This study highlights a cross-system regulatory axis linking the Ghrelin-GHSR pathway to hypothalamic POMC neuronal activity and peripheral CD4+ T-cell metabolic reprogramming in obesity-associated T2DM. While SG is clinically effective, its weight-independent mechanisms remain incompletely defined. Here, our data support that SG is associated with a coordinated shift in CD4+ T-cell energetics from glycolysis toward oxidative phosphorylation through suppression of Ghrelin-GHSR signaling, thereby helping restore Treg/Th17 balance and systemic redox homeostasis.