| First Author | Ahluwalia A | Year | 2020 |
| Journal | Endocrinology | Volume | 161 |
| Issue | 11 | PubMed ID | 32976570 |
| Mgi Jnum | J:296579 | Mgi Id | MGI:6468185 |
| Doi | 10.1210/endocr/bqaa175 | Citation | Ahluwalia A, et al. (2020) Mechanisms by Which Membrane and Nuclear ER Alpha Inhibit Adipogenesis in Cells Isolated From Female Mice. Endocrinology 161(11) |
| abstractText | Mesenchymal stem cells can differentiate into mature chondrocytes, osteoblasts, and adipocytes. Excessive and dysfunctional visceral adipocytes increase upon menopause and importantly contribute to altered metabolism in postmenopausal women. We previously showed both plasma membrane and nuclear estrogen receptors alpha (ERalpha) with endogenous estrogen are required to suppress adipogenesis in vivo. Here we determined mechanisms by which these liganded ER pools collaborate to inhibit the peroxisome proliferator-activated gamma (PPARgamma) gene and subsequent progenitor differentiation. In 3T3-L1 pre-adipocytes and adipose-derived stem cells (ADSC), membrane ERalpha signaled through phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) to enhance ERalpha nuclear localization, importantly at the PPARgamma gene promoter. AKT also increased overall abundance and recruitment of co-repressors GATA3, beta-catenin, and TCF4 to the PPARgamma promoter. Membrane ERalpha signaling additionally enhanced wingless-integrated (Wnt)1 and 10b expression. The components of the repressor complex were required for estrogen to inhibit rosiglitazone-induced differentiation of ADSC and 3T3-L1 cells to mature adipocytes. These mechanisms whereby ER cellular pools collaborate to inhibit gene expression limit progenitor differentiation to mature adipocytes. |
