图卢兹大学Dominique Langin研究组揭示了核激素敏感脂肪酶调节脂肪组织质量和脂肪细胞代谢。这一研究成果于2025年10月23日发表在国际顶尖学术期刊《细胞—代谢》上。

该课题组人员发现HSL也存在于脂肪细胞核中。具有不同HSL亚细胞定位的Motheme模型表明，核HSL对脂肪组织的维持至关重要。人脂肪细胞中的基因沉默表明，HSL独立于其酶活性，对线粒体氧化磷酸化和细胞外基质产生相反的作用。在机制上，研究组发现HSL通过与转化生长因子β (TGF-β)信号介质母体抗十足瘫痪同源物3 （SMAD3）相互作用在核中积累。相反，HSL磷酸化诱导核输出。在体内，高脂肪喂养期间，HSL在脂肪细胞核中积累，而禁食期间则相反。总之，他们的数据表明，作为一种细胞质酶和核因子，HSL在脂肪细胞生物学和脂肪组织维持中起着关键作用。

据了解，在脂肪细胞中，激素敏感脂肪酶（HSL）在水解储存在脂滴中的三酰基甘油中起关键作用。与预期的表型相反，HSL缺陷小鼠和人类表现出脂肪营养不良。

附：英文原文

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

Author: Jérémy Dufau, Emeline Recazens, Laura Bottin, Camille Bergoglio, Aline Mairal, Karima Chaoui, Marie-Adeline Marques, Veronica Jimenez, Miquel García, Tongtong Wang, Henrik Laurell, Jason S. Iacovoni, Remy Flores-Flores, Pierre-Damien Denechaud, Khalil Acheikh Ibn Oumar, Ez-Zoubir Amri, Catherine Postic, Jean-Paul Concordet, Pierre Gourdy, Niklas Mejhert, Mikael Rydén, Odile Burlet-Schiltz, Fatima Bosch, Christian Wolfrum, Etienne Mouisel, Genevieve Tavernier, Dominique Langin

Issue&Volume: 2025-10-23

Abstract: 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.

DOI: 10.1016/j.cmet.2025.09.014

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00433-4