Thermogenic adipocyte-derived zinc promotes sympathetic innervation in male mice
Thermogenic adipocyte-derived zinc promotes sympathetic innervation in male mice
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DOI：
10.1038/s42255-023-00751-9
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发表时间：
2023-03-06
影响因子：
20.8
通讯作者：
Luan，Bing
中科院分区：
文献类型：
--
作者：
Jiang，Junkun;Zhou，Donglei;Luan，Bing
交感神经元通过释放儿茶酚胺来激活生热脂肪细胞；然而，生热脂肪细胞对交感神经支配的调节尚不清楚。在这里，我们确定初级锌离子(锌)是一种生热脂肪细胞分泌的因子，它促进雄性小鼠棕色脂肪组织和皮下白色脂肪组织的交感神经支配和生热。耗尽生热脂肪细胞或拮抗脂肪细胞上的β3-肾上腺素能受体会损害交感神经支配。在肥胖中，炎症诱导的锌伴侣蛋白金属硫蛋白-2的上调减少了产热脂肪细胞的锌分泌，导致能量消耗减少。此外，补充锌通过促进交感神经诱导的产热来缓解肥胖，而去交感神经则取消了这一抗肥胖作用。因此，我们已经确定了生热脂肪细胞和交感神经元的相互调节的正反馈机制。这一机制对适应性产热很重要，可能成为治疗肥胖的潜在靶点。
Sympathetic neurons activate thermogenic adipocytes through release of catecholamine; however, the regulation of sympathetic innervation by thermogenic adipocytes is unclear. Here, we identify primary zinc ion (Zn) as a thermogenic adipocyte-secreted factor that promotes sympathetic innervation and thermogenesis in brown adipose tissue and subcutaneous white adipose tissue in male mice. Depleting thermogenic adipocytes or antagonizing β3-adrenergic receptor on adipocytes impairs sympathetic innervation. In obesity, inflammation-induced upregulation of Zn chaperone protein metallothionein-2 decreases Zn secretion from thermogenic adipocytes and leads to decreased energy expenditure. Furthermore, Zn supplementation ameliorates obesity by promoting sympathetic neuron-induced thermogenesis, while sympathetic denervation abrogates this antiobesity effect. Thus, we have identified a positive feedback mechanism for the reciprocal regulation of thermogenic adipocytes and sympathetic neurons. This mechanism is important for adaptive thermogenesis and could serve as a potential target for the treatment of obesity.