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.

中文翻译：

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冷诱导的生热依赖于心肌中ATGL介导的脂解作用，而不是棕色脂肪组织

脂肪酸（FAs）激活并促进棕色脂肪组织（BAT）中UCP1介导的非颤抖生热（NST）。脂肪甘油三酯脂肪酶（ATGL）从细胞内脂肪储存中释放FAs被认为是NST的关键步骤。因此，全球性ATGL基因敲除（AKO）小鼠的严重寒冷耐受性已归因于BAT脂解缺陷。这里我们证明这个结论是不正确的。我们证明，尽管ATGL的BAT特异性丧失会损害BAT脂解作用并改变BAT形态，但它不会损害β3-肾上腺素热原性反应或冷诱导的NST。相反，NST取决于禁食期间白色脂肪组织中的营养供应或脂解作用，这表明循环的能量底物足以为NST提供燃料。AKO小鼠的耐冷性不是由先前怀疑的BAT功能障碍引起的，而是由严重的心肌病引起的。我们得出结论，功能性NST需要充足的底物供应和心脏功能，但不依赖于BAT中ATGL介导的脂解作用。