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Monitoring of inflammation using novel biosensor mouse model reveals tissue- and sex-specific responses to Western diet

Obesity is an epidemic, and it is characterized by a state of low-grade systemic inflammation. A key component of inflammation is the activation of inflammasomes, multiprotein complexes that form in response to danger signals and that lead to activation of caspase-1. Previous studies have found that...

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Detalles Bibliográficos
Autores principales: Talley, Sarah, Bonomo, Raiza, Gavini, Chaitanya, Hatahet, Jomana, Gornick, Emily, Cook, Tyler, Chun, Byeong Jae, Kekenes-Huskey, Pete, Aubert, Gregory, Campbell, Edward, Mansuy-Aubert, Virginie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235879/
https://www.ncbi.nlm.nih.gov/pubmed/35466363
http://dx.doi.org/10.1242/dmm.049313
Descripción
Sumario:Obesity is an epidemic, and it is characterized by a state of low-grade systemic inflammation. A key component of inflammation is the activation of inflammasomes, multiprotein complexes that form in response to danger signals and that lead to activation of caspase-1. Previous studies have found that a Westernized diet induces activation of inflammasomes and production of inflammatory cytokines. Gut microbiota metabolites, including the short-chain fatty acid butyrate, have received increased attention as underlying some obesogenic features, but the mechanisms of action by which butyrate influences inflammation in obesity remain unclear. We engineered a caspase-1 reporter mouse model to measure spatiotemporal dynamics of inflammation in obese mice. Concurrent with increased capsase-1 activation in vivo, we detected stronger biosensor signal in white adipose and heart tissues of obese mice ex vivo and observed that a short-term butyrate treatment affected some, but not all, of the inflammatory responses induced by Western diet. Through characterization of inflammatory responses and computational analyses, we identified tissue- and sex-specific caspase-1 activation patterns and inflammatory phenotypes in obese mice, offering new mechanistic insights underlying the dynamics of inflammation.