Brain Nutrient Sensing: A Unifying Framework.

Whole-body nutrient homeostasis is critical for healthy growth, successful reproduction, and survival. We propose a conceptual framework emphasizing the role of brain nutrient sensing in mediating adaptive responses for the maintenance of nutrient homeostasis. Specialized brain nutrient-sensing cells monitor nutrients and meal-related signals, provide feedback responses to maintain internal nutrient availability, and adapt physiological functions according to environmental nutrient fluctuations. Maladaptive functioning of these pathways may underlie multiple pathophysiological conditions, including cardiometabolic and neurodegenerative diseases. By examining recent advances, this review highlights the importance of brain nutrient sensing in adaptive systemic physiology and behavior, exploring the potential of these neural pathways as therapeutic targets extending beyond obesity management. Ultimately, the goal of this review is to synthesize current evidence into a coherent framework that guides new mechanistic hypotheses, facilitating deeper investigation into how brain nutrient sensing influences health and contributes to disease pathogenesis.