese mice.
After 12 weeks of HFD intervention, mice were treated with the low or high dosages of fenugreek. Serum levels of glucose, insulin, lipid profile, inflammation cytokines, and adipokines were detected. Macrophage infiltration and adipose tissue morphology were observed. Western blot was conducted to investigate the expressions of inactive rhomboid 2 (iRhom2) and TACE as well as other signaling pathways in subcutaneous adipose tissue.
We showed that fenugreek significantly suppressed body weight gain and fat accumulation in HFD-challenged obese mice. Meanwhile, fasting glucose, insulin, and HOMA-IR in fenugreek-treated mice were remarkably decreased, which were properly explained by fenugreek-induced activation of the insulin receptor signaling pathway. Moreover, the anti-inflammatory properties of fenugreek were shown by the decrease of systemic and local expressions of pro-inflammatory cytokines as well as reduced macrophage infiltration into adipose tissue. Additionally, fenugreek markedly deactivated NF-κB and JNK pathways. Finally, we demonstrated that fenugreek strikingly repressed the transcriptions and expressions of iRhom2 and TACE.
Fenugreek shows an encouraging and promising property in ameliorating insulin resistance and suppressing inflammation in obesity, which might be realized by fenugreek-mediated inhibition of iRhom2/TACE axis-facilitated TNF-α release from adipocytes.
我们之前报道过，葫芦巴衍生的 4-羟基异亮氨酸通过调节肿瘤坏死因子-α转化酶（TACE）的表达来改善胰岛素抵抗。在本研究中，我们进一步研究了葫芦巴对高脂肪饮食（HFD）诱导肥胖小鼠的肥胖相关炎症和胰岛素信号的影响和机制。
在 HFD 干预 12 周后，用低剂量或高剂量的葫芦巴对小鼠进行治疗。检测血清中葡萄糖、胰岛素、血脂谱、炎症细胞因子和脂肪因子的水平。观察巨噬细胞浸润和脂肪组织形态。通过 Western blot 检测皮下脂肪组织中无活性的类 2 环指蛋白（iRhom2）和 TACE 以及其他信号通路的表达。
我们表明，葫芦巴显著抑制了 HFD 诱导肥胖小鼠的体重增加和脂肪堆积。同时，葫芦巴治疗组小鼠的空腹血糖、胰岛素和 HOMA-IR 显著降低，这与葫芦巴诱导的胰岛素受体信号通路的激活是一致的。此外，葫芦巴的抗炎作用表现为全身和局部促炎细胞因子表达的减少，以及脂肪组织中巨噬细胞浸润的减少。此外，葫芦巴明显使 NF-κB 和 JNK 通路失活。最后，我们证明葫芦巴显著抑制了 iRhom2 和 TACE 的转录和表达。
葫芦巴在改善肥胖引起的胰岛素抵抗和抑制炎症方面表现出令人鼓舞和有前景的特性，这可能是通过葫芦巴介导的抑制 iRhom2/TACE 轴促进脂肪细胞中 TNF-α释放来实现的。
