Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Faculté de Médecine, Université Laval, Québec, Canada.
Centre de recherche sur le cancer de l'Université Laval, Université Laval, Québec, Canada.
Am J Physiol Endocrinol Metab. 2021 Feb 1;320(2):E259-E269. doi: 10.1152/ajpendo.00314.2020. Epub 2020 Nov 16.
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.
白色脂肪组织 (WAT) 是一种具有重要代谢调节作用的动态器官。在发育和能量过剩期间，脂肪祖细胞被募集并分化为脂肪细胞，以促进脂质储存能力。脂肪祖细胞的身份以及促进其募集的信号仍不完全清楚。我们最近发现 V -set 和跨膜域蛋白 2A（VSTM2A）作为一种在脂肪前体细胞中丰富的新型蛋白，可放大脂肪生成的承诺。尽管 VSTM2A 在促进脂肪生成中的作用不断涌现，但调节脂肪前体细胞中表达的分子机制仍不清楚。为了定义控制表达的分子机制，我们用一系列能够调节已确立的脂肪生成调节剂的化合物处理脂肪前体细胞。在这里，我们报告表达受 PI3K/mTOR 和 cAMP 依赖性信号通路的正调控，受 MAPK 通路和糖皮质激素受体的负调控。通过整合所有测试分子的影响，我们确定信号转导和转录激活因子 3（STAT3）作为一种影响表达的新型下游转录因子。我们表明 STAT3 的激活增加了表达，而其抑制则抑制了这一过程。在小鼠中，我们发现 STAT3 磷酸化在 WAT 发育的早期阶段升高，这种效应与表达强烈相关。我们的研究结果确定 STAT3 为调节脂肪前体细胞中表达的关键转录因子。cAMP 依赖性和 PI3K-mTOR 信号通路促进的表达。STAT3 是控制脂肪前体细胞中表达的关键转录因子。STAT3 在 WAT 发育的早期阶段被激活，这种效应与表达强烈相关。
