Lipolysis-Derived Linoleic Acid Drives Beige Fat Progenitor Cell Proliferation via CD36

De novo beige adipocyte biogenesis involves the proliferation of progenitor cells in white adipose tissue (WAT); however, what regulates this process remains unclear. Here, we report that WAT lipolysis-derived linoleic acid is a potent trigger of beige progenitor cell proliferation following pathophysiological stimuli, including cold acclimation and burn injury. A subset of adipocyte progenitors, as marked by cell surface markers PDGFRα or Sca1 and CD81, harbored cristae-rich mitochondria and actively imported linoleic acid via a fatty acid transporter CD36. Linoleic acid was oxidized as fuel in the mitochondria but also utilized for the synthesis of arachidonic acid-derived signaling entities, such as prostaglandin D2. Significantly, oral supplementation of linoleic acid was sufficient to stimulate beige progenitor cell proliferation even under a thermoneutral condition, in a CD36-dependent manner. Together, the present study provides a mechanistic foundation for a nutritional intervention that promotes de novo beige fat biogenesis.