Serum response factor (SRF) promotes actin cytoskeletal organization in adipocytes to support adaptive hypertrophic expansion and tissue remodeling during obesity in mice
Background - Adipocyte hypertrophy, the unique capacity of adipocytes to enlarge in response to energy surplus, is a crucial determinant of metabolic health during obesity. Nonetheless, the molecular mechanisms governing this adaptive growth remain incompletely characterized. - Methods - Super-enhan...
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| Auteurs principaux: | , , , , , , , , |
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| Format: | Article (Journal) |
| Langue: | anglais |
| Publié: |
May 2026
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| In: |
Metabolism
Year: 2026, Volume: 178, Pages: 1-14 |
| ISSN: | 1532-8600 |
| DOI: | 10.1016/j.metabol.2026.156548 |
| Accès en ligne: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.metabol.2026.156548
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| Notes sur l'auteur: | Jisun So, Jamie Wann, Kyungchan Kim, Solaema Taleb, Hyeong-Geug Kim, Manju Kumari, Alexander S. Banks, X. Charlie Dong, Hyun Cheol Roh |
| Résumé: | Background - Adipocyte hypertrophy, the unique capacity of adipocytes to enlarge in response to energy surplus, is a crucial determinant of metabolic health during obesity. Nonetheless, the molecular mechanisms governing this adaptive growth remain incompletely characterized. - Methods - Super-enhancer landscapes in adipocytes were mapped via H3K27ac chromatin immunoprecipitation sequencing analysis of adipocyte nuclei from mice fed either a standard chow diet or high-fat diet (HFD) to identify transcriptional regulators activated under obesogenic conditions. Functional validation was conducted through both in vitro and in vivo experiments, including adipocyte-specific gene deletion mouse models, followed by single-nucleus RNA sequencing. - Results - Super-enhancer profiling identified Serum Response Factor (SRF) as a critical driver of actin cytoskeletal remodeling in adipocytes during obesity. SRF was shown to be both necessary and sufficient for regulation of actin cytoskeletal gene expression in 3T3-L1 adipocytes. Adipocyte-specific SRF ablation in mice led to reduced expression of actin cytoskeletal genes, disruption of actin filament organization, and impaired adipocyte enlargement under HFD feeding. Despite comparable body weight, SRF-deficient mice developed exacerbated insulin resistance and ectopic lipid accumulation in the liver and brown adipose tissue, indicative of compromised lipid storage within adipocytes. Single-nucleus RNA-seq further revealed that cell-intrinsic actin cytoskeletal defects in adipocytes propagated to tissue-level dysfunction, impairing vascularization and increasing inflammation. - Conclusion - These findings establish SRF as a central regulator of actin cytoskeletal organization that promotes healthy adipocyte hypertrophy and adipose tissue remodeling. Enhancing SRF-dependent cytoskeletal remodeling in adipocytes may offer a therapeutic strategy to preserve metabolic health in obesity. |
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| Description: | Gesehen am 24.06.2026 |
| Description matérielle: | Online Resource |
| ISSN: | 1532-8600 |
| DOI: | 10.1016/j.metabol.2026.156548 |