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

Kfir Lapid, Ajin Lim, Deborah J. Clegg, Daniel Zeve, Jonathan M. Graff

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Article number5196
JournalNature Communications
Volume5
DOIs
StatePublished - 2014

Fingerprint

estrogens
smooth muscle
muscle cells
fats
muscles
glucose
Smooth Muscle Myocytes
mice
Muscle
metabolic diseases
Cell Differentiation
Estrogens
Stem Cells
Cells
Hot Flashes
diets
phenotype
physiology
Brown Adipose Tissue
Glucose Intolerance

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Oestrogen signalling in white adipose progenitor cells inhibits differentiation into brown adipose and smooth muscle cells. / Lapid, Kfir; Lim, Ajin; Clegg, Deborah J.; Zeve, Daniel; Graff, Jonathan M.

In: Nature Communications, Vol. 5, 5196, 2014.

Research output: Contribution to journalArticle

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