Metronidazole Causes Skeletal Muscle Atrophy and Modulates Muscle Chronometabolism.
Metronidazole Causes Skeletal Muscle Atrophy and Modulates Muscle Chronometabolism.
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DOI：
10.3390/ijms19082418
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发表时间：
2018-08-16
影响因子：
5.6
通讯作者：
Wahli W
中科院分区：
文献类型：
--
作者：
Manickam R;Oh HYP;Tan CK;Paramalingam E;Wahli W
抗生素导致对病原生物定殖的易感性增加，对宿主-微生物群关系具有不同的影响。在这里，我们表明，甲硝唑治疗的特定病原体（SPF）小鼠的结果在显着增加的细菌门变形菌在粪便颗粒。此外，甲硝哒唑在SPF小鼠中降低后肢肌肉重量，并导致胫骨前肌中的纤维变小。在腓肠肌中，甲硝唑引起Hdac 4、肌细胞生成素、MuRF 1和atrogin 1的上调，这与骨骼肌神经源性萎缩有关。甲硝唑在SPF小鼠也上调骨骼肌FoxO 3，被描述为参与细胞凋亡和肌肉再生。值得注意的是，肠道微生物群的改变导致肌肉核心时钟和效应基因Cry 2、Ror-β和E4 BP 4的表达增加。PPARγ及其重要靶基因之一脂联素也被甲硝唑上调。甲硝唑在无菌（GF）小鼠中增加了其他核心时钟基因的表达，如Bmal 1和Per 2，以及代谢调节因子FoxO 1和Pdk 4，这表明了一种不依赖于微生物群的药理作用。总之，甲硝唑在SPF小鼠中导致骨骼肌萎缩，并改变参与肌肉外周昼夜节律机制和代谢调节的基因表达。
Antibiotics lead to increased susceptibility to colonization by pathogenic organisms, with different effects on the host-microbiota relationship. Here, we show that metronidazole treatment of specific pathogen-free (SPF) mice results in a significant increase of the bacterial phylum Proteobacteria in fecal pellets. Furthermore, metronidazole in SPF mice decreases hind limb muscle weight and results in smaller fibers in the tibialis anterior muscle. In the gastrocnemius muscle, metronidazole causes upregulation of Hdac4, myogenin, MuRF1, and atrogin1, which are implicated in skeletal muscle neurogenic atrophy. Metronidazole in SPF mice also upregulates skeletal muscle FoxO3, described as involved in apoptosis and muscle regeneration. Of note, alteration of the gut microbiota results in increased expression of the muscle core clock and effector genes Cry2, Ror-β, and E4BP4. PPARγ and one of its important target genes, adiponectin, are also upregulated by metronidazole. Metronidazole in germ-free (GF) mice increases the expression of other core clock genes, such as Bmal1 and Per2, as well as the metabolic regulators FoxO1 and Pdk4, suggesting a microbiota-independent pharmacologic effect. In conclusion, metronidazole in SPF mice results in skeletal muscle atrophy and changes the expression of genes involved in the muscle peripheral circadian rhythm machinery and metabolic regulation.
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影响因子：
8.1
作者：
Dyar KA;Ciciliot S;Wright LE;Biensø RS;Tagliazucchi GM;Patel VR;Forcato M;Paz MI;Gudiksen A;Solagna F;Albiero M;Moretti I;Eckel-Mahan KL;Baldi P;Sassone-Corsi P;Rizzuto R;Bicciato S;Pilegaard H;Blaauw B;Schiaffino S
通讯作者：
Schiaffino S
DOI：
10.1073/pnas.1014523107
发表时间：
2010-11-02
影响因子：
11.1
作者：
Andrews, Jessica L.;Zhang, Xiping;Esser, Karyn A.
通讯作者：
Esser, Karyn A.
影响因子：
15.9
作者：
Fujisaka, Shiho;Ussar, Siegfried;Kahn, C. Ronald
通讯作者：
Kahn, C. Ronald
影响因子：
6.9
作者：
Barnea, Maayan;Madar, Zecharia;Froy, Oren
通讯作者：
Froy, Oren
影响因子：
4.2
作者：
Chun J;Kim KY;Lee JH;Choi Y
通讯作者：
Choi Y