PMID- 37122023
OWN - NLM
STAT- MEDLINE
DCOM- 20230502
LR  - 20240404
IS  - 1474-760X (Electronic)
IS  - 1474-7596 (Print)
IS  - 1474-7596 (Linking)
VI  - 24
IP  - 1
DP  - 2023 Apr 30
TI  - Caloric restriction remodels the hepatic chromatin landscape and bile acid 
      metabolism by modulating the gut microbiota.
PG  - 98
LID - 10.1186/s13059-023-02938-5 [doi]
LID - 98
AB  - BACKGROUND: Caloric restriction (CR) has been known to promote health by 
      reprogramming metabolism, yet little is known about how the epigenome and 
      microbiome respond during metabolic adaptation to CR. RESULTS: We investigate 
      chromatin modifications, gene expression, as well as alterations in microbiota in 
      a CR mouse model. Collectively, short-term CR leads to altered gut microbial 
      diversity and bile acid metabolism, improving energy expenditure. CR remodels the 
      hepatic enhancer landscape at genomic loci that are enriched for binding sites 
      for signal-responsive transcription factors, including HNF4alpha. These alterations 
      reflect a dramatic reprogramming of the liver transcriptional network, including 
      genes involved in bile acid metabolism. Transferring CR gut microbiota into mice 
      fed with an obesogenic diet recapitulates the features of CR-related bile acid 
      metabolism along with attenuated fatty liver. CONCLUSIONS: These findings suggest 
      that CR-induced microbiota shapes the hepatic epigenome followed by altered 
      expression of genes responsible for bile acid metabolism.
CI  - (c) 2023. The Author(s).
FAU - Fan, Yun
AU  - Fan Y
AD  - State Key Laboratory of Reproductive Medicine, Center for Global Health, School 
      of Public Health, Nanjing Medical University, Nanjing, 211166, China.
AD  - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public 
      Health, Nanjing Medical University, Nanjing, 211166, China.
AD  - Department of Microbes and Infection, School of Public Health, Nanjing Medical 
      University, Nanjing, 211166, China.
FAU - Qian, Hong
AU  - Qian H
AD  - State Key Laboratory of Reproductive Medicine, Center for Global Health, School 
      of Public Health, Nanjing Medical University, Nanjing, 211166, China.
AD  - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public 
      Health, Nanjing Medical University, Nanjing, 211166, China.
FAU - Zhang, Meijia
AU  - Zhang M
AD  - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public 
      Health, Nanjing Medical University, Nanjing, 211166, China.
AD  - Department of Microbes and Infection, School of Public Health, Nanjing Medical 
      University, Nanjing, 211166, China.
FAU - Tao, Chengzhe
AU  - Tao C
AD  - State Key Laboratory of Reproductive Medicine, Center for Global Health, School 
      of Public Health, Nanjing Medical University, Nanjing, 211166, China.
AD  - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public 
      Health, Nanjing Medical University, Nanjing, 211166, China.
FAU - Li, Zhi
AU  - Li Z
AD  - State Key Laboratory of Reproductive Medicine, Center for Global Health, School 
      of Public Health, Nanjing Medical University, Nanjing, 211166, China.
AD  - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public 
      Health, Nanjing Medical University, Nanjing, 211166, China.
FAU - Yan, Wenkai
AU  - Yan W
AD  - State Key Laboratory of Reproductive Medicine, Center for Global Health, School 
      of Public Health, Nanjing Medical University, Nanjing, 211166, China.
AD  - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public 
      Health, Nanjing Medical University, Nanjing, 211166, China.
FAU - Huang, Yuna
AU  - Huang Y
AD  - State Key Laboratory of Reproductive Medicine, Center for Global Health, School 
      of Public Health, Nanjing Medical University, Nanjing, 211166, China.
AD  - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public 
      Health, Nanjing Medical University, Nanjing, 211166, China.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - State Key Laboratory of Reproductive Medicine, Center for Global Health, School 
      of Public Health, Nanjing Medical University, Nanjing, 211166, China.
