Imperial College London
Professor Philippe Froguel

ProfessorPhilippeFroguel

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Chair in Genomic Medicine
 
 
 
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Contact

 

+44 (0)20 7594 6520p.froguel

 
 
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Assistant

 

Mrs Patricia Murphy +44 (0)20 7594 1603

 
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Location

 

E306Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Johanns:2024:10.1016/j.jhepr.2023.100948,
author = {Johanns, M and Haas, JT and Raverdy, V and Vandel, J and Chevalier-Dubois, J and Guille, L and Derudas, B and Legendre, B and Caiazzo, R and Verkindt, H and Gnemmi, V and Leteurtre, E and Derhourhi, M and Bonnefond, A and Froguel, P and Eeckhoute, J and Lassailly, G and Mathurin, P and Pattou, F and Staels, B and Lefebvre, P},
doi = {10.1016/j.jhepr.2023.100948},
journal = {JHEP Rep},
title = {Time-of-day-dependent variation of the human liver transcriptome and metabolome is disrupted in MASLD.},
url = {http://dx.doi.org/10.1016/j.jhepr.2023.100948},
volume = {6},
year = {2024}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND & AIMS: Liver homeostasis is ensured in part by time-of-day-dependent processes, many of them being paced by the molecular circadian clock. Liver functions are compromised in metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), and clock disruption increases susceptibility to MASLD progression in rodent models. We therefore investigated whether the time-of-day-dependent transcriptome and metabolome are significantly altered in human steatotic and MASH livers. METHODS: Liver biopsies, collected within an 8 h-window from a carefully phenotyped cohort of 290 patients and histologically diagnosed to be either normal, steatotic or MASH hepatic tissues, were analyzed by RNA sequencing and unbiased metabolomic approaches. Time-of-day-dependent gene expression patterns and metabolomes were identified and compared between histologically normal, steatotic and MASH livers. RESULTS: Herein, we provide a first-of-its-kind report of a daytime-resolved human liver transcriptome-metabolome and associated alterations in MASLD. Transcriptomic analysis showed a robustness of core molecular clock components in steatotic and MASH livers. It also revealed stage-specific, time-of-day-dependent alterations of hundreds of transcripts involved in cell-to-cell communication, intracellular signaling and metabolism. Similarly, rhythmic amino acid and lipid metabolomes were affected in pathological livers. Both TNFα and PPARγ signaling were predicted as important contributors to altered rhythmicity. CONCLUSION: MASLD progression to MASH perturbs time-of-day-dependent processes in human livers, while the differential expression of core molecular clock components is maintained. IMPACT AND IMPLICATIONS: This work characterizes the rhythmic patterns of the transcriptome and metabolome in the human liver. Using a cohort of well-phenotyped patients (n = 290) for whom the time-of-day at biopsy
AU  - Johanns,M
AU  - Haas,JT
AU  - Raverdy,V
AU  - Vandel,J
AU  - Chevalier-Dubois,J
AU  - Guille,L
AU  - Derudas,B
AU  - Legendre,B
AU  - Caiazzo,R
AU  - Verkindt,H
AU  - Gnemmi,V
AU  - Leteurtre,E
AU  - Derhourhi,M
AU  - Bonnefond,A
AU  - Froguel,P
AU  - Eeckhoute,J
AU  - Lassailly,G
AU  - Mathurin,P
AU  - Pattou,F
AU  - Staels,B
AU  - Lefebvre,P
DO  - 10.1016/j.jhepr.2023.100948
PY  - 2024///
TI  - Time-of-day-dependent variation of the human liver transcriptome and metabolome is disrupted in MASLD.
T2  - JHEP Rep
UR  - http://dx.doi.org/10.1016/j.jhepr.2023.100948
UR  - https://www.ncbi.nlm.nih.gov/pubmed/38125300
VL  - 6
ER  -
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