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

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)
JournalDisease models & mechanisms
Volume15
Issue number6
DOIs
StatePublished - Jun 1 2022

Keywords

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

ASJC Scopus subject areas

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

Fingerprint

Dive into the research topics of 'Monitoring of inflammation using novel biosensor mouse model reveals tissue- and sex-specific responses to Western diet'. Together they form a unique fingerprint.

Cite this