下丘脑炎症对肥胖的调控作用及其机制

Regulation and mechanism of hypothalamic inflammation on obesity

肥胖的病因研究和干预目前已逐渐聚焦于中枢,尝试从源头上遏制肥胖的发生,下丘脑炎症在肥胖发生中一直是比较关注和悬而未决的科学问题。近期研究发现下丘脑炎症不仅可以导致能量失衡,同时也加重中枢胰岛素抵抗和瘦素抵抗,进而使周围组织脂肪蓄积,导致肥胖发生发展。同时高脂饮食诱导的下丘脑炎症先于体重增加和外周组织炎症发生,可能是饮食诱导的机体代谢异常的启动因素和助燃器。而下丘脑炎症的发生主要伴随着一系列复杂的能够快速激活的神经细胞,其中主要包括小胶质细胞、星型胶质细胞及伸长细胞,这些细胞是维持下丘脑代谢稳态及复杂调节网络的重要组成部分。并且研究也发现多种减重手段(减重手术、靶向药物、粪菌移植等)都能改善下丘脑炎症水平,因此,了解下丘脑炎症的作用机制以及不同神经细胞对肥胖的调控至关重要,有望将来找到干预和治疗肥胖更加有效和安全的方法。

Many studies of the etiology and intervention for obesity have gradually focused on the brain,trying to curb the occurrence of obesity from the source.Hypothalamic inflammation has been a concern and an unresolved scientific issue in the development of obesity.Studies have shown that hypothalamic inflammation not only impairs energy balance,but also increases obesity-related insulin and leptin resistance,further promotes peripheral tissues storing up fat cells,eventually leads to the development of obesity.In addition,hypothalamic inflammation occurs before weight-gain and peripheral tissue inflammation with high-fat diets.Therefore,more and more scholars believe that hypothalamic inflammation is an important cause of dietary-induced metabolic abnormalities.The occurrence of hypothalamic inflammation is mainly accompanied by a series of complex and rapidly-activated glial,including microglia,astrocytes,and tanycyte.These cells are responsible for maintaining hypothalamic metabolic homeostasis and making up the important components of the regulatory network.Moreover,multiple teams also found that a variety of weight-loss methods(e.g.bariatric surgery,targeted drugs,fecal microbiota transplantation,and so on)can improve hypothalamic inflammation levels.Therefore,it is important to understand the mechanism of hypothalamic inflammation through different neurons,which is expected to find a more effective and safer solution to intervene and treat obesity in the future.