Cited by 87Telomeres, Telomerase, and SenescenceAdipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and Metabolism

Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities

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Chen, Yih-Wen, Harris, Robert A., Hatahet, Zafer, Chou, Kai-ming·2015·Proceedings of the National Academy of Sciences

Abstract

Significance: The metabolic syndrome has evolved to be a major health issue globally. The association between genome integrity and metabolic abnormalities is not well understood. Our results indicate that increased DNA damage and persistent activation of the DNA damage response induce adipocyte senescence in DNA polymerase η knockout ( pol η −/− ) mice. Suppression of adipocyte senescence with a p53 inhibitor, pifithrin-α, alleviated metabolic abnormalities in pol η −/− mice. An increase or decrease in DNA damage affected the senescence status of adipocytes accordingly, which was also in concordance with the severity of metabolic abnormalities in the pol η −/− mice. Our current results indicate that reduced genome integrity plays a causative role in provoking adipocyte senescence that leads to development of obesity and insulin resistance.

Integrity signals

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Crossref · 10.1073/pnas.1506954112

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57 of 57 references verified0 citation errors · 0 not checkable

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Authors
Chen, Y.-W., Harris, R. A., Hatahet, Z., & Chou, K.-M.
Affiliations
  • Indiana University Indianapolis (US)
  • Richard L. Roudebush VA Medical Center (US)
  • Northwestern State University (US)
Venue
Proceedings of the National Academy of Sciences
Published
2015-08-03
Volume
112
Issue
33
Pages
E4556-64
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2146336603
Cited by
86
References
57
Citations by year
2026: 1 · 2025: 5 · 2024: 7 · 2023: 12 · 2022: 24 · 2021: 16 · 2020: 7 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 3
FWCI
2.46
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
  • PMC
Funders
  • HHS | NIH | National Cancer Institute (112446)
  • U.S. Department of Veterans Affairs (BLRD Merit Award)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
adipocyte senescence, adipose tissue, obesity, insulin resistance, DNA damage response, p53, pifithrin-alpha, metabolic syndrome, hepatic steatosis, hyperleptinemia, hyperinsulinemia, impaired glucose tolerance, high-fat diet, sodium arsenite, N-acetylcysteine, metformin, interleukin-6, TNF-α, senescence-associated β-galactosidase
MeSH terms
Y-Family DNA Polymerases, Adipose Tissue, Animals, Blood Glucose, DNA Damage, DNA-Directed DNA Polymerase, Genotype, Immunohistochemistry, Insulin Resistance, Macrophages, Male, Neoplasm Transplantation, Toluene, Gene Expression Regulation, Neoplastic, Cellular Senescence, Reactive Oxygen Species, Adipocytes, Mice, Knockout, Comet Assay, Metabolic Syndrome, 3T3-L1 Cells, Mice, Benzothiazoles

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