Cellular carbon stress is a mediator of obesity-associated osteoarthritis development.
Osteoarthritis Cartilage
; 29(9): 1346-1350, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-33984464
ABSTRACT
OBJECTIVE:
'Carbon stress' is a newly found mechanism that links obesity and dysregulated metabolism. It is defined as the cellular accumulation of metabolites during obesity post-translationally modifying metabolic proteins and decreasing their enzymatic activity. The objective of this study was to investigate if 'carbon stress' also occurs in cartilage and contributes to obesity associated OA development.METHODS:
We histologically evaluated for OA pathology in wild-type (WT) and hyperphagic mice (Pomc-neuron specific enhancer one deficient, PomcΔ1) that were subjected to standard chow (Chow, n = 6 for both genotypes) or high-fat feeding (HFD, n = 7 for both genotypes). Joints were stained and quantified for 'carbon stress' markers, including succinyl-lysine (SCK), malonyl-lysine (MAK), and acetyl-lysine (ACK). Lastly, we used a mouse model with deletion of Sirt5 (n = 7), which is an enzyme that removes SCK and MAK, to test if changing the abundance of 'carbon stress' would affect OA pathogenesis.RESULTS:
Both HFD and Pomc deficiency associated obesity induced cartilage degeneration as well as greater abundance of SCK and MAK in the cartilage. PomcΔ1-HFD mice did not have exacerbated OA pathology as compared to PomcΔ1-Chow mice. ACK was mildly increased in the obese groups comparing to WT-Chow. Sirt5-/- mice developed early-OA like phenotype at 40 weeks of age as characterized by cartilage fibrillation and more hypertrophic chondrocytes. Cartilage from Sirt5-/- mice also had increased SCK and MAK, while ACK remained unchanged comparing to WT mice.CONCLUSION:
Our data suggests that carbon stress also occurs in cartilage tissue during obesity and can potentially contribute to obesity-associated OA.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
/
Cartilagem
/
Doenças das Cartilagens
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Doenças Metabólicas
/
Obesidade
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article