Lsd1 prevents age-programed loss of beige adipocytes

Proc Natl Acad Sci U S A.            online article

Over time, beige adipocytes gain a white adipocyte morphology and lose their thermogenic activity. Here we show that levels of the epigenetic eraser lysine-specific demethylase 1 (Lsd1) decrease in aging inguinal white adipose tissue concomitantly with beige fat cell decline. Maintaining adipocyte-specific expression of Lsd1 in transgenic mice preserves the pool of beige adipocytes in old mice. Vice versa, using GFP reporter mice, we traced the fate of beige adipocytes and showed that adipocyte-specific loss of Lsd1 results in a premature beige-to-white adipocyte transition in vivo. Maintenance of beige adipocytes is mediated by the Lsd1 target gene peroxisome proliferator-activated receptor α (Ppara) and pharmacological activation of Ppara rescues the loss of beige adipocytes in Lsd1-KO mice. Together, we identified Lsd1 as a regulator of beige adipocyte maintenance.