An immune-beige adipocyte communication via nicotinic acetylcholine receptor signaling.
An immune-beige adipocyte communication via nicotinic acetylcholine receptor signaling.
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DOI：
10.1038/s41591-018-0032-8
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发表时间：
2018-06
期刊：
影响因子：
82.9
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Jun H;Yu H;Gong J;Jiang J;Qiao X;Perkey E;Kim DI;Emont MP;Zestos AG;Cho JS;Liu J;Kennedy RT;Maillard I;Xu XZS;Wu J
最近，米色脂肪细胞被证明可以在激活时调节能量耗散，并帮助生物体抵御体温过低和肥胖。此前的报告表明，成年人体内存在米色样脂肪细胞，这可能为遏制全球肥胖和代谢疾病的流行提供新的机会。为了鉴定激活的米色脂肪细胞的独特特征，我们发现这些细胞激活期间，皮下脂肪中会诱导胆碱能受体烟碱α2亚基（Chrna2），并且该组织内产生乙酰胆碱的免疫细胞通过旁分泌机制调节该信号通路。 CHRNA2 选择性地在解偶联蛋白 1 (Ucp1)+ 米色脂肪细胞中发挥作用，通过 cAMP 和 PKA 途径增加生热作用。此外，这种通过 CHRNA2 的信号传导是保守的并存在于人类皮下脂肪细胞中。小鼠体内 Chrna2 失活会选择性地损害皮下脂肪中冷诱导的产热反应，并加剧高脂饮食诱导的肥胖和相关代谢紊乱，这表明即使体内米色脂肪调节部分丧失也会导致有害后果。我们的结果揭示了通过 CHRNA2 介导的米色选择性免疫脂肪相互作用，并确定了烟碱乙酰胆碱受体 (nAChR) 在能量代谢中的新功能。这些发现可能有助于确定对抗人类肥胖的治疗靶点。
Beige adipocytes have been recently shown to regulate energy dissipation when activated, and help organisms defend against hypothermia and obesity. Prior reports indicate beige-like adipocytes exist in adult humans and may present novel opportunities to curb the global epidemic in obesity and metabolic illnesses. In an effort to identify unique features of activated beige adipocytes, we uncovered that the cholinergic receptor nicotinic alpha 2 subunit (Chrna2) is induced in subcutaneous fat during the activation of these cells, and that acetylcholine-producing immune cells within this tissue regulate this signaling pathway via paracrine mechanisms. CHRNA2 functions selectively in uncoupling protein 1 (Ucp1)+ beige adipocytes, increasing thermogenesis through a cAMP and PKA pathway. Furthermore, this signaling via CHRNA2 is conserved and present in human subcutaneous adipocytes. Inactivation of Chrna2 in mice compromises the cold-induced thermogenic response selectively in subcutaneous fat and exacerbates high-fat diet-induced obesity and associated metabolic disorders, indicating that even partial loss of beige fat regulation in vivo leads to detrimental consequences. Our results reveal a beige-selective immune-adipose interaction mediated through CHRNA2 and identify a novel function of nicotinic acetylcholine receptors (nAChRs) in energy metabolism. These findings may lead to identification of therapeutic targets to counteract human obesity.
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影响因子：
64.8
作者：
Nguyen, Khoa D.;Qiu, Yifu;Cui, Xiaojin;Goh, Y. P. Sharon;Mwangi, Julia;David, Tovo;Mukundan, Lata;Brombacher, Frank;Locksley, Richard M.;Chawla, Ajay
通讯作者：
Chawla, Ajay
影响因子：
14.8
作者：
Luo, Jinyong;Deng, Zhong-Liang;He, Tong-Chuan
通讯作者：
He, Tong-Chuan
影响因子：
82.9
作者：
Fischer K;Ruiz HH;Jhun K;Finan B;Oberlin DJ;van der Heide V;Kalinovich AV;Petrovic N;Wolf Y;Clemmensen C;Shin AC;Divanovic S;Brombacher F;Glasmacher E;Keipert S;Jastroch M;Nagler J;Schramm KW;Medrikova D;Collden G;Woods SC;Herzig S;Homann D;Jung S;Nedergaard J;Cannon B;Tschöp MH;Müller TD;Buettner C
通讯作者：
Buettner C
影响因子：
29
作者：
Kajimura S;Spiegelman BM;Seale P
通讯作者：
Seale P
DOI：
10.1073/pnas.1221655110
发表时间：
2013-01-22
影响因子：
11.1
作者：
Reardon, Colin;Duncan, Gordon S.;Mak, Tak W.
通讯作者：
Mak, Tak W.