Control of adipogenic commitment by a STAT3-VSTM2A axis.

White adipose tissue (WAT) is a dynamic organ that plays crucial roles in controlling metabolic homeostasis. During development and periods of energy excess, adipose progenitors are recruited and differentiate into adipocytes to promote lipid storage capability. The identity of adipose progenitors and the signals that promote their recruitment are still incompletely characterized. We have recently identified V-set and transmembrane domain-containing protein 2A (VSTM2A) as a novel protein enriched in preadipocytes that amplifies adipogenic commitment. Despite the emerging role of VSTM2A in promoting adipogenesis, the molecular mechanisms regulating expression in preadipocytes are still unknown. To define the molecular mechanisms controlling expression, we have treated preadipocytes with an array of compounds capable of modulating established regulators of adipogenesis. Here, we report that expression is positively regulated by PI3K/mTOR and cAMP-dependent signaling pathways and repressed by the MAPK pathway and the glucocorticoid receptor. By integrating the impact of all the molecules tested, we identified signal transducer and activator of transcription 3 (STAT3) as a novel downstream transcription factor affecting expression. We show that activation of STAT3 increased expression, whereas its inhibition repressed this process. In mice, we found that STAT3 phosphorylation is elevated in the early phases of WAT development, an effect that strongly associates with expression. Our findings identify STAT3 as a key transcription factor regulating expression in preadipocytes. cAMP-dependent and PI3K-mTOR signaling pathways promote the expression of . STAT3 is a key transcription factor that controls expression in preadipocytes. STAT3 is activated in the early phases of WAT development, an effect that strongly associates with expression.