ERα activates NAMPT/IL-33 signaling to enhance beige thermogenesis and metabolic fitness.

ABSTRACT: Beige adipocytes are inducible thermogenic fat cells that emerge within white adipose tissue (WAT) in response to thermogenic stimuli and confer metabolic benefits. However, obesity impairs the generation of beige adipocytes, and the underlying mechanisms remain poorly understood. Here, we show that obesity leads to a loss of adipose progenitor cells (APCs) in WAT, accompanied by reduced estrogen (E2) levels and nicotinamide phosphoribosyltransferase (NAMPT) expression. Supplementation with E2 or nicotinamide mononucleotide (NMN), an NAMPT-derived nicotinamide adenine dinucleotide (NAD⁺) precursor, restores beige adipogenesis in diet-induced obese mice. Mechanistically, estrogen receptor α (ERα) in APCs is required for beige fat formation by promoting Nampt transcription.

SUBMITTER: Hu R 

PROVIDER: S-EPMC12778055 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature