Summary
This thesis demonstrates that selective depletion of gram-positive gut bacteria disrupts hepatic circadian rhythm by altering core clock gene expression, proteins, and circadian-regulated metabolites in mice. Conversely, deletion of all three hepatic PPARs (α, β, γ) did not significantly alter liver circadian core clock or target gene expression, suggesting PPARs are not essential drivers of the liver peripheral clock.
Key Findings
- Antibiotic-induced elimination of gram-positive bacteria perturbed hepatic core clock gene expression and altered circadian-regulated proteins and metabolites in C57BL/6 mice.
- Gut microbiota may protect against pharmacological circadian disruption induced by the antibiotic metronidazole.
- Hepatocyte-specific triple deletion of Pparα, Pparβ, and Pparγ showed no significant alteration in liver circadian core clock genes or circadian target genes by qPCR and RNAseq analysis.
- Gram-positive bacteria manipulation was identified as a potential therapeutic target to suppress liver cancer via a possible link to liver cell proliferation.
Categories
Sleep & Circadian Health: Investigates how gut microbiota composition and hepatic PPARs regulate peripheral circadian clock gene expression in the liver.
Author(s)
PHY Oh
Publication Year
2018
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