ESPEYB15 15 Editor’s Choice The importance of being earnest about diurnal variation (1 abstracts)
15.13 A Transcriptional Circuit Filters Oscillating Circadian Hormonal Inputs to Regulate Fat Cell Differentiation
Bahrami-Nejad Z , Zhao ML , Tholen S , Hunerdosse D , Tkach KE , van Schie S , Chung M & Teruel MN
To read the full abstract: Cell Metabolism 2018;27:854-868. e8
People gain weight due to treatment with glucocorticoid (GC) drugs, but also in chronic stress and disrupted circadian rhythms. We now learn that fat-cell maturation increases if the trough in exposure to GC lasts less than 12 hours. A long pulse of glucocorticoids lasting 48 hours led most of the cells to differentiate under the effect of PPAR-gamma, while shorter pulses with at least 12 hours between them resulted in minimal differentiation. They identified FABP4 protein as a key slow positive-feedback regulator of PPAR-gamma. Its feedback loop takes 34 hours activating FABP4, which in return activates PPAR-gamma. Loss of the normal GC circadian rhythm led to a doubling of the animals' fat mass. No increase in fat mass occurred if they boosted GC only during the normal circadian peak times, even when they increased peak GC levels 40-fold. Therefore, stress or GC medication do not cause weight gain, if they only act during the daytime. Conversely, continuous stress, or GC acting at night, such as in the case of Dexamethasone or Prednisone given at bedtime, results in weight gain. Here is another good reason to do our best to simulate the diurnal changes of GC in the treatment of hypocortisolism.
Volume 15
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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