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Cited by 6Chronic Kidney Disease and DiabetesPeroxisome Proliferator-Activated ReceptorsAutophagy in Disease and Therapy

ACOT12, a novel factor in the pathogenesis of kidney fibrosis, modulates ACBD5.

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Kim, Ee Hyun, Kim, Mi Kyung, Choe, MiSun, Ryu, Ji Hyun, Pak, Eun Seon, Ha, Hunjoo, Jin, Eun-Jung·2025·Experimental & Molecular Medicine
DOI 10.1038/s12276-025-01406-3PMC PMC11873122
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Abstract

Lipid metabolism, particularly fatty acid oxidation dysfunction, is a major driver of renal fibrosis. However, the detailed regulatory mechanisms underlying this process remain unclear. Here we demonstrated that acyl-CoA thioesterase 12 (Acot12), an enzyme involved in the hydrolysis of acyl-CoA thioesters into free fatty acids and CoA, is a key regulator of lipid metabolism in fibrotic kidneys. A significantly decreased level of ACOT12 was observed in kidney samples from human patients with chronic kidney disease as well as in samples from mice with kidney injuries. Acot12 deficiency induces lipid accumulation and fibrosis in mice subjected to unilateral ureteral obstruction (UUO). Fenofibrate administration does not reduce renal fibrosis in Acot12 −/− mice with UUO. Moreover, the restoration of peroxisome proliferator-activated receptor α (PPARα) in Acot12 −/− Pparα −/− kidneys with UUO exacerbated lipid accumulation and renal fibrosis, whereas the restoration of Acot12 in Acot12 −/− Pparα −/− kidneys with UUO significantly reduced lipid accumulation and renal fibrosis, suggesting that, mechanistically, Acot12 deficiency exacerbates renal fibrosis independently of PPAR α . In Acot12 −/− kidneys with UUO, a reduction in the selective autophagic degradation of peroxisomes and pexophagy with a decreased level of ACBD5 was observed. In conclusion, our study demonstrates the functional role and mechanistic details of Acot12 in the progression of renal fibrosis, provides a preclinical rationale for regulating Acot12 expression and presents a novel means of preventing renal fibrosis.

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  • A recent study reported a correlation between kidney fibrosis and a reduction in pexophagy, which was associated with downregulation of ACBD5.

    “It should, however, be mentioned that a recent study reported a correlation between kidney fibrosis and a reduction in pexophagy, which was associated with downregulation of ACBD5 (Kim et al., 2025).”

    From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Kim et al., 2025

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Cited by

Sorted by citations

Authors
Kim, E. H., Kim, M. K., Choe, M., Ryu, J. H., Pak, E. S., Ha, H., & Jin, E.-J.
Affiliations
  • Ewha Womans University (KR)
  • Keimyung University (KR)
  • Wonkwang University (KR)
Corresponding author
  • Ha, Hunjoo
  • Jin, Eun-Jung
ORCID
Venue
Experimental & Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2025-02-13
Volume
57
Issue
2
Pages
478-488
ISSN
  • 1226-3613 (ISSN-L)
  • 2092-6413
DOI
10.1038/s12276-025-01406-3
PMC
PMC11873122
OpenAlex
W4407556694
Cited by
6
References
2
Citations by year
2026: 4 · 2025: 2
FWCI
4.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Experimental & Molecular Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National Research Foundation of Korea (2022R1A4A1031259 and 2021R1I1A3041149, 2022R1A6A3A13069395)
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
renal fibrosis, chronic kidney disease, lipid metabolism, fatty acid oxidation, pexophagy, peroxisome degradation, PPARα, lipid accumulation, unilateral ureteral obstruction, fenofibrate
MeSH terms
Animals, Autophagy, Disease Models, Animal, Fibrosis, Humans, Kidney, Kidney Diseases, Male, Mice, Inbred C57BL, Palmitoyl-CoA Hydrolase, Thiolester Hydrolases, Ureteral Obstruction, Mice, Knockout, Peroxisomes, PPAR alpha, Lipid Metabolism, Mice, Renal Insufficiency, Chronic

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