| First Author | Lapid K | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 5196 | PubMed ID | 25330806 |
| Mgi Jnum | J:278385 | Mgi Id | MGI:6296178 |
| Doi | 10.1038/ncomms6196 | Citation | Lapid K, et al. (2014) Oestrogen signalling in white adipose progenitor cells inhibits differentiation into brown adipose and smooth muscle cells. Nat Commun 5:5196 |
| abstractText | Oestrogen, often via oestrogen receptor alpha (ERalpha) signalling, regulates metabolic physiology, highlighted by post-menopausal temperature dysregulation (hot flashes), glucose intolerance, increased appetite and reduced metabolic rate. Here we show that ERalpha signalling has a role in adipose lineage specification in mice. ERalpha regulates adipose progenitor identity and potency, promoting white adipogenic lineage commitment. White adipose progenitors lacking ERalpha reprogramme and enter into smooth muscle and brown adipogenic fates. Mechanistic studies highlight a TGFbeta programme involved in progenitor reprogramming downstream of ERalpha signalling. The observed reprogramming has profound metabolic outcomes; both female and male adipose-lineage ERalpha-mutant mice are lean, have improved glucose sensitivity and are resistant to weight gain on a high-fat diet. Further, they are hypermetabolic, hyperphagic and hyperthermic, all consistent with a brown phenotype. Together, these findings indicate that ERalpha cell autonomously regulates adipose lineage commitment, brown fat and smooth muscle cell formation, and systemic metabolism, in a manner relevant to prevalent metabolic diseases. |
