Mouisel Etienne, Bodon Anaïs, Noll Christophe, Cassant-Sourdy Stéphanie, Marques Marie-Adeline, Flores-Flores Remy, Riant Elodie, Bergoglio Camille, Vezin Pierre, Caspar-Bauguil Sylvie, Fournes-Fraresso Camille, Tavernier Geneviève, Oumar Khalil Acheikh Ibn, Gourdy Pierre, Blondin Denis P, Denechaud Pierre-Damien, Carpentier André C, Langin Dominique
Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, Université de Toulouse, Inserm, Université Toulouse III-Paul Sabatier (UPS), Toulouse, France.
Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, Université de Toulouse, Inserm, Université Toulouse III-Paul Sabatier (UPS), Toulouse, France.
Cell Metab. 2025 Feb 4;37(2):429-440.e5. doi: 10.1016/j.cmet.2024.10.018. Epub 2024 Nov 19.
Long-chain fatty acids (FAs) are the major substrates fueling brown adipose tissue (BAT) thermogenesis. Investigation of mouse models has previously called into question the contribution of brown adipocyte intracellular lipolysis to cold-induced non-shivering thermogenesis. Here, we determined the role of the lipolytic enzymes, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in BAT thermogenesis. Brown fat from mice with inducible brown-adipocyte-specific deletion of ATGL and HSL (BAHKO) is hypertrophied with increased lipid droplet size and preserved mitochondria area and density. Maintenance of body temperature during cold exposure is compromised in BAHKO mice in the fasted but not in the fed state. This altered response to cold is observed in various thermal and nutritional conditions. Positron emission tomography-computed tomography using [C]-acetate and [C]-palmitate shows abolished cold-induced BAT oxidative activity and impaired FA metabolism in BAHKO mice. Our findings show that brown adipocyte intracellular lipolysis is required for BAT thermogenesis.
长链脂肪酸（FAs）是为棕色脂肪组织（BAT）产热提供能量的主要底物。此前对小鼠模型的研究对棕色脂肪细胞内脂解作用在冷诱导的非寒战产热中的贡献提出了质疑。在此，我们确定了脂解酶，即脂肪甘油三酯脂肪酶（ATGL）和激素敏感性脂肪酶（HSL）在BAT产热中的作用。可诱导棕色脂肪细胞特异性缺失ATGL和HSL（BAHKO）的小鼠的棕色脂肪肥大，脂滴尺寸增加，线粒体面积和密度得以保留。在禁食状态下，BAHKO小鼠在冷暴露期间维持体温的能力受损，但在进食状态下则不受影响。在各种热和营养条件下均观察到这种对寒冷的反应改变。使用[C] - 醋酸盐和[C] - 棕榈酸盐的正电子发射断层扫描 - 计算机断层扫描显示，BAHKO小鼠中冷诱导的BAT氧化活性消失，脂肪酸代谢受损。我们的研究结果表明，棕色脂肪细胞内脂解作用是BAT产热所必需的。
