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Endocrine Abstracts (2021) 73 OC12.1 | DOI: 10.1530/endoabs.73.OC12.1

ECE2021 Oral Communications Oral Communications 12: Diabetes, Obesity, Metabolism and Nutrition (6 abstracts)

Prevention of glucocorticoid-induced adipose dysfunction through selective activation of β3-adrenergic signaling in mice

Manuel Gado1, Annett Heinrich1, Denise Wiedersich1, Monique Noll1, Stefan R. Bornstein2, 3, 4, 5, Martina Rauner1, 2, Lorenz C. Hofbauer1, 2, 6 & Holger Henneicke1, 2, 6


1Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany; 2Medizinische Klink III, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 3Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, United Kingdom; 4University Hospital Zurich, Department of Endocrinology and Diabetology, Zurich, Switzerland; 5Paul Langerhans Institute Dresden (PLID) of the Helmholtz Center Munich at Universitätsklinikum Carl Gustav Carus and Faculty of Medicine at Technische Universität Dresden, Dresden, Germany; 6Center for Healthy Aging, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany


Despite their therapeutic effectiveness, glucocorticoids’ (GC) clinical usage is frequently limited due to the deleterious metabolic effects. GC-induced obesity arises from excessive fat accumulation in white adipose tissue (WAT) as well as suppressed thermogenic capacity in brown adipose tissue (BAT). Since the sympathetic nervous system (SNS) plays a fundamental role in adipose tissue biology, we examined the interaction between GCs and SNS signaling in the adipose organ. To that end, we modulated the SNS activity by altering the housing temperature of corticosterone-treated mice and respective controls to either 29°C, 22°C, or 13°C. Following four weeks of corticosterone treatment, mice housed at 29°C and 22°C gained more weight and accumulated more fat than their temperature-matched controls. Interestingly, mice maintained in the 13°C environment were protected from GC-driven weight gain and obesity. Additionally, the cold adaptation of mice effectively protected against GC-induced hyperglycemia, hyperinsulinemia and hyperleptinemia, all of which were readily observed at 29°C and 22°C. Furthermore, the sympathetic innervation as well as the thermogenic capacity of BAT were preserved in mice maintained at 13°C in spite of corticosterone treatment, whereas mice housed at 29°C and 22°C showed a marked reduction in both sympathetic nerve endings and thermogenic capacity following GC exposure. To test whether preservation of sympathetic activity is sufficient to prevent GC-induced dysmetabolism, we co-treated mice with corticosterone and CL-316.243 – a β3-adrenergic agonist. Selective activation of β3-adrenergic receptors not only averted the development of GC-induced fat accumulation and hyperinsulinemia, but also preserved the thermogenic capacity in BAT. Taken together, our data demonstrate that both cold-exposure, as well as β3-adrenergic activation, prevent the onset of GC-induced adipose dysfunction and related metabolic comorbidities. Thus, β3-adrenergic receptors can be considered a potential therapeutic target in the prevention of GC-induced obesity.

Volume 73

European Congress of Endocrinology 2021

Online
22 May 2021 - 26 May 2021

European Society of Endocrinology 

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