This study investigates the role of the circadian transcription factor ARNTL2 in human adipogenesis. ARNTL2 mRNA is downregulated in adipose stem/progenitor cells (ASCs) after weight loss, while ARNTL2 protein is induced during adipogenic differentiation. ARNTL2 is maintained by mTOR and MAPK signaling, yet it inhibits these pathways, creating a feedback loop. Overexpression of ARNTL2 represses adipogenesis by degrading ARNTL1, inhibiting KLF15, and downregulating the MAPK-C/EBPβ axis. Weight loss increases ARNTL2 protein in subcutaneous white adipose tissue. Therefore, ARNTL2 is a weight-loss-regulated inhibitor of adipogenesis, potentially offering new strategies to combat obesity.

Markus Mandl, Hans P. Viertler, Maria Zopoglou, Maria C. Mitterberger-Vogt, Juliane Gasser, Florian M. Hatzmann, Tina Rauchenwald, Marit E. Zwierzina, Monika Mattesich, Alexander K. H. Weiss, Lorenza Mottes, Camille Brucker, Petra Waldegger, Gerhard Pierer, Werner Zwerschke