慢性应激致肥胖的神经-免疫-代谢机制研究进展OA

Chronic stress disrupts the homeostasis of the neuro-endocrine-immune network,there-by promoting aberrant energy metabolism and obesity.This article reviews the mechanisms underlying chronic stress-induced obesity in terms of hormonal signaling,neural regulation and the metabolic-immune microenvironment.At the hormonal level,we focus on the hypothalamic-pituitary adrenal(HPA)axis and the tissue-specific metabolic actions of glucocorticoids(GCs).At the neural level,we highlight the bidirectional regulation of adipose tissue by neuropeptide Y(NPY),the integrative stress responses of pituitary adenylate cyclase-activating polypeptide(PACAP)across multiple brain regions,the functional alterations of agouti-related protein(AgRP)neurons,and the neural circuits governing feeding behavior.At the metabolic-immune interface,we discuss the roles of tryptophan metabolism,macrophage krüppel-like factor 9(KLF9)signaling,and gut microbial metabolites.Collectively,these studies elucidate the complex mechanisms by which chronic stress leads to obesity,spanning from molecular events to organismal behavioral changes.However,translating these mechanistic insights into clinical practice remains challenging,particularly in selective blockade of pathological stress signals while preserving the homeostatic functions of the HPA axis and the central orexigenic actions of NPY.Targeted modulation of peripheral NPY-mediated metabolic regulation is critical to precision interven-tions in chronic stress-induced obesity.