Effect of high-dose glucocorticoid treatment on human brown adipose tissue activity: a randomised, double-blinded, placebo-controlled cross-over trial in healthy men
Abstract
Background Glucocorticoids (GCs) are widely applied anti-inflammatory drugs that are associated with adverse metabolic effects including insulin resistance and weight gain. Previous research indicates that GCs may negatively impact brown adipose tissue (BAT) activity in rodents and humans.Methods We performed a randomised, double-blinded cross-over trial in 16 healthy men (clinicaltrials.gov NCT03269747). Participants received 40 mg of prednisone per day for one week or placebo. After a washout period of four weeks, participants crossed-over to the other treatment arm. Primary endpoint was the increase in resting energy expenditure (EE) in response to a mild-cold stimulus (cold-induced thermogenesis, CIT). Secondary outcomes comprised mean 18F-FDG uptake into supraclavicular BAT (SUVmean) as determined by FDG-PET/CT, volume of the BAT depot as well as fat content determined by MRI. The plasma metabolome and the transcriptome of supraclavicular BAT and of skeletal muscle biopsies after each treatment period were analysed.Findings Sixteen participants were recruited to the trial and completed it successfully per protocol. After prednisone treatment resting EE was higher both during warm and cold conditions. However, CIT was similar, 153 kcal/24 h (95% CI 40-266 kcal/24 h) after placebo and 186 kcal/24 h (95% CI 94-277 kcal/24 h, p = 0.38) after prednisone. SUVmean of BAT after cold exposure was not significantly affected by prednisone (3.36 g/ml, 95% CI 2.69-4.02 g/ml, vs 3.07 g/ml, 95% CI 2.52-3.62 g/ml, p = 0.28). Results of plasma metabolomics and BAT transcriptomics corroborated these findings. RNA sequencing of muscle biopsies revealed higher expression of genes involved in calcium cycling. No serious adverse events were reported and adverse events were evenly distributed between the two treatments.Interpretation Prednisone increased EE in healthy men possibly by altering skeletal muscle calcium cycling. Cold induced BAT activity was not affected by GC treatment, which indicates that the unfavourable metabolic effects of GCs are independent from thermogenic adipocytes. Show more
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https://doi.org/10.3929/ethz-b-000636596Publication status
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eBioMedicineVolume
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ElsevierSubject
Brown adipose tissue; Cold-induced thermogenesis; Glucocorticoids; Prednisone; Energy expenditure; cold-induced brown adipose tissue (BAT) thermogenesis. TwoOrganisational unit
08839 - Zamboni, Nicola (Tit.-Prof.)
03819 - Wolfrum, Christian / Wolfrum, Christian
03819 - Wolfrum, Christian / Wolfrum, Christian
02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich
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