ECE2020 Audio ePoster Presentations Diabetes, Obesity, Metabolism and Nutrition (285 abstracts)
Association between the circadian rhythm and the inhibitory effect of glucocorticoids on browning of adipocytes
Noemi Congiusta 1 , Iacopo Gesmundo 1 , Mariarosaria Negri 2 , Pasquale Pagliaro 3 , Rosario Pivonello 2 , Claudia Penna 3 , Ezio Ghigo 1 & Riccarda Granata 1
1Division of Endocrinology, Diabetes and Metabolism, University of Torino, Medical science, Turin, Italy; 2Federico II university, Clinical Medicine and Surgery, Napoli, Italy; 3University of Turin, Clinical and Biological Sciences, Torino, Italy
White adipose tissue (WAT) stores excess energy as triglycerides, while brown adipose tissue (BAT) dissipates energy through heat, acting as a defense against cold and obesity and as a positive regulator of metabolic functions. The thermogenic function of BAT is mainly regulated by the mitochondrial uncoupling protein 1 (UCP1) in brown adipocytes. Moreover, it has been shown that chronic exposure to glucocorticoids (GC) or synthetic GC receptor (GR) agonists inhibits the activity of brown adipocytes and browning of WAT. Despite the broad literature on the regulation of BAT function and body temperature, little is known on the mechanisms controlling circadian thermogenic rhythms and, more importantly, how this pattern is affected by GC. Thus, aim of this study was to assess the impact of GC on browning of 3T3-L1 adipocytes and on the association with expression of clock genes. 3T3-L1 adipocytes were transdifferentiated into brown adipocytes, then synchronized by serum shock before mRNA analysis of UCP-1 and clock genes. The increase in UCP-1 mRNA substantiated the transdifferentiation into brown adipocytes. Moreover, clock gene expression analysis confirmed the rhythmic regulation of 3T3-L1 adipocytes after serum shock synchronization, with a peak of mRNA expression at 4 h (indicated as Zeitgeber time 4, ZT4) for Clock and Bmal1 (light phase genes), and a peak at ZT16 for Rev-erbα and Rev-erbβ (dark phase genes). Administration of the GR-agonist dexamethasone (Dexa) to transdifferentiating adipocytes increased the mRNA expression of brown genes (UCP-1, Tmem26, CD137 and Cidea) at ZT16, whereas their levels were reduced at ZT4 and ZT10. These preliminary findings suggest that, depending on the time of the day, treatment with GC may have a different impact on metabolism, such as browning of adipocytes and the metabolic functions of both white and brown adipocytes.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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