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

Sarah Talley, Raiza Bonomo, Chaitanya Gavini, Jomana Hatahet, Emily Gornick, Tyler Cook, Byeong Jae Chun, Pete Kekenes-Huskey, Gregory Aubert, Edward Campbell, Virginie Mansuy-Aubert

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numberdmm049313
JournalDMM Disease Models and Mechanisms
Volume15
Issue number6
DOIs
StatePublished - 2022
Externally publishedYes

Keywords

  • Caspase
  • Gut microbiome
  • Inflammasome
  • Mouse biosensor
  • Obesity
  • Western diet

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • General Biochemistry, Genetics and Molecular Biology

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