Activation of beta-adrenergic receptor signaling prevents glucocorticoid-induced obesity and adipose tissue dysfunction in male mice
| Autor: | Manuel Gado, Annett Heinrich, Denise Wiedersich, Katrin Sameith, Andreas Dahl, Vasileia I. Alexaki, Michael M. Swarbrick, Ulrike Baschant, Ingo Grafe, Nikolaos Perakakis, Stefan R. Bornstein, Martina Rauner, Lorenz C. Hofbauer, Holger Henneicke |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.00259.2022 |
| Popis: | Elevated serum concentrations of glucocorticoids (GCs) result in excessive lipid accumulation in white adipose tissue (WAT) as well as dysfunction of thermogenic brown adipose tissue (BAT) - ultimately leading to the development of obesity and metabolic disease. Here, we hypothesized that activation of the sympathetic nervous system either via cold exposure or use of a selective β3-adrenergic receptor (β3-AR) agonist alleviates the adverse metabolic effects of chronic GC exposure in rodents. To this end, male 10-week-old C57BL/6NRj mice were treated with corticosterone via drinking water or placebo for 4 weeks while being maintained at 29°C (thermoneutrality), 22°C (room temperature) or 13°C (cold temperature); in a follow-up study mice received a selective β3-AR agonist or placebo with and without corticosterone while maintained at room temperature. Body weight and food intake were monitored throughout the study. Histological and molecular analyses were performed on white and brown adipose depots. Cold exposure not only preserved the thermogenic function of brown adipose tissue, but also reversed GC-induced lipid accumulation in white adipose tissue and corrected GC-driven obesity, hyperinsulinemia and hyperglycemia. The metabolic benefits of cold exposure were associated with enhanced sympathetic activity in adipose tissue, thus potentially linking an increase in sympathetic signaling to the observed metabolic benefits. In line with this concept, chronic administration of a selective β3-AR agonist reproduced the beneficial metabolic effects of cold adaption during exposure to exogenous GCs. This preclinical study demonstrates the potential of β3-AR as a therapeutic target in the management and prevention of GC-induced metabolic disease. |
| Databáze: | OpenAIRE |
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