Thermoneutral housing worsens MASLD and reveals defective brown adipose tissue response to β3-adrenergic stimulation
Metabolic dysfunction-associated steatotic liver disease (MASLD), and its more advanced stage metabolic dysfunction-associated steatohepatitis, is the most common chronic liver disease, constituting a major public health issue. Relevant preclinical models are needed to define molecular mechanisms underlying MASLD pathogenesis and evaluate therapeutic approaches. The majority of the lipids accumulating in the liver upon MASLD originate from adipose tissue and appropriate models to study the liver-adipose tissue dialog are also needed. Here, we demonstrated that, compared to standard temperature housing, thermoneutral housing aggravated western diet (WD)-induced obesity, diabetes, and steatosis in male mice, which was associated with increased hepatic expression of inflammation- and fibrosis-related genes. Accordingly, thermoneutral-housed WD-fed mice developed more severe hepatic inflammation and fibrosis compared to standard-housed mice. We next used thermoneutral-housed WD-fed mice to question the effect of MASLD during β3-adrenergic stimulation. We found that diet-induced MASLD is associated with defective inter-organ metabolic cross-talk which leads to impaired activation of brown adipose tissue.
Authors
- Florence Blas-Y-Estrada
- Sandrine Ellero‐Simatos (ORCID: https://orcid.org/0000-0002-9282-1804)
- Anne Fougerat (ORCID: https://orcid.org/0009-0000-0305-1880)
- Étienne Mouisel (ORCID: https://orcid.org/0000-0002-4676-5709)
- Benoît Chassaing (ORCID: https://orcid.org/0000-0002-4285-769X)
- Charlène Dauriat (ORCID: https://orcid.org/0000-0001-7440-6546)
- Laurence Gamet‐Payrastre (ORCID: https://orcid.org/0000-0003-1681-8491)
- Dominique Langin (ORCID: https://orcid.org/0000-0002-2669-7825)
- Justine Bruse
- Frédèric Lasserre (ORCID: https://orcid.org/0000-0001-5220-9787)
- Rémy Florès-Florès (ORCID: https://orcid.org/0009-0007-4053-4954)
- Valentine Melin (ORCID: https://orcid.org/0000-0002-9992-7249)
- Arnaud Polizzi (ORCID: https://orcid.org/0000-0003-1986-2770)
- Sophie Lotersztajn (ORCID: https://orcid.org/0000-0002-0053-7807)
- Justine Bertrand‐Michel (ORCID: https://orcid.org/0000-0001-9815-1517)
- Clémence Rives
- Claire Naylies
- Hervé Rémignon (ORCID: https://orcid.org/0000-0002-4900-0197)
- Yannick Lippi (ORCID: https://orcid.org/0000-0003-4717-078X)
- Thierry Levade (ORCID: https://orcid.org/0000-0003-3793-2584)
- Valérie Alquier‐Bacquie
- Marine Huillet (ORCID: https://orcid.org/0000-0002-6508-4351)
- JingHong Wan (ORCID: https://orcid.org/0000-0002-9274-2460)
- Céline Marie Pauline Martin (ORCID: https://orcid.org/0009-0000-0215-7982)
- Hervé Guillou (ORCID: https://orcid.org/0000-0002-5363-9081)
- Elodie Rousseau-Bacquié (ORCID: https://orcid.org/0000-0002-4580-9036)
- Nicolas Loiseau (ORCID: https://orcid.org/0000-0003-3783-0879)
Institutions
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- École Nationale Vétérinaire de Toulouse (FR)
- Institut Universitaire de France (FR)
- Université Paris Cité (FR)
- Centre Hospitalier Universitaire de Toulouse (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Toxicologie Alimentaire (FR)
- Centre de Recherche sur l'Inflammation (FR)
- Institut des Maladies Métaboliques et Cardiovasculaires (FR)
Publication Details
- Journal
- iScience
- Published
- 2025-07-26
- DOI
- https://doi.org/10.1016/j.isci.2025.113221
- Citations
- 2
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 2.33
Funders
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Région Occitanie Pyrénées-Méditerranée