Nutrition and Health Substantiation Group, Nutrition and Health Program, Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Adelaide, South Australia, Australia.
Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom.
Nutr Rev. 2020 Apr 1;78(4):261-277. doi: 10.1093/nutrit/nuz056.
Diet-induced hypothalamic inflammation, which leads to hypothalamic dysfunction and a loss of regulation of energy balance, is emerging as a potential driver of obesity. Excessive intake of long-chain saturated fatty acids is held to be the causative dietary component in hypothalamic inflammation. This review summarizes current evidence on the role of long-chain saturated fatty acids in promoting hypothalamic inflammation and the related induction of central insulin and leptin insensitivity. Particularly, the present review focuses on the molecular mechanisms linking long-chain saturated fatty acids and hypothalamic inflammation, emphasizing the metabolic fate of fatty acids and the resulting lipotoxicity, which is a key driver of hypothalamic dysfunction. In conclusion, long-chain saturated fatty acids are key nutrients that promote hypothalamic inflammation and dysfunction by fostering the build-up of lipotoxic lipid species, such as ceramide. Furthermore, when long-chain saturated fatty acids are consumed in combination with high levels of refined carbohydrates, the proinflammatory effects are exacerbated via a mechanism that relies on the formation of advanced glycation end products.
饮食诱导的下丘脑炎症会导致下丘脑功能障碍和能量平衡调节失控，它正成为肥胖的一个潜在驱动因素。过量摄入长链饱和脂肪酸被认为是引起下丘脑炎症的饮食因素。本综述总结了长链饱和脂肪酸在促进下丘脑炎症以及相关的中枢性胰岛素和瘦素抵抗中的作用的现有证据。特别是，本综述侧重于将长链饱和脂肪酸与下丘脑炎症联系起来的分子机制，强调脂肪酸的代谢命运和由此产生的脂毒性，这是下丘脑功能障碍的关键驱动因素。总之，长链饱和脂肪酸是关键的营养物质，通过促进脂毒性脂质物质（如神经酰胺）的积累，促进下丘脑炎症和功能障碍。此外，当长链饱和脂肪酸与高水平的精制碳水化合物一起摄入时，通过一种依赖于晚期糖基化终产物形成的机制，炎症作用会加剧。
