Nuclear hormone-sensitive lipase regulates adipose tissue mass and adipocyte metabolism

In adipocytes, hormone-sensitive lipase (HSL) plays a key role in hydrolyzing triacylglycerols that are stored in lipid droplets. Contrary to the expected phenotype, HSL-deficient mice and humans exhibit lipodystrophy. Here, we show that HSL is also present in the adipocyte nucleus. Mouse models wit...

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Detalles Bibliográficos
Autores: Dufau, Jérémy, Recazens, Emeline, Bottin, Laura, Bergoglio, Camille, Mairal, Aline, Chaoui, Karima, Marques, Marie-Adeline, Jimenez, Veronica|||0000-0001-9145-9877, Garcia, Miquel|||0000-0002-1602-4993, Wang, Tongtong, Laurell, Henrik, Iacovoni, Jason S., Flores-Flores, Remy, Denechaud, Pierre-Damien, Oumar, Khalil Acheikh Ibn, Amri, Ez-Zoubir, Postic, Catherine, Concordet, Jean-Paul, Gourdy, Pierre|||0000-0002-5362-3813, Mejhert, Niklas, Rydén, Mikael, Burlet-Schiltz, Odile, Bosch i Tubert, Fàtima|||0000-0002-7705-5515, Wolfrum, Christian, Mouisel, Etienne, Tavernier, Genevieve, Langin, Dominique
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:321458
Acceso en línea:https://ddd.uab.cat/record/321458
https://dx.doi.org/urn:doi:10.1016/j.cmet.2025.09.014
Access Level:acceso abierto
Palabra clave:Hormone-sensitive lipase
Adipocyte
Adipose tissue
Cell nucleus
Protein-protein interaction
TGF-β signaling
Mitochondrial oxidative phosphorylation
Extracellular matrix
Obesity
Lipodystrophy
Descripción
Sumario:In adipocytes, hormone-sensitive lipase (HSL) plays a key role in hydrolyzing triacylglycerols that are stored in lipid droplets. Contrary to the expected phenotype, HSL-deficient mice and humans exhibit lipodystrophy. Here, we show that HSL is also present in the adipocyte nucleus. Mouse models with different HSL subcellular localizations reveal that nuclear HSL is essential for the maintenance of adipose tissue. Gene silencing in human adipocytes shows that HSL, independently of its enzymatic activity, exerts opposing effects on mitochondrial oxidative phosphorylation and the extracellular matrix. Mechanistically, we found that HSL accumulates in the nucleus by interacting with the transforming growth factor β (TGF-β) signaling mediator, mothers against decapentaplegic homolog 3 (SMAD3). Conversely, HSL phosphorylation induces nuclear export. In vivo, HSL accumulates in the nucleus of adipocytes during high-fat feeding with the converse effect during fasting. Together, our data show that as both a cytosolic enzyme and a nuclear factor, HSL plays a pivotal role in adipocyte biology and adipose tissue maintenance.

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