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

Patrick Munro,Didier F Pisani,Samah Rekima,Agnès Loubat,Christophe Duranton,Laurent Boyer

doi:10.1371/journal.pone.0256768

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.

Highlights

White adipocytes, main constituents of white adipose tissue (WAT) are specialized in the storage and release of energy, while brown adipocytes dissipate this energy in the form of heat [1]
It has been demonstrated that mice infected with Yersinia pseudotuberculosis accumulated memory T lymphocytes in adipose tissue, which are able to protect mice from a secondary infection [26]
We focused on the impact of brite and brown adipocytes, both displaying a thermogenic function, on the local and systemic inflammation in response to bacterial infection

Summary

Introduction

Main constituents of white adipose tissue (WAT) are specialized in the storage and release of energy (carbohydrates, lipids), while brown adipocytes dissipate this energy in the form of heat (thermogenesis) [1]. Brown adipocytes constitute the brown adipose tissue (BAT) but can be found within the WAT. They are called beige or brite adipocytes (for "brown in white”) and have an increased thermogenesis capacity in response to prolonged exposure to cold, for instance [2].

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Conclusion