ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue.
ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue.
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DOI：
10.1016/j.celrep.2021.110003
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发表时间：
2021-11-16
期刊：
影响因子：
8.8
通讯作者：
Yang L
中科院分区：
文献类型：
--
作者：
Sebag SC;Zhang Z;Qian Q;Li M;Zhu Z;Harata M;Li W;Zingman LV;Liu L;Lira VA;Potthoff MJ;Bartelt A;Yang L
棕色脂肪组织（BAT）的产热活性受到细胞氧化还原状态的严格调控，但其潜在的分子机制尚不完全清楚。蛋白质S-亚硝基化是一氧化氮介导的半胱氨酸巯基蛋白质修饰，在细胞氧化还原调节中起重要作用。在这里，我们表明，饮食诱导的肥胖（DIO）和急性寒冷暴露提高BAT蛋白S-亚硝基化，包括UCP 1。这种生热诱导的一氧化氮生物活性受S-亚硝基谷胱甘肽还原酶（GSNOR;乙醇脱氢酶5 [ADH 5]）调节，S-亚硝基谷胱甘肽还原酶是一种平衡细胞内亚硝基氧化还原状态的脱亚硝基酶。BAT中ADH 5的缺失损害了冷诱导的UCP 1依赖性产热和肥胖相关的代谢功能障碍。从机制上讲，我们证明Adh 5的表达是由转录因子热休克因子1（HSF 1）诱导的，给DIO小鼠BAT施用HSF 1激活剂可增加Adh 5的表达，并显著改善UCP 1介导的呼吸。总之，这些数据表明，ADH 5控制BAT亚硝基氧化还原稳态，以调节脂肪产热，这可能是治疗靶向改善代谢健康。Sebag等人报道，ADH 5介导的亚硝基氧化还原稳态调节棕色脂肪产热，HSF 1-Adh 5活化的丧失导致肥胖相关的代谢功能障碍。
Brown adipose tissue (BAT) thermogenic activity is tightly regulated by cellular redox status, but the underlying molecular mechanisms are incompletely understood. Protein S-nitrosylation, the nitric-oxide-mediated cysteine thiol protein modification, plays important roles in cellular redox regulation. Here we show that diet-induced obesity (DIO) and acute cold exposure elevate BAT protein S-nitrosylation, including UCP1. This thermogenic-induced nitric oxide bioactivity is regulated by S-nitrosoglutathione reductase (GSNOR; alcohol dehydrogenase 5 [ADH5]), a denitrosylase that balances the intracellular nitroso-redox status. Loss of ADH5 in BAT impairs cold-induced UCP1-dependent thermogenesis and worsens obesity-associated metabolic dysfunction. Mechanistically, we demonstrate that Adh5 expression is induced by the transcription factor heat shock factor 1 (HSF1), and administration of an HSF1 activator to BAT of DIO mice increases Adh5 expression and significantly improves UCP1-mediated respiration. Together, these data indicate that ADH5 controls BAT nitroso-redox homeostasis to regulate adipose thermogenesis, which may be therapeutically targeted to improve metabolic health. Sebag et al. report that ADH5-mediated nitroso-redox homeostasis regulates brown adipose thermogenesis, and loss of HSF1-Adh5 activation leads to obesity-associated metabolic dysfunction.
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影响因子：
29
作者：
Altshuler-Keylin S;Shinoda K;Hasegawa Y;Ikeda K;Hong H;Kang Q;Yang Y;Perera RM;Debnath J;Kajimura S
通讯作者：
Kajimura S
DOI：
10.1073/pnas.1113319109
发表时间：
2012-03-13
影响因子：
11.1
作者：
Beigi, Farideh;Gonzalez, Daniel R.;Hare, Joshua M.
通讯作者：
Hare, Joshua M.
影响因子：
82.9
作者：
Bartelt A;Widenmaier SB;Schlein C;Johann K;Goncalves RLS;Eguchi K;Fischer AW;Parlakgül G;Snyder NA;Nguyen TB;Bruns OT;Franke D;Bawendi MG;Lynes MD;Leiria LO;Tseng YH;Inouye KE;Arruda AP;Hotamisligil GS
通讯作者：
Hotamisligil GS
DOI：
10.1080/10409238.2017.1304353
发表时间：
2017-06
影响因子：
6.5
作者：
Barnett SD;Buxton ILO
通讯作者：
Buxton ILO
影响因子：
64.8
作者：
Chouchani ET;Kazak L;Jedrychowski MP;Lu GZ;Erickson BK;Szpyt J;Pierce KA;Laznik-Bogoslavski D;Vetrivelan R;Clish CB;Robinson AJ;Gygi SP;Spiegelman BM
通讯作者：
Spiegelman BM