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Merck

Lipolysis-derived linoleic acid drives beige fat progenitor cell proliferation.

Developmental cell (2022-12-07)
Ichitaro Abe, Yasuo Oguri, Anthony R P Verkerke, Lauar B Monteiro, Carly M Knuth, Christopher Auger, Yunping Qiu, Gregory P Westcott, Saverio Cinti, Kosaku Shinoda, Marc G Jeschke, Shingo Kajimura
RÉSUMÉ

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 in mouse models but also in human tissues, WAT lipolysis-derived linoleic acid triggers beige progenitor cell proliferation following cold acclimation, β3-adrenoceptor activation, 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 not only was oxidized as fuel in the mitochondria but also was utilized for the synthesis of arachidonic acid-derived signaling entities such as prostaglandin D2. Oral supplementation of linoleic acid was sufficient to stimulate beige progenitor cell proliferation, even under thermoneutral conditions, in a CD36-dependent manner. Together, this study provides mechanistic insights into how diverse pathophysiological stimuli, such as cold and burn injury, promote de novo beige fat biogenesis.

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