PPARβ/δ: linking metabolism to regeneration
Open accessAbstract
In contrast to the general belief that regeneration is a rare event, mainly occurring in simple organisms, the ability of regeneration is widely distributed in the animal kingdom. Yet, the efficiency and extent of regeneration varies greatly. Humans can recover from blood loss as well as damage to tissues like bone and liver. Yet damage to the heart and brain cannot be reversed, resulting in scaring. Thus, there is a great interest in understanding the molecular mechanisms of naturally occurring regeneration and to apply this knowledge to repair human organs. During regeneration, injury-activated immune cells induce wound healing, extracellular matrix remodeling, migration, dedifferentiation and/or proliferation with subsequent differentiation of somatic or stem cells. An anti-inflammatory response stops the regenerative process, which ends with tissue remodeling to achieve the original functional state. Notably, many of these processes are associated with enhanced glycolysis. Therefore, peroxisome proliferator-activated receptor (PPAR) β/δ—which is known to be involved for example in lipid catabolism, glucose homeostasis, inflammation, survival, proliferation, differentiation, as well as mammalian regeneration of the skin, bone and liver—appears to be a promising target to promote mammalian regeneration. This review summarizes our current knowledge of PPARβ/δ in processes associated with wound healing and regeneration.
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Anti-inflammatory effects and regulatory roles in glucose metabolism have been reported for both PPARα and PPARδ.
“Furthermore, anti-inflammatory effects and regulatory roles in glucose metabolism have been reported for both isoforms (Lefebvre et al., 2006;Neels and Grimaldi, 2014;Magadum and Engel, 2018).”
From The Peroxisome Proliferator–Activated Receptor (PPAR)-γ Antagonist 2-Chloro-5-Nitro-N-Phenylbenzamide (GW9662) Triggers Perilipin 2 Expression via PPARδ and Induces Lipogenesis and Triglyceride Accumulation in Human THP-1 Macrophages (2020) · cites this paper as Magadum and Engel, 2018
Section 3.3 (page not provided) describes anti-inflammatory properties of PPARβ/δ, and Section 3.1 reports that its overexpression increases glucose utilization in the liver and heart. The paper identifies PPARα as another isoform but does not establish both effects for PPARα, so it supports only the PPARδ portion of the claim. (LLM, conf=0.88)
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- Authors
- Magadum, A., & Engel, F. B.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Corresponding author
- Engel, Felix B.
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2018-07-10
- Volume
- 19
- Issue
- 7
- Pages
- 2013
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC6073704
- OpenAlex
- W2835900673
- Cited by
- 110
- References
- 178
- Citations by year
- 2026: 6 · 2025: 20 · 2024: 16 · 2023: 11 · 2022: 10 · 2021: 22 · 2020: 16 · 2019: 6 · 2018: 1 · 2017: 1
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- OPUS Repository (Kooperativer Bibliotheksverbund Berlin-Brandenburg) (submittedVersion, cc-by)
- Funders
- Friedrich-Alexander-Universität Erlangen-Nürnberg (Cycle in Disease and Regeneration (CYDER))
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- PPARδ, peroxisome proliferator-activated receptors, tissue regeneration, wound healing, glycolysis, inflammation, extracellular matrix remodeling, tissue remodeling, anti-inflammatory response, regenerative medicine
- MeSH terms
- Animals, Cell Differentiation, Glycolysis, Humans, Regeneration, Wound Healing, PPAR delta, PPAR-beta, Lipid Metabolism, Wnt Signaling Pathway
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