NCOA1 is a gatekeeper of the sexually dimorphic thermogenic activity of white adipose tissue
Premenopausal women preferentially store fat in subcutaneous depots, which provides protection against cardiometabolic disease. Their white adipose tissue also exhibits a more thermogenic, brown-like profile compared with that of men, yet the mechanisms underlying this sex-specific benefit remain unclear. Here, we show that Nuclear Receptor Coactivator 1 is highly expressed in human subcutaneous fat, with further induction during the conversion of white to beige adipocytes and in response to caloric restriction. Loss of Nuclear Receptor Coactivator 1 in subcutaneous adipocytes revealed a cell-autonomous role in promoting beiging by directly regulating the thermogenic factor Uncoupling Protein 1 and sex-dependent mitochondrial gene networks activated by cold and adrenergic stimulation. Acting together with GATA binding protein 3, it establishes elevated basal thermogenic tone in female subcutaneous fat. Female mice lacking this coregulator progressively developed obesity and glucose intolerance, and a male-like fat distribution, with increased visceral fat and reduced beige adipocytes. These findings identify Nuclear Receptor Coactivator 1 as a sex-specific determinant of adipose tissue remodelling and female metabolic resilience.
Authors
- Hichem Bouguerra
- Jean‐François Tanti (ORCID: https://orcid.org/0000-0003-1782-1318)
- Anne Bouloumié
- Dominique Langin (ORCID: https://orcid.org/0000-0002-2669-7825)
- Noura Lamghari
- Émilie Montastier (ORCID: https://orcid.org/0000-0002-7303-3837)
- Élodie Riant
- Didier F. Pisani (ORCID: https://orcid.org/0000-0001-5879-8527)
- Viguerie Nathalie
- Nadine Gautier
- Marine Bourcier
- Jean-François Louet
- Mounia Tannour-Louet
- Ez-Zoubir Amri
- Mireille Cormont
- Benoit Chaput
- Alycia Zedda
- Pierre Gourdy
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Institut Universitaire de France (FR)
- Institut de Chimie de Nice (FR)
- Institut de Biologie Valrose (FR)
- Centre Méditerranéen de Médecine Moléculaire (FR)
- Observatoire de la Côte d’Azur (FR)
- Institut des Maladies Métaboliques et Cardiovasculaires (FR)
- Institut de Physique de Nice (FR)
- Institut de Pharmacologie Moléculaire et Cellulaire (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-01-20
- DOI
- https://doi.org/10.1038/s41467-025-65229-6
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- Institut National Du Cancer
- Centre Hospitalier Universitaire de Toulouse
- Société Francophone du Diabète