Oestrogen signalling in white adipose progenitor cells inhibits differentiation into brown adipose and smooth muscle cells.

ABSTRACT: Oestrogen, often via oestrogen receptor alpha (ER?) signalling, regulates metabolic physiology, highlighted by post-menopausal temperature dysregulation (hot flashes), glucose intolerance, increased appetite and reduced metabolic rate. Here we show that ER? signalling has a role in adipose lineage specification in mice. ER? regulates adipose progenitor identity and potency, promoting white adipogenic lineage commitment. White adipose progenitors lacking ER? reprogramme and enter into smooth muscle and brown adipogenic fates. Mechanistic studies highlight a TGF? programme involved in progenitor reprogramming downstream of ER? signalling. The observed reprogramming has profound metabolic outcomes; both female and male adipose-lineage ER?-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 ER? cell autonomously regulates adipose lineage commitment, brown fat and smooth muscle cell formation, and systemic metabolism, in a manner relevant to prevalent metabolic diseases.

SUBMITTER: Lapid K 

PROVIDER: S-EPMC4770882 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature