Aryl hydrocarbon receptor-deficient mice are protected from high fat diet-induced changes in metabolic rhythms.
Aryl hydrocarbon receptor-deficient mice are protected from high fat diet-induced changes in metabolic rhythms.
复制标题
DOI：
10.1080/07420528.2016.1256298
复制
发表时间：
2017
影响因子：
2.8
通讯作者：
中科院分区：
文献类型：
--
作者：
高脂肪饮食（HFD）的摄入会改变同步的昼夜节律系统，导致转录振荡出现有害的丧失、增强或偏移。芳香烃受体（AhR）与时钟基因具有结构同源性，包含PAS结构域和碱性螺旋 - 环 - 螺旋结构基序，能够与主要昼夜节律反馈回路的组件相互作用。AhR的激活主要通过抑制Clock/Bmal1介导的Per1调节来改变昼夜节律。AhR缺陷型小鼠可免受饮食诱导的代谢功能障碍，表现出胰岛素敏感性和葡萄糖耐受性增强。本研究探讨了AhR单倍体不足是否也能防止饮食诱导的节律改变。在给AhR +/+和AhR +/-小鼠喂食高脂肪饮食（60%脂肪）15周后，在24小时内每隔4小时收集一次样本。高脂肪饮食改变了野生型C57BL/6J小鼠的血清葡萄糖节律和代谢转录组，包括肝细胞核受体Rev - erba和PPARγ。AhR的减少可防止饮食诱导的转录振荡变化；血清葡萄糖和代谢基因节律免受高脂肪饮食喂养造成的破坏。这些数据强调了AhR信号在代谢调节中的关键作用，并为以节律不同步为特征的疾病提供了一个潜在的治疗靶点。
High fat diet (HFD) consumption alters the synchronized circadian timing system resulting in harmful loss, gain or shift of transcriptional oscillations. The aryl hydrocarbon receptor (AhR) shares structural homology to clock genes, containing both PAS domains and basic helix-loop helix structural motifs, allowing for interaction with components of the primary circadian feedback loop. Activation of AhR alters circadian rhythmicity, primarily through inhibition of Clock/Bmal1-mediated regulation of Per1. AhR-deficient mice are protected from diet-induced metabolic dysfunction, exhibiting enhanced insulin sensitivity and glucose tolerance. This study examined whether AhR haploinsufficiency can also protect against diet-induced alterations in rhythm. After feeding AhR+/+ and AhR+/− mice an HFD (60% fat) for 15 weeks, samples were collected every 4 hours over a 24-hour period. HFD altered the rhythm of serum glucose and the metabolic transcriptome, including hepatic nuclear receptors Rev-erba and PPARy in wild-type c57bl6/j mice. AhR reduction provided protection against diet-induced transcriptional oscillation changes; serum glucose and metabolic gene rhythms were protected from the disruption caused by HFD feeding. These data highlight the critical role of AhR signaling in the regulation of metabolism and provide a potential therapeutic target for diseases characterized by rhythmic desynchrony.
登录
查看更多内容
DOI：
10.1073/pnas.1118726109
发表时间：
2012-04-03
影响因子：
11.1
作者：
Eckel-Mahan, Kristin L.;Patel, Vishal R.;Sassone-Corsi, Paolo
通讯作者：
Sassone-Corsi, Paolo
影响因子：
4.4
作者：
Inoue, I;Shinoda, Y;Katayama, S
通讯作者：
Katayama, S
影响因子：
11.4
作者：
Alessi, DR;Andjelkovic, M;Hemmings, BA
通讯作者：
Hemmings, BA
影响因子：
5.4
作者：
Henriksen, GL;Ketchum, NS;Swaby, JA
通讯作者：
Swaby, JA
影响因子：
5.8
作者：
Gasiewicz, TA;Kende, AS;Willey, JJ
通讯作者：
Willey, JJ