Time-of-day-dependent variation of the human liver transcriptome and metabolome is disrupted in MASLD

Johanns, Manuel; Haas, Joel T.; Raverdy, Violetta; Vandel, Jimmy; Chevalier-Dubois, Julie; Guille, Loic; Derudas, Bruno; Legendre, Benjamin; Caiazzo, Robert; Verkindt, Helene; Gnemmi, Viviane; Leteurtre, Emmanuelle; Derhourhi, Mehdi; Bonnefond, Amélie; Froguel, Philippe; Eeckhoute, Jérôme; Lassailly, Guillaume; Mathurin, Philippe; Pattou, François; Staels, Bart; Lefebvre, Philippe

doi:10.1016/j.jhepr.2023.100948

JHEP Reports

2024

DOI: 10.1016/j.jhepr.2023.100948

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Time-of-day-dependent variation of the human liver transcriptome and metabolome is disrupted in MASLD

Manuel Johanns,

Joel T. Haas,

Violetta Raverdy

et al.

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Cited by 2 publications

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Getting in the zone: Metabolite transport across liver zones

van de Graaf,

Paulusma,

In het Panhuis

2024

Acta Physiologica

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The liver has many functions including the regulation of nutrient and metabolite levels in the systemic circulation through efficient transport into and out of hepatocytes. To sustain these functions, hepatocytes display large functional heterogeneity. This heterogeneity is reflected by zonation of metabolic processes that take place in different zones of the liver lobule, where nutrient‐rich blood enters the liver in the periportal zone and flows through the mid‐zone prior to drainage by a central vein in the pericentral zone. Metabolite transport plays a pivotal role in the division of labor across liver zones, being either transport into the hepatocyte or transport between hepatocytes through the blood. Signaling pathways that regulate zonation, such as Wnt/β‐catenin, have been shown to play a causal role in the development of metabolic dysfunction‐associated steatohepatitis (MASH) progression, but the (patho)physiological regulation of metabolite transport remains enigmatic. Despite the practical challenges to separately study individual liver zones, technological advancements in the recent years have greatly improved insight in spatially divided metabolite transport. This review summarizes the theories behind the regulation of zonation, diurnal rhythms and their effect on metabolic zonation, contemporary techniques used to study zonation and current technological challenges, and discusses the current view on spatial and temporal metabolite transport.

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Getting in the zone: Metabolite transport across liver zones

van de Graaf,

Paulusma,

In het Panhuis

2024

Acta Physiologica

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Nuclear receptors: pathophysiological mechanisms and drug targets in liver disease

Dubois,

Lefebvre,

Staels

et al. 2024

Gut

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Nuclear receptors (NRs) are ligand-dependent transcription factors required for liver development and function. As a consequence, NRs have emerged as attractive drug targets in a wide range of liver diseases. However, liver dysfunction and failure are linked to loss of hepatocyte identity characterised by deficient NR expression and activities. This might at least partly explain why several pharmacological NR modulators have proven insufficiently efficient to improve liver functionality in advanced stages of diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). In this perspective, we review the most recent advances in the hepatic NR field and discuss the contribution of multiomic approaches to our understanding of their role in the molecular organisation of an intricated transcriptional regulatory network, as well as in liver intercellular dialogues and interorgan cross-talks. We discuss the potential benefit of novel therapeutic approaches simultaneously targeting multiple NRs, which would not only reactivate the hepatic NR network and restore hepatocyte identity but also impact intercellular and interorgan interplays whose importance to control liver functions is further defined. Finally, we highlight the need of considering individual parameters such as sex and disease stage in the development of NR-based clinical strategies.

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Time-of-day-dependent variation of the human liver transcriptome and metabolome is disrupted in MASLD

Cited by 2 publications

References 45 publications

Getting in the zone: Metabolite transport across liver zones

Getting in the zone: Metabolite transport across liver zones

Nuclear receptors: pathophysiological mechanisms and drug targets in liver disease

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