Nutrition and Health Substantiation Group, Nutrition and Health Program, Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Adelaide, SA, 5000, Australia.
Adelaide Medical School, The University of Adelaide, Adelaide, SA, 5000, Australia.
Mol Nutr Food Res. 2021 Jan;65(1):e1900934. doi: 10.1002/mnfr.201900934. Epub 2020 Apr 20.
Advanced glycation end products (AGEs) are a heterogeneous group of molecules produced, non-enzymatically, from the interaction between reducing sugars and the free amino groups of proteins, nucleic acids, and lipids. AGEs are formed as a normal consequence of metabolism but can also be absorbed from the diet. They have been widely implicated in the complications of diabetes affecting cardiovascular health, the nervous system, eyes, and kidneys. Increased levels of AGEs are also detrimental to metabolic health and may contribute to the metabolic abnormalities induced by the Western diet, which is high in processed foods and represents a significant source of AGEs. While increased AGE levels are a consequence of diabetic hyperglycaemia, AGEs themselves activate signaling pathways, which compromise insulin signaling and pancreatic β-cell function, thus, contributing to the development of type 2 diabetes mellitus (T2DM). Furthermore, AGEs may also contribute to the obesogenic effects of the Western diet by promoting hypothalamic inflammation and disrupting the central control of energy balance. Here, the role of dietary AGEs in metabolic dysfunction is reviewed with a focus on the mechanisms underpinning their detrimental role in insulin resistance, pancreatic β-cell dysfunction, hypothalamic control of energy balance, and the pathogenesis of T2DM and obesity.
糖基化终产物(AGEs)是一组不均一的分子,它们通过还原糖与蛋白质、核酸和脂质的游离氨基基团之间的非酶促反应产生。AGEs 是代谢的正常产物,但也可以从饮食中吸收。它们与影响心血管健康、神经系统、眼睛和肾脏的糖尿病并发症广泛相关。AGE 水平的升高也不利于代谢健康,并可能导致西方饮食引起的代谢异常,西方饮食中加工食品含量高,是 AGE 的重要来源。虽然 AGE 水平的升高是糖尿病高血糖的结果,但 AGE 本身会激活信号通路,损害胰岛素信号和胰岛 β 细胞功能,从而导致 2 型糖尿病(T2DM)的发生。此外,AGEs 还可能通过促进下丘脑炎症和破坏能量平衡的中枢控制,对西方饮食的肥胖效应产生影响。本文重点讨论了饮食 AGE 在代谢功能障碍中的作用,以及它们在胰岛素抵抗、胰岛 β 细胞功能障碍、能量平衡的下丘脑控制和 T2DM 及肥胖发病机制中的有害作用的机制。