Cited by 125Peroxisome Proliferator-Activated ReceptorsCholesterol and Lipid MetabolismParaoxonase enzyme and polymorphisms
PPARs in liver physiology
Open accessBerthier, Alexandre, Johanns, Manuel, Zummo, Francesco Paolo, Lefebvre, Philippe, Staels, Bart·2021·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Abstract
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and transcriptional modulators with crucial functions in hepatic and whole-body energy homeostasis. Besides their well-documented roles in lipid and glucose metabolism, emerging evidence also implicate PPARs in the control of other processes such as inflammatory responses. Recent technological advances, such as single-cell RNA sequencing, have allowed to unravel an unexpected complexity in the regulation of PPAR expression, activity and downstream signaling. Here we provide an overview of the latest advances in the study of PPARs in liver physiology, with a specific focus on formerly neglected aspects of PPAR regulation, such as tissular zonation, cellular heterogeneity, circadian rhythms, sexual dimorphism and species-specific features.
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General hepatocyte-specific eRegulons were found for CEBPA, HNF1A, HNF4A, ONECUT1, FOXA1 and NFIB, and zonation-associated eRegulons such as ESR1 and SOX9 periportally and PPARG and AR pericentrally.
“We found general hepatocyte-specific eRegulons for CEBPA, HNF1A, HNF4A, ONECUT1, FOXA1 and NFIB21–23, and zonation-associated eRegulons such as ESR1 and SOX9 periportally24,25 and PPARG and AR pericentrally26,27.”
From Single-cell spatial multi-omics and deep learning dissect enhancer-driven gene regulatory networks in liver zonation (2024) · cites this paper as [26]
Section 3.2, Liver zonation (page not supplied), reports striking centrilobular Pparg expression in mouse hepatocytes, supporting the pericentral PPARG association. It does not report a PPARG eRegulon or establish pericentral AR eRegulon activity. (LLM, conf=0.86)
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The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease
Díaz, L. A., Arab, J. P., Louvet, A., Bataller, R., & Arrese, M. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00822-y · Cited by 207 · see citing works
Bravo González-Blas, C., Matetovici, I., Hillen, H., Taskiran, I. I., Vandepoel, R., Christiaens, V., Sansores-García, L., Verboven, E., Hulselmans, G., Poovathingal, S., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-023-01316-4 · Cited by 85 · see citing works
“We found general hepatocyte-specific eRegulons for CEBPA, HNF1A, HNF4A, ONECUT1, FOXA1 and NFIB 21–23 , and zonation-associated eRegulons such as ESR1 and SOX9 peripor-tally 24,25 and PPARG and AR pericentrally 26,27 .”
- Authors
- Berthier, A., Johanns, M., Zummo, F. P., Lefebvre, P., & Staels, B.
- Affiliations
- Inserm (FR)
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 1867
- Issue
- 5
- Pages
- 166097
- ISSN
- 0925-4439 (ISSN-L)
- OpenAlex
- W3126234421
- Cited by
- 125
- References
- 19
- Citations by year
- 2026: 23 · 2025: 30 · 2024: 37 · 2023: 18 · 2022: 13 · 2021: 4
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 365 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Digital Access to Libraries (submittedVersion, other-oa)
- LillOA (Université de Lille (University Of Lille)) (submittedVersion)
- Funders
- European Genomic Institute for Diabetes (694717)
- European Commission (694717)
- Agence Nationale de la Recherche (ANR-10-LABX-0046)
- Fondation pour la Recherche Médicale (DEQ20150331724)
- Wallonie-Bruxelles International
- European Regional Development Fund
- H2020 European Research Council (694717)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- peroxisome proliferator-activated receptors, liver physiology, lipid metabolism, glucose metabolism, inflammation, single-cell RNA sequencing, cellular heterogeneity, circadian rhythm, sexual dimorphism, species differences, nuclear receptors
- MeSH terms
- Animals, Homeostasis, Humans, Liver, Liver Diseases, Signal Transduction, Peroxisome Proliferator-Activated Receptors
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