HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning.
HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning.
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DOI：
10.1038/s41467-017-00182-7
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发表时间：
2017-07-21
影响因子：
16.6
通讯作者：
Crestani M
中科院分区：
文献类型：
--
作者：
Ferrari A;Longo R;Fiorino E;Silva R;Mitro N;Cermenati G;Gilardi F;Desvergne B;Andolfo A;Magagnotti C;Caruso D;Fabiani E;Hiebert SW;Crestani M
白色脂肪组织（WAT）可响应于环境刺激（例如寒冷）而经历表型转换，称为布朗宁。组蛋白的翻译后修饰已被证明可以调节细胞能量代谢，但它们在白色脂肪组织生理学中的作用仍不完全清楚。在这里，我们表明，组蛋白去乙酰化酶3（HDAC 3）调节WAT代谢和功能。脂肪中Hdac 3的选择性消融通过激活从头脂肪酸合成和β-氧化的无效循环来转换WAT的代谢特征，所述无效循环增强WAT氧化能力并最终支持布朗宁。脂肪组织中Hdac 3的特异性消融增加了Pparg和Ucp 1基因中增强子的乙酰化，以及Ppara基因的推定调控区的乙酰化。我们的研究结果揭示了HDAC 3作为WAT生理学的调节剂，其作为抑制脂肪酸代谢和WAT布朗宁的分子制动器。组蛋白脱乙酰酶，如HDAC 3，已显示改变各种组织中的细胞代谢。在这里，作者表明HDAC 3通过激活脂肪酸合成和氧化的无效循环来调节WAT代谢，这支持WAT布朗宁。
White adipose tissue (WAT) can undergo a phenotypic switch, known as browning, in response to environmental stimuli such as cold. Post-translational modifications of histones have been shown to regulate cellular energy metabolism, but their role in white adipose tissue physiology remains incompletely understood. Here we show that histone deacetylase 3 (HDAC3) regulates WAT metabolism and function. Selective ablation of Hdac3 in fat switches the metabolic signature of WAT by activating a futile cycle of de novo fatty acid synthesis and β-oxidation that potentiates WAT oxidative capacity and ultimately supports browning. Specific ablation of Hdac3 in adipose tissue increases acetylation of enhancers in Pparg and Ucp1 genes, and of putative regulatory regions of the Ppara gene. Our results unveil HDAC3 as a regulator of WAT physiology, which acts as a molecular brake that inhibits fatty acid metabolism and WAT browning. Histone deacetylases, such as HDAC3, have been shown to alter cellular metabolism in various tissues. Here the authors show that HDAC3 regulates WAT metabolism by activating a futile cycle of fatty acid synthesis and oxidation, which supports WAT browning.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
16.6
作者：
Abe, Yohei;Rozqie, Royhan;Matsumura, Yoshihiro;Kawamura, Takeshi;Nakaki, Ryo;Tsurutani, Yuya;Tanimura-Inagaki, Kyoko;Shiono, Akira;Magoori, Kenta;Nakamura, Kanako;Ogi, Shotaro;Kajimura, Shingo;Kimura, Hiroshi;Tanaka, Toshiya;Fukami, Kiyoko;Osborne, Timothy F.;Kodama, Tatsuhiko;Aburatani, Hiroyuki;Inagaki, Takeshi;Sakai, Juro
通讯作者：
Sakai, Juro
DOI：
10.1126/science.1198125
发表时间：
2011-03-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Feng D;Liu T;Sun Z;Bugge A;Mullican SE;Alenghat T;Liu XS;Lazar MA
通讯作者：
Lazar MA
影响因子：
4.8
作者：
Armoni, M;Kritz, N;Karnieli, E
通讯作者：
Karnieli, E
DOI：
10.1152/ajpendo.00271.2013
发表时间：
2014-08-01
影响因子：
5.1
作者：
Cummins, Timothy D.;Holden, Candice R.;Hill, Bradford G.
通讯作者：
Hill, Bradford G.