Adipose tissue IL-18 production is independent of caspase-1 and caspase-11.
Immun Inflamm Dis
; 12(4): e1241, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38629728
ABSTRACT
BACKGROUND:
Inflammation in adipose tissue, resulting from imbalanced caloric intake and energy expenditure, contributes to the metabolic dysregulation observed in obesity. The production of inflammatory cytokines, such as IL-1ß and IL-18, plays a key role in this process. While IL-1ß promotes insulin resistance and diabetes, IL-18 regulates energy expenditure and food intake. Previous studies have suggested that caspase-1, activated by the Nlrp3 inflammasome in response to lipid excess, mediates IL-1ß production, whereas activated by the Nlrp1b inflammasome in response to energy excess, mediates IL-18 production. However, this has not been formally tested.METHODS:
Wild-type and caspase-1-deficient Balb/c mice, carrying the Nlrp1b1 allele, were fed with regular chow or a high-fat diet for twelve weeks. Food intake and mass gain were recorded weekly. At the end of the twelve weeks, glucose tolerance and insulin resistance were evaluated. Mature IL-18 protein levels and the inflammatory process in the adipose tissue were determined. Fasting lipid and cytokine levels were quantified in the sera of the different experimental groups.RESULTS:
We found that IL-18 production in adipose tissue is independent of caspase-1 activity, regardless of the metabolic state, while Nlrp3-mediated IL-1ß production remains caspase-1 dependent. Additionally, caspase-1 null Balb/c mice did not develop metabolic abnormalities in response to energy excess from the high-fat diet.CONCLUSION:
Our findings suggest that IL-18 production in the adipose tissue is independent of Nlrp3 inflammasome and caspase-1 activation, regardless of caloric food intake. In contrast, Nlrp3-mediated IL-1ß production is caspase-1 dependent. These results provide new insights into the mechanisms underlying cytokine production in the adipose tissue during both homeostatic conditions and metabolic stress, highlighting the distinct roles of caspase-1 and the Nlrp inflammasomes in regulating inflammatory responses.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tecido Adiposo
/
Caspase 1
/
Interleucina-18
/
Caspases Iniciadoras
/
Proteína 3 que Contém Domínio de Pirina da Família NLR
Limite:
Animals
Idioma:
En
Revista:
Immun Inflamm Dis
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
México
País de publicação:
Reino Unido