Metronidazole Causes Skeletal Muscle Atrophy and Modulates Muscle Chronometabolism.

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State: Public
Version: Final published version
Serval ID
serval:BIB_F33011C1E55D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Metronidazole Causes Skeletal Muscle Atrophy and Modulates Muscle Chronometabolism.
Journal
International journal of molecular sciences
Author(s)
Manickam R., Oh HYP, Tan C.K., Paramalingam E., Wahli W.
ISSN
1422-0067 (Electronic)
ISSN-L
1422-0067
Publication state
Published
Issued date
16/08/2018
Peer-reviewed
Oui
Volume
19
Number
8
Pages
E2418
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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 <i>Proteobacteria</i> 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 <i>Hdac4</i> , <i>myogenin</i> , <i>MuRF1</i> , and <i>atrogin1</i> , which are implicated in skeletal muscle neurogenic atrophy. Metronidazole in SPF mice also upregulates skeletal muscle <i>FoxO3</i> , 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 <i>Cry2</i> , <i>Ror</i> - <i>β</i> , and <i>E4BP4</i> . <i>PPARγ</i> and one of its important target genes, <i>adiponectin</i> , are also upregulated by metronidazole. Metronidazole in germ-free (GF) mice increases the expression of other core clock genes, such as <i>Bmal1</i> and <i>Per2</i> , as well as the metabolic regulators <i>FoxO1</i> and <i>Pdk4</i> , 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.
Keywords
Adenosine/analogs & derivatives, Adenosine/metabolism, Adiponectin/genetics, Adiponectin/metabolism, Animals, CLOCK Proteins/genetics, CLOCK Proteins/metabolism, Colony Count, Microbial, Energy Metabolism/drug effects, Epigenesis, Genetic/drug effects, Metronidazole/pharmacology, Metronidazole/therapeutic use, Mice, Inbred C57BL, Muscle, Skeletal/drug effects, Muscle, Skeletal/metabolism, Muscle, Skeletal/pathology, Muscular Atrophy/drug therapy, Muscular Atrophy/metabolism, Organ Size, PPAR gamma/genetics, PPAR gamma/metabolism, Proteobacteria/drug effects, Proteobacteria/growth & development, RNA/metabolism, circadian rhythm, gut dysbiosis, metronidazole, skeletal muscle atrophy
Pubmed
Web of science
Open Access
Yes
Create date
31/08/2018 11:14
Last modification date
20/08/2019 16:20
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