AD  - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public 
      Health, Nanjing Medical University, Nanjing, 211166, China.
FAU - Xu, Qiaoqiao
AU  - Xu Q
AD  - State Key Laboratory of Reproductive Medicine, Center for Global Health, School 
      of Public Health, Nanjing Medical University, Nanjing, 211166, China.
AD  - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public 
      Health, Nanjing Medical University, Nanjing, 211166, China.
FAU - Wang, Xinru
AU  - Wang X
AD  - State Key Laboratory of Reproductive Medicine, Center for Global Health, School 
      of Public Health, Nanjing Medical University, Nanjing, 211166, China.
AD  - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public 
      Health, Nanjing Medical University, Nanjing, 211166, China.
FAU - Wade, Paul A
AU  - Wade PA
AD  - Eukaryotic Transcriptional Regulation Group, Epigenetics and Stem Cell Biology 
      Laboratory, National Institute of Environmental Health Sciences, Research 
      Triangle Park, NC, 27709, USA.
FAU - Xia, Yankai
AU  - Xia Y
AD  - State Key Laboratory of Reproductive Medicine, Center for Global Health, School 
      of Public Health, Nanjing Medical University, Nanjing, 211166, China.
AD  - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public 
      Health, Nanjing Medical University, Nanjing, 211166, China.
FAU - Qin, Yufeng
AU  - Qin Y
AD  - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public 
      Health, Nanjing Medical University, Nanjing, 211166, China. qiny@njmu.edu.cn.
AD  - Department of Microbes and Infection, School of Public Health, Nanjing Medical 
      University, Nanjing, 211166, China. qiny@njmu.edu.cn.
FAU - Lu, Chuncheng
AU  - Lu C
AUID- ORCID: 0000-0003-3689-9188
AD  - State Key Laboratory of Reproductive Medicine, Center for Global Health, School 
      of Public Health, Nanjing Medical University, Nanjing, 211166, China. 
      chunchenglu@njmu.edu.cn.
AD  - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public 
      Health, Nanjing Medical University, Nanjing, 211166, China. 
      chunchenglu@njmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230430
PL  - England
TA  - Genome Biol
JT  - Genome biology
JID - 100960660
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Chromatin)
RN  - 0 (Hnf4a protein, mouse)
RN  - 0 (Hepatocyte Nuclear Factor 4)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Models, Animal
MH  - *Caloric Restriction
MH  - *Gastrointestinal Microbiome
MH  - *Liver/physiology
MH  - Bile Acids and Salts/metabolism
MH  - Metabolism
MH  - Transcriptome
MH  - Chromatin/metabolism
MH  - Enhancer Elements, Genetic
MH  - Hepatocyte Nuclear Factor 4/metabolism
MH  - Epigenome
MH  - Male
MH  - Mice, Inbred C57BL
PMC - PMC10150505
OTO - NOTNLM
OT  - Bile acid metabolism
OT  - Caloric restriction
OT  - Gut microbiota
OT  - Hepatic epigenome
OT  - Metabolic adaptation
COIS- The authors declare that they have no competing interests.
EDAT- 2023/05/01 00:42
MHDA- 2023/05/02 06:41
PMCR- 2023/04/30
CRDT- 2023/04/30 23:15
PHST- 2022/06/12 00:00 [received]
PHST- 2023/04/11 00:00 [accepted]
PHST- 2023/05/02 06:41 [medline]
PHST- 2023/05/01 00:42 [pubmed]
PHST- 2023/04/30 23:15 [entrez]
PHST- 2023/04/30 00:00 [pmc-release]
AID - 10.1186/s13059-023-02938-5 [pii]
AID - 2938 [pii]
AID - 10.1186/s13059-023-02938-5 [doi]
PST - epublish
SO  - Genome Biol. 2023 Apr 30;24(1):98. doi: 10.1186/s13059-023-02938-5.