microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity.
microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity.
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microRNA-33通过增强交感神经活性维持适应性产热。
DOI：
10.1038/s41467-021-21107-5
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发表时间：
2021-02-16
影响因子：
16.6
通讯作者：
Ono K
中科院分区：
文献类型：
--
作者：
Horie T;Nakao T;Miyasaka Y;Nishino T;Matsumura S;Nakazeki F;Ide Y;Kimura M;Tsuji S;Rodriguez RR;Watanabe T;Yamasaki T;Xu S;Otani C;Miyagawa S;Matsushita K;Sowa N;Omori A;Tanaka J;Nishimura C;Nishiga M;Kuwabara Y;Baba O;Watanabe S;Nishi H;Nakashima Y;Picciotto MR;Inoue H;Watanabe D;Nakamura K;Sasaki T;Kimura T;Ono K
适应性产热对生存至关重要，因此受到中枢神经回路的严格调节。在这里，我们表明大脑中的microRNA（miR）-33对于适应性产热是不可或缺的。冷应激增加了下丘脑中的miR-33水平，并且由于交感神经活动减少和棕色脂肪组织（BAT）产热受损，miR-33−/−小鼠无法在寒冷环境中保持体温。对miR-33 f/f多巴胺-β-羟化酶（DBH）-Cre小鼠的分析表明miR-33在Dbh阳性细胞中的重要性。从机制上讲，miR-33缺乏上调γ-氨基丁酸（GABA）A受体亚基基因，如Gabrb 2和Gabra 4。Dbh阳性神经元中这些基因的敲低挽救了miR-33 f/f DBH-Cre小鼠中受损的冷诱导产热。相反，增加小鼠中miR-33的基因剂量会增强产热作用。因此，脑中的miR-33通过抑制GABA能抑制性神经传递，经由增强的交感神经张力，有助于维持BAT产热和全身代谢。这种miR-33介导的神经机制可能是包括冷应激在内的多种应激的生理适应性防御机制。适应性产热受中枢神经回路调节。在这里，作者表明，大脑中的microRNA-33有助于通过增强交感神经张力维持棕色脂肪组织产热和全身能量平衡，并调节GABA a受体亚基的表达。
Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33−/− mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33f/f dopamine-β-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)A receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33f/f DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress. Adaptive thermogenesis is regulated by central neuronal circuits. Here, the authors show that microRNA-33 in the brain contributes to the maintenance of brown adipose tissue thermogenesis and whole-body energy balance via enhanced sympathetic nerve tone, and regulating the expression of GABAa receptor subunits.
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影响因子：
16.6
作者：
Hiraoka, Yoshinori;Matsuoka, Tatsuhiko;Ohno, Mikiko;Nakamura, Kazuhiro;Saijo, Sayaka;Matsumura, Shigenobu;Nishi, Kiyoto;Sakamoto, Jiro;Chen, Po-Min;Inoue, Kazuo;Fushiki, Tohru;Kita, Toru;Kimura, Takeshi;Nishi, Eiichiro
通讯作者：
Nishi, Eiichiro
影响因子：
4.1
作者：
Damiano, Fabrizio;Alemanno, Simone;Siculella, Luisa
通讯作者：
Siculella, Luisa
影响因子：
4.6
作者：
Horie T;Nishino T;Baba O;Kuwabara Y;Nakao T;Nishiga M;Usami S;Izuhara M;Nakazeki F;Ide Y;Koyama S;Sowa N;Yahagi N;Shimano H;Nakamura T;Hasegawa K;Kume N;Yokode M;Kita T;Kimura T;Ono K
通讯作者：
Ono K
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1111/ejn.13966
发表时间：
2018-05-23
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Calarco CA;Li Z;Taylor SR;Lee S;Zhou W;Friedman JM;Mineur YS;Gotti C;Picciotto MR
通讯作者：
Picciotto MR