法国图卢兹第三大学Dominique Langin研究小组近日取得一项新成果。他们的最新研究揭示了冷诱导产热需要中性脂肪酶介导的棕色脂肪细胞内脂解。相关论文于2024年11月19日发表在《细胞—代谢》杂志上。

研究人员表示，长链脂肪酸（FAs）是棕色脂肪组织（BAT）产热的主要底物。对motheme模型的研究先前质疑了，棕色脂肪细胞内脂肪分解对冷诱导的非寒战产热的贡献。

该研究团队确定了脂溶酶、脂肪甘油三酯脂肪酶（ATGL）和激素敏感脂肪酶（HSL）在BAT产热中的作用。诱导褐色脂肪细胞特异性缺失ATGL和HSL （BAHKO）小鼠的褐色脂肪增厚，脂滴大小增加，线粒体面积和密度保持不变。

在寒冷暴露期间，BAHKO小鼠在禁食状态下的体温维持受到损害，而在喂食状态下则没有。在不同的热和营养条件下观察到这种对寒冷的改变反应。

正电子发射断层扫描-计算机断层扫描显示，在BAHKO小鼠中，冷诱导的BAT氧化活性被消除，FA代谢受损。他们的发现表明棕色脂肪细胞胞内脂解是BAT产热所必需的。

附：英文原文

Title: Cold-induced thermogenesis requires neutral-lipase-mediated intracellular lipolysis in brown adipocytes

Author: Etienne Mouisel, Anas Bodon, Christophe Noll, Stéphanie Cassant-Sourdy, Marie-Adeline Marques, Remy Flores-Flores, Elodie Riant, Camille Bergoglio, Pierre Vezin, Sylvie Caspar-Bauguil, Camille Fournes-Fraresso, Geneviève Tavernier, Khalil Acheikh Ibn Oumar, Pierre Gourdy, Denis P. Blondin, Pierre-Damien Denechaud, André C. Carpentier, Dominique Langin

Issue&Volume: 2024-11-19

Abstract: 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 [11C]-acetate and [11C]-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.

DOI: 10.1016/j.cmet.2024.10.018

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00414-5