(745.13) Unravelling the Effects of Chronic Corticosterone Exposure in Brown Adipose Tissue Whitening
Monday, April 4, 2022
10:15 AM – 12:15 PM
Location: Exhibit/Poster Hall A-B - Pennsylvania Convention Center
Poster Board Number: E368
Jocelyn Bel (Lakehead University), Sarah Niccoli (Northern Ontario School of Medicine), Neelam Khaper (Northern Ontario School of Medicine, Northern Ontario School of Medicine), T.C. Tai (Northern Ontario School of Medicine, Northern Ontario School of Medicine, Northern Ontario School of Medicine, Northern Ontario School of Medicine), Simon Lees (Northern Ontario School of Medicine, Northern Ontario School of Medicine)
Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis and has been found to play a role in improving whole-body metabolism. While the beiging of white adipose tissue is a growing area of interest, the possibility of the BAT depot to “whiten” and store more triglycerides also has metabolic and subsequent health implications. Currently, there are limited studies that examine the effects of chronic stress and its ability to induce a white-like phenotype in the BAT depot. Even fewer studies have directly compared the activation and whitening of this depot. This study examined a chronic four-week exposure to murine stress hormone corticosterone compared to the β3-adrenergic receptor agonist mirabegron. This allows for a direct comparison between the effect of corticosterone on whitening and the mirabegron-induced activation in BAT of C57BL/6 male mice. Corticosterone-treated mice had significantly higher body weight (p≤0.05) and BAT mass (p≤0.05), increased lipid droplet area (p≤0.05), were insulin resistant (p≤0.05) and had significantly elevated expression of uncoupling protein 1 (UCP-1) in BAT (p≤0.05) while the mitochondrial content marker citrate synthase remained unchanged. This whitened phenotype has not been previously associated with increased uncoupling proteins under chronic stress and may represent a compensatory response being initiated under these conditions. Mirabegron-treated mice had body and BAT weights comparable to controls, remained insulin sensitive, and had mitochondrial content and lipid droplet area similar to controls. Mirabegron-treated mice also had significantly elevated expressions of UCP-1 (p≤0.05) compared to controls, however, the elevated expression was notably less than that of the corticosterone treatment group. The possible compensatory mechanism with increased UCP-1 in a whitened phenotype appears to elicit a stronger degree of uncoupling than the activation of BAT via the β3-adrenergic receptor itself. The implications of BAT whitening and activation are usually thought of as opposing processes; however, this study clearly illustrates that they may intersect in ways not previously discovered. These findings further illustrate the complexity of BAT and how much is still left to be examined with this tissue.
Support or Funding Information
This work was supported by the Natural Sciences and Engineering Research Council of Canada CRD (Grant number CRDPJ/494077-16) and the Nuclear Innovation Institute.