Huang Mingyue, Yang Xinyu, Wang Zhenzhen, Long Jianglan, Wang Aiting, Zhang Yi, Yan Dan
College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, People's Republic of China.
Beijing Key Laboratory of Bio-Characteristic Profiling for Evaluation of Rational Drug Use, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China.
Diabetes Metab Syndr Obes. 2021 Jun 30;14:2985-2999. doi: 10.2147/DMSO.S310166. eCollection 2021.
Autophagy has been reported to involve in the pathogenesis of type 2 diabetes mellitus (T2DM), which protects the insulin target tissues and pancreatic β-cells. However, autophagy is inhibited when the cells are lipid overload. That, in turn, increases the accumulation of fat. Lipotoxicity caused by excessive lipid accumulation contributes to pathogenesis of T2DM. Therefore, it is undeniable to break the vicious circles between lipid excess and autophagy deficiency. Lipophagy, a selective form of autophagy, is characterized by selective breakdown of lipid droplets (LDs). The nutritional status of cells contributes to the way of autophagy (selective or non-selective), while selective autophagy helps to accurately remove excess substances. It seems that lipophagy could be an effective means to decrease abnormal lipid accumulation that leads to insulin resistance and β-cell impairment by removing ectopic LDs. Based on this process, many natural compounds have been reported to decrease lipid accumulation in tissues through autophagy-lysosomal pathway, which gradually highlights the significance of lipophagy. In this review, we focus on the mechanisms that lipophagy improves T2DM and natural products that are applied to induce lipophagy. It is also suggested that natural herbs with rich contents of natural products inducing lipophagy would be potential candidates for alleviating T2DM.
据报道，自噬参与2型糖尿病（T2DM）的发病机制，它对胰岛素靶组织和胰腺β细胞具有保护作用。然而，当细胞出现脂质过载时，自噬会受到抑制。这反过来又会增加脂肪的积累。由过量脂质积累引起的脂毒性会促进T2DM的发病机制。因此，打破脂质过剩与自噬缺陷之间的恶性循环是不可否认的。脂质自噬是自噬的一种选择性形式，其特征是脂质小滴（LDs）的选择性分解。细胞的营养状态决定了自噬的方式（选择性或非选择性），而选择性自噬有助于准确清除多余物质。脂质自噬似乎可能是一种有效的手段，通过清除异位脂质小滴来减少导致胰岛素抵抗和β细胞损伤的异常脂质积累。基于这一过程，许多天然化合物已被报道可通过自噬-溶酶体途径减少组织中的脂质积累，这逐渐凸显了脂质自噬的重要性。在这篇综述中我们重点关注脂质自噬改善T2DM的机制以及用于诱导脂质自噬的天然产物。还表明富含诱导脂质自噬天然产物的天然草药可能是缓解T2DM的潜在候选物。
