Chronic ephedrine administration decreases brown adipose tissue activity in a randomised controlled human trial: implications for obesity
Document TypeMasters Research thesis
Access StatusOpen Access
© 2018 Renata Pajtak
Aim Activation of Brown Adipose Tissue (BAT) may have therapeutic potential to combat obesity. Acute treatment of mice with sympathomimetic drugs activates BAT thermogenesis, and chronic treatment increases BAT thermogenic capacity. It has previously been demonstrated that human BAT is acutely responsive to oral administration of the sympathomimetic ephedrine. This study aimed to determine whether chronic treatment with ephedrine could mimic adaptive thermogenesis in humans. Methods Twenty-three healthy young men were recruited via general advertisement from Melbourne, Australia to participate in a randomised, placebo-controlled, parallel group trial. Recruited individuals were unmedicated, non-smokers, physically inactive and had no prior history of either cardiovascular disease, insulin resistance or diabetes. They were allocated to either a placebo (n=11; 22±2 years, 23±2 kg/m2) or 1.5 mg/kg/day ephedrine (active group; n=12, age 23±1 years, BMI 24±1 kg/m2) treatment group for twenty-eight days. Body composition was measured before and after the intervention by dual energy x-ray absorptiometry. BAT activity, measured before and after the twenty-eight day intervention period, via 18F-fluorodeoxyglucose positron emission tomography computed-tomography (18F-FDG PET/CT) in response to a single dose of 2.5mg/kg ephedrine, was the primary outcome measure. Results After twenty-eight days of treatment, the active treatment lost significantly more total body fat (placebo 1.1± 0.3 kg, ephedrine -0.9 ± 0.5kg; p<0.01) and visceral adipose tissue (placebo 6.4 ± 19.1g, ephedrine -134 ± 43g; p<0.01), with no change in lean mass or bone mineral content, compared with the placebo group. In response to acute ephedrine, BAT activity (change in mean standardised uptake value: placebo -3 ± 7 %, ephedrine -22 ± 6%) and the increase in systolic blood pressure were significantly reduced (p<0.05) in the active group compared with placebo. Conclusion Chronic ephedrine treatment reduced body fat content, however, it was independent of an increase in BAT activity. Rather, chronic ephedrine treatment suppressed BAT glucose disposal, suggesting that chronic ephedrine treatment decreased, rather than increased BAT activity.
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- Physiology - Theses