Yang Jiali, Ran Yunhui, Yang Yonghui, Song Shuyi, Wu Yahong, Qi Yuanming, Gao Yanfeng, Li Guodong
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
School of Life Sciences, Zhengzhou University, Zhengzhou, China.
Front Pharmacol. 2021 Jan 21;11:606514. doi: 10.3389/fphar.2020.606514. eCollection 2020.
In obesity, macrophages and other immune cells accumulate in organs affected by insulin, leading to chronic inflammation and insulin resistance. 4-Hydroxyisoleucine (4-HIL) is a non-protein amino acid found in fenugreek seeds. 4-HIL enhances insulin sensitivity, but its mechanism is still unclear. In this study, 4-HIL intervention reduced weight gain, liver steatosis, and dyslipidemia; moreover, it increased systemic insulin sensitivity and improved insulin resistance in mice. Importantly, after administration, the accumulation of M1 like CD11c macrophages and inflammation in the liver and adipose tissue were reduced in the mice. 4-HIL also reduced the proportion of CD11c macrophages among bone marrow-derived macrophages, which were induced . These observations demonstrate a new role of 4-HIL in insulin resistance in hepatocytes and adipocytes. 4-HIL inhibits obesity-related insulin resistance by reducing inflammation and regulating the state of M1/M2 macrophages.
在肥胖症中，巨噬细胞和其他免疫细胞会在受胰岛素影响的器官中积聚，导致慢性炎症和胰岛素抵抗。4-羟基异亮氨酸（4-HIL）是一种存在于胡芦巴种子中的非蛋白质氨基酸。4-HIL可增强胰岛素敏感性，但其机制尚不清楚。在本研究中，4-HIL干预减少了体重增加、肝脏脂肪变性和血脂异常；此外，它还提高了小鼠的全身胰岛素敏感性并改善了胰岛素抵抗。重要的是，给药后，小鼠肝脏和脂肪组织中M1样CD11c巨噬细胞的积聚及炎症减少。4-HIL还降低了诱导产生的骨髓来源巨噬细胞中CD11c巨噬细胞的比例。这些观察结果证明了4-HIL在肝细胞和脂肪细胞胰岛素抵抗中的新作用。4-HIL通过减轻炎症和调节M1/M2巨噬细胞状态来抑制肥胖相关的胰岛素抵抗。
