Conditional deletion of Hdac3 in osteoprogenitor cells attenuates diet-induced systemic metabolic dysfunction.
Conditional deletion of Hdac3 in osteoprogenitor cells attenuates diet-induced systemic metabolic dysfunction.
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DOI：
10.1016/j.mce.2015.02.001
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发表时间：
2015-07-15
影响因子：
4.1
通讯作者：
Westendorf, Jennifer J.
中科院分区：
文献类型：
--
作者：
McGee-Lawrence, Meghan E.;White, Thomas A.;LeBrasseur, Nathan K.;Westendorf, Jennifer J.
肥胖是美国的一种主要健康流行病，也是包括2型糖尿病在内的可预防疾病的主要原因。越来越多的证据表明，骨骼影响全身代谢，并提出了一个新的途径，开发新的治疗药物，但其潜在的机制还没有得到很好的理解。在这里，它表明，条件删除表观遗传调节，Hdac3，在成骨细胞祖细胞废除高脂肪饮食诱导的胰岛素抵抗和肝脂肪变性。这些Hdac3缺陷小鼠具有减少的骨形成和较低的循环水平的总和低羧基化骨钙蛋白，再加上降低的骨吸收活性。他们还保持较低的身体脂肪和空腹血糖水平的正常和高脂肪的食物饮食。Hdac 3从成骨细胞内控制系统能量稳态的机制尚未完全实现，但目前的研究表明，它不涉及循环骨钙素水平的升高。因此，Hdac 3是骨骼影响全身能量代谢的新兴范式中的新参与者。
Obesity is a major health epidemic in the United States and a leading cause of preventable diseases including type 2 diabetes. A growing body of evidence indicates that the skeleton influences whole body metabolism and suggests a new avenue for developing novel therapeutic agents, but the underlying mechanisms are not well understood. Here, it is demonstrated that conditional deletion of an epigenetic regulator, Hdac3, in osteoblast progenitor cells abrogates high fat diet-induced insulin resistance and hepatic steatosis. These Hdac3-deficient mice have reduced bone formation and lower circulating levels of total and undercarboxylated osteocalcin, coupled with decreased bone resorption activity. They also maintain lower body fat and fasting glucose levels on normal and high fat chow diets. The mechanisms by which Hdac3 controls systemic energy homeostasis from within osteoblasts have not yet been fully realized, but the current study suggests that it does not involve elevated levels of circulating osteocalcin. Thus, Hdac3 is a new player in the emerging paradigm that the skeleton influences systemic energy metabolism.
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影响因子：
64.8
作者：
Alenghat, Theresa;Meyers, Katherine;Mullican, Shannon E.;Leitner, Kirstin;Adeniji-Adele, Adetoun;Avila, Jacqueline;Bucan, Maja;Ahima, Rexford S.;Kaestner, Klaus H.;Lazar, Mitchell A.
通讯作者：
Lazar, Mitchell A.
影响因子：
64.5
作者：
Ferron M;Wei J;Yoshizawa T;Del Fattore A;DePinho RA;Teti A;Ducy P;Karsenty G
通讯作者：
Karsenty G
影响因子：
5.9
作者：
Akbaraly, Tasnime;Sabia, Severine;Hagger-Johnson, Gareth;Tabak, Adam G.;Shipley, Martin J.;Jokela, Markus;Brunner, Eric J.;Hamer, Mark;Batty, G. David;Singh-Manoux, Archana;Kivimaki, Mika
通讯作者：
Kivimaki, Mika
影响因子：
16.2
作者：
Esposito K;Chiodini P;Colao A;Lenzi A;Giugliano D
通讯作者：
Giugliano D
影响因子：
3.7
作者：
Razidlo DF;Whitney TJ;Casper ME;McGee-Lawrence ME;Stensgard BA;Li X;Secreto FJ;Knutson SK;Hiebert SW;Westendorf JJ
通讯作者：
Westendorf JJ