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Publication : Estradiol cycling drives female obesogenic adipocyte hyperplasia.

First Author  Saavedra-Pe?a RDM Year  2023
Journal  Cell Rep Volume  42
Issue  4 Pages  112390
PubMed ID  37053070 Mgi Jnum  J:335243
Mgi Id  MGI:7468523 Doi  10.1016/j.celrep.2023.112390
Citation  Saavedra-Pena RDM, et al. (2023) Estradiol cycling drives female obesogenic adipocyte hyperplasia. Cell Rep 42(4):112390
abstractText  White adipose tissue (WAT) distribution is sex dependent. Adipocyte hyperplasia contributes to WAT distribution in mice driven by cues in the tissue microenvironment, with females displaying hyperplasia in subcutaneous and visceral WAT, while males and ovariectomized females have visceral WAT (VWAT)-specific hyperplasia. However, the mechanism underlying sex-specific hyperplasia remains elusive. Here, transcriptome analysis in female mice shows that high-fat diet (HFD) induces estrogen signaling in adipocyte precursor cells (APCs). Analysis of APCs throughout the estrous cycle demonstrates increased proliferation only when proestrus (high estrogen) coincides with the onset of HFD feeding. We further show that estrogen receptor alpha (ERalpha) is required for this proliferation and that estradiol treatment at the onset of HFD feeding is sufficient to drive it. This estrous influence on APC proliferation leads to increased obesity driven by adipocyte hyperplasia. These data indicate that estrogen drives ERalpha-dependent obesogenic adipocyte hyperplasia in females, exacerbating obesity and contributing to the differential fat distribution between the sexes.
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