Adaptive thermogenesis is a fundamental defense against obesity through energy dissipation, yet the molecular mechanisms that couple energy sensing to transcriptional control remain incompletely understood. Here, we identify Feimin as a key activator of adaptive thermogenesis that connects AMP-activated protein kinase (AMPK) signaling to nuclear transcriptional regulation in adipose tissue. Upon cold exposure, AMPK phosphorylates Feimin, promoting translocation of Feimin into the nucleus, where it directly interacts with PGC1α to drive thermogenic gene expression. Conversely, obesity attenuates Feimin phosphorylation and nuclear localization, leading to impaired thermogenic capacity. Adipose-specific Feimin knockout abolishes cold-induced thermogenesis and exacerbates diet-induced obesity, phenotypes that cannot be rescued by a nuclear localization-defective Feimin mutant. Together, these findings delineate an AMPK-Feimin-PGC1α signaling axis essential for thermogenic regulation and identify Feimin as a promising therapeutic target for obesity and metabolic disorders.
Keywords: AMPK; Feimin; PGC1α; thermogenesis.