Longevity & AgingFemale BAT Burns More Energy Due to PGC-1α Driving Unique Phospholipid Synthesis
Brown adipose tissue (BAT) generates heat and protects against metabolic disease, and females consistently show higher BAT activity than males. This mouse study reveals why: the transcriptional coactivator PGC-1α is more highly expressed in female BAT, where it drives a sex-specific program linking estrogen signaling to de novo lipogenesis and specialized phospholipid synthesis. Female-only knockout of PGC-1α collapsed mitochondrial cristae structure, reduced thermogenic capacity, and impaired cold tolerance — effects absent in males. The key intermediary is ChREBPβ, a lipogenic transcription factor regulated by estrogen that controls synthesis of ether-linked phosphatidylethanolamine and tetra-linoleoyl cardiolipin — lipids critical for mitochondrial membrane integrity and function. These findings map a female-specific molecular circuit that may help explain women's relative metabolic advantage before menopause.
