Estradiol cycling drives female obesogenic adipocyte hyperplasia
Summary: 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 W...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723004011 |
| _version_ | 1797847298449866752 |
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| author | Rocío del M. Saavedra-Peña Natalia Taylor Clare Flannery Matthew S. Rodeheffer |
| author_facet | Rocío del M. Saavedra-Peña Natalia Taylor Clare Flannery Matthew S. Rodeheffer |
| author_sort | Rocío del M. Saavedra-Peña |
| collection | DOAJ |
| description | Summary: 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 α (ERα) 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 ERα-dependent obesogenic adipocyte hyperplasia in females, exacerbating obesity and contributing to the differential fat distribution between the sexes. |
| first_indexed | 2024-04-09T18:09:03Z |
| format | Article |
| id | doaj.art-77bd1ad6c0034868a67813e4d7f459f3 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-09T18:09:03Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-77bd1ad6c0034868a67813e4d7f459f32023-04-14T04:19:06ZengElsevierCell Reports2211-12472023-04-01424112390Estradiol cycling drives female obesogenic adipocyte hyperplasiaRocío del M. Saavedra-Peña0Natalia Taylor1Clare Flannery2Matthew S. Rodeheffer3Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USADepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USADepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University, New Haven, CT 06520, USA; Section of Endocrinology and Metabolism, Yale University, New Haven, CT 06520, USADepartment of Comparative Medicine, Yale University, New Haven, CT 06520, USA; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA; Yale Center for Molecular and Systems Metabolism, Yale University, New Haven, CT 06520, USA; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06520, USA; Corresponding authorSummary: 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 α (ERα) 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 ERα-dependent obesogenic adipocyte hyperplasia in females, exacerbating obesity and contributing to the differential fat distribution between the sexes.http://www.sciencedirect.com/science/article/pii/S2211124723004011CP: Metabolism |
| spellingShingle | Rocío del M. Saavedra-Peña Natalia Taylor Clare Flannery Matthew S. Rodeheffer Estradiol cycling drives female obesogenic adipocyte hyperplasia Cell Reports CP: Metabolism |
| title | Estradiol cycling drives female obesogenic adipocyte hyperplasia |
| title_full | Estradiol cycling drives female obesogenic adipocyte hyperplasia |
| title_fullStr | Estradiol cycling drives female obesogenic adipocyte hyperplasia |
| title_full_unstemmed | Estradiol cycling drives female obesogenic adipocyte hyperplasia |
| title_short | Estradiol cycling drives female obesogenic adipocyte hyperplasia |
| title_sort | estradiol cycling drives female obesogenic adipocyte hyperplasia |
| topic | CP: Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723004011 |
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