The Effects of Chronic Stress on Brown Adipose Tissue Remodeling and Metabolism

Abstract

Adipose tissue has been found to exist in two predominant forms, white and brown. White adipose tissue (WAT) is the body's conventional storage organ, while brown adipose tissue (BAT) is responsible for non-shivering thermogenesis, which allows mammals to produce heat and regulate body temperature. Studies examining BAT and its role in whole-body metabolism have found that active BAT can lead to improved metabolic outcomes. While the beiging/ browning of WAT is a growing area of interest, the possibility of the BAT depot to “whiten” and store more triglycerides and adopt a lipid storage phenotype of WAT may have important health implications. Currently, there are limited studies that examine the direct effects of chronic stress in BAT and its ability to induce a white-like phenotype in this adipose tissue depot. This current research aimed to determine the impact of high levels of the murine stress hormone, corticosterone, on the whitening process of BAT. Six-week-old male C57BL/6J mice were exposed to high levels (100µg/ml) of corticosterone in their drinking water for four weeks. The effect of the corticosterone on BAT was investigated for its impact on insulin resistance, and the expression of uncoupling protein 1 (UCP1), which is integral to the non-shivering thermogenesis pathway. Corticosterone treatment significantly (p≤0.05) increased body weight, both WAT and BAT mass, and adipocyte size in each adipose depot. Corticosterone treatment significantly (p≤0.05) increased plasma insulin concentrations. The homeostatic model of assessment for insulin resistance (HOMA-IR) demonstrated that the corticosterone treated mice were also significantly (p≤0.05) more insulin resistant than controls. Surprisingly, the BAT of the corticosterone treated mice had significantly (p≤0.05) higher protein expression levels of UCP1 than controls. The alterations found in our in vivo model illustrated that chronic treatment with corticosterone for 4 weeks resulted in tissue remodeling, altered glucose metabolism, and adipose tissue whitening. By understanding these altered adipocyte morphologies and metabolic phenotypes in mice under chronic stress, we will be better equipped to uncover pathological effects of metabolic diseases weighing the world down today.