Cold-Induced Thermogenesis Depends on ATGL-Mediated Lipolysis in Cardiac Muscle, but Not Brown Adipose Tissue.
Cold-Induced Thermogenesis Depends on ATGL-Mediated Lipolysis in Cardiac Muscle, but Not Brown Adipose Tissue.
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DOI：
10.1016/j.cmet.2017.09.004
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发表时间：
2017-11-07
期刊：
影响因子：
29
通讯作者：
Zechner R
中科院分区：
文献类型：
--
作者：
Schreiber R;Diwoky C;Schoiswohl G;Feiler U;Wongsiriroj N;Abdellatif M;Kolb D;Hoeks J;Kershaw EE;Sedej S;Schrauwen P;Haemmerle G;Zechner R
脂肪酸（FA）激活和燃料UCP 1介导的非颤抖性产热（NST）在棕色脂肪组织（BAT）。脂肪甘油三酯脂肪酶（ATGL）从细胞内脂肪库中释放脂肪酸被认为是NST的关键步骤。因此，全球ATGL敲除（AKO）小鼠的严重的冷不耐受性归因于缺陷的BAT脂解。在这里，我们证明这个结论是不正确的。我们证明，虽然BAT特异性ATGL的丢失损害BAT脂解并改变BAT形态，但它不会损害β3-肾上腺素能产热反应或冷诱导的NST。相反，NST依赖于禁食期间白色脂肪组织中的营养供应或脂解，表明循环能量底物足以为NST提供燃料。AKO小鼠的冷耐受不良不是由BAT功能障碍引起的，而是由严重的心肌病引起的。我们的结论是，功能NST需要足够的底物供应和心脏功能，但不依赖于ATGL介导的脂肪分解BAT。BAT中的ATGL不是体内冷诱导产热的先决条件WAT中的ATGL对于在禁食期间释放脂肪酸用于能量燃烧至关重要心脏中ATGL的丧失由于心脏储备不足而诱导体温过低在BAT中缺乏ATGL的小鼠中适应性产热是正常的Schreiber et al.证明了ATGL介导的棕色脂肪组织中的脂解不是体内冷诱导的非颤抖性产热的先决条件。相反，白色脂肪组织和心脏中的ATGL分别对于在禁食期间供应脂肪酸和满足寒冷中对心血管系统增加的需求至关重要。
Fatty acids (FAs) activate and fuel UCP1-mediated non-shivering thermogenesis (NST) in brown adipose tissue (BAT). Release of FAs from intracellular fat stores by adipose triglyceride lipase (ATGL) is considered a key step in NST. Accordingly, the severe cold intolerance of global ATGL knockout (AKO) mice has been attributed to defective BAT lipolysis. Here we show that this conclusion is incorrect. We demonstrate that although the BAT-specific loss of ATGL impairs BAT lipolysis and alters BAT morphology, it does not compromise the β3-adrenergic thermogenic response or cold-induced NST. Instead, NST depends on nutrient supply or lipolysis in white adipose tissue during fasting, suggesting that circulating energy substrates are sufficient to fuel NST. Cold intolerance in AKO mice is not caused by BAT dysfunction as previously suspected but by severe cardiomyopathy. We conclude that functional NST requires adequate substrate supply and cardiac function, but does not depend on ATGL-mediated lipolysis in BAT. ATGL in BAT is not a prerequisite for cold-induced thermogenesis in vivo ATGL in WAT is crucial to liberate fatty acids for energy combustion during fasting Loss of ATGL in the heart induces hypothermia due to insufficient cardiac reserve Adaptive thermogenesis is normal in mice lacking ATGL in BAT Schreiber et al. demonstrate that ATGL-mediated lipolysis in brown adipose tissue is not a prerequisite for cold-induced non-shivering thermogenesis in vivo. Instead, ATGL in white adipose tissue and the heart is essential for supplying fatty acids during fasting and for meeting increased demands on the cardiovascular system in the cold, respectively.
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