Impact of thermogenesis induced by chronic β3-adrenergic receptor agonist treatment on inflammatory and infectious response during bacteremia in mice

PLoS One. 2021 Aug 26;16(8):e0256768. doi: 10.1371/journal.pone.0256768. eCollection 2021.

Abstract

White adipocytes store energy differently than brown and brite adipocytes which dissipate energy under the form of heat. Studies have shown that adipocytes are able to respond to bacteria thanks to the presence of Toll-like receptors at their surface. Despite this, little is known about the involvement of each class of adipocytes in the infectious response. We treated mice for one week with a β3-adrenergic receptor agonist to induce activation of brown adipose tissue and brite adipocytes within white adipose tissue. Mice were then injected intraperitoneally with E. coli to generate acute infection. The metabolic, infectious and inflammatory parameters of the mice were analysed during 48 hours after infection. Our results shown that in response to bacteria, thermogenic activity promoted a discrete and local anti-inflammatory environment in white adipose tissue characterized by the increase of the IL-1RA secretion. More generally, activation of brown and brite adipocytes did not modify the host response to infection including no additive effect with fever and an equivalent bacteria clearance and inflammatory response. In conclusion, these results suggest an IL-1RA-mediated immunomodulatory activity of thermogenic adipocytes in response to acute bacterial infection and open a way to characterize their effect along more chronic infection as septicaemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Beige / drug effects
  • Adipocytes, Beige / metabolism
  • Adipocytes, White / drug effects
  • Adipocytes, White / metabolism
  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Adrenergic Agonists / pharmacology
  • Animals
  • Bacteremia / drug therapy*
  • Bacteremia / genetics
  • Bacteremia / metabolism
  • Bacteremia / microbiology
  • Dioxoles / pharmacology
  • Disease Models, Animal
  • Energy Metabolism / drug effects
  • Escherichia coli / pathogenicity
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / microbiology
  • Interleukin 1 Receptor Antagonist Protein / genetics*
  • Mice
  • Receptors, Adrenergic, beta-3 / genetics*
  • Thermogenesis / drug effects*
  • Toll-Like Receptors / genetics

Substances

  • Adrb3 protein, mouse
  • Adrenergic Agonists
  • Dioxoles
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Receptors, Adrenergic, beta-3
  • Toll-Like Receptors
  • disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate

Grants and funding

DFP received a fellowshig from "Société Francophone du Diabète (SFD)/Pierre Fabre Médicament" 2017. https://www.sfdiabete.org/ The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.