Adipolin protects against renal injury via PPARα-dependent reduction of inflammasome activation.
Cell biology
Immunology
Molecular biology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
19 May 2023
19 May 2023
Historique:
received:
12
09
2022
revised:
06
02
2023
accepted:
04
04
2023
medline:
30
5
2023
pubmed:
30
5
2023
entrez:
30
5
2023
Statut:
epublish
Résumé
Although chronic kidney disease (CKD) is a major health problem worldwide, its underlining mechanism is incompletely understood. We previously identified adipolin as an adipokine which provides benefits for cardiometabolic diseases. Here, we investigated the role of adipolin in the development of CKD. Adipolin-deficiency exacerbated urinary albumin excretion, tubulointerstitial fibrosis and oxidative stress of remnant kidneys in mice after subtotal nephrectomy through inflammasome activation. Adipolin positively regulated the production of ketone body, β-hydroxybutyrate (BHB) and expression of a catalytic enzyme producing BHB, HMGCS2 in the remnant kidney. Treatment of proximal tubular cells with adipolin attenuated inflammasome activation through the PPARα/HMGCS2-dependent pathway. Furthermore, systemic administration of adipolin to wild-type mice with subtotal nephrectomy ameliorated renal injury, and these protective effects of adipolin were diminished in PPARα-deficient mice. Thus, adipolin protects against renal injury by reducing renal inflammasome activation through its ability to induce HMGCS2-dependent ketone body production via PPARα activation.
Identifiants
pubmed: 37250342
doi: 10.1016/j.isci.2023.106591
pii: S2589-0042(23)00668-5
pmc: PMC10214396
doi:
Types de publication
Journal Article
Langues
eng
Pagination
106591Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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