Recent progress in understanding hypothalamic regulation of energy homeostasis

In recent years, sustained changes in dietary patterns, lifestyle behaviors, and environmental stressors have led to a marked increase in the prevalence of metabolic disorders such as obesity and diabetes. Accumulating evidence indicates that dysfunction of metabolically relevant cells and neural circuits within the central nervous system, together with the resulting disruption of energy homeostasis, constitutes a fundamental pathological basis for the development and progression of chronic metabolic diseases. As the central hub of energy metabolism regulation, the hypothalamus integrates external environmental cues with endogenous metabolic signals through the coordinated actions of multiple nuclei, including the arcuate nucleus (ARC), paraventricular nucleus (PVN), and lateral hypothalamic area (LHA), thereby dynamically maintaining the balance between energy intake, storage, and expenditure. Elucidating the key molecular mechanisms and neural circuit architectures underlying neural control of energy metabolism, and targeting central regulatory nodes such as the hypothalamus on this basis, has emerged as a promising strategy for the systemic intervention of metabolic diseases. In this review, we focus on how the central nervous system senses and regulates energy information flow, with particular emphasis on the neuro-molecular and circuit mechanisms by which the hypothalamus governs energy homeostasis under physiological conditions and in metabolic disorders, providing a framework for future mechanistic studies and therapeutic development.