Lsd1, a metabolic sensor of environment requirements that prevents adipose tissue from aging

Understanding development and maintenance of beige adipocytes provide exciting insights in establishing novel therapies against obesity and obesity-associated disorders. Lysine-specific demethylase 1 (Lsd1) is an epigenetic eraser required for differentiation and function of adipocytes. Lsd1 is involved in early commitment of preadipocytes, but dispensable for terminal differentiation of white adipose tissue (WAT). In mature adipocytes, Lsd1 responds to different environmental stimuli to alter metabolic function and enable proper thermogenic and oxidative response. Exposure to cold leads to Lsd1 upregulation and subsequent beiging of WAT. Oppositely, Lsd1 levels decline during aging resulting in a conversion of beige into white adipocytes, associated with loss of thermogenic properties of WAT. Lsd1 maintains beige adipocytes by controlling the expression of the nuclear receptor peroxisome proliferator-activated receptor α. In summary, our studies not only provided insights into the mechanism of age-related beige-to-white adipocyte transition, but also established Lsd1 as a sensor that enables thermogenic response in WAT.