Effect of Mineralocorticoid Blockade on Human Brown Fat – a Randomised Placebo-Controlled Cross-over Study
Presentation Number: LB SUN 66
Date of Presentation: April 2nd, 2017
Moe Thuzar*1, W Phillip Law2, Goce Dimeski2, Michael Stowasser3 and Ken Ho4
1Princess Alexandra Hospital/ University of Queensland, Woolloongabba, Australia, 2Princess Alexandra Hospital, Woolloongabba, Australia, 3University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Brisbane, Australia, 4Princess Alexandra Hospital/ University of Queensland, Brisbane, Australia
Background: Brown adipose tissue (BAT) dissipates nutrient energy as heat and is metabolically significant. There is evidence that BAT may be regulated by mineralocorticoids (MC). In rodents, MC excess suppresses BAT function while MC blockade increases BAT mass and prevents diet-induced obesity.
Aim: To investigate whether MC blockade enhances BAT function in humans.
Method: In a randomised double-blind cross-over design, 10 healthy adults (2 men, 8 women; age mean±SEM, 28±1 year; BMI 24.4±1.2 kg/m2) underwent 2 weeks each of oral spironolactone (MC receptor antagonist) (100mg/day) and placebo treatments with an intervening 2-week wash-out. After each treatment, under standardised cooling (190C), BAT function was assessed by measuring (i) BAT metabolic activity and BAT volume by fluoro-deoxy-glucose (FDG)-PET-CT scan (ii) skin temperatures overlying the supraclavicular (SCL) BAT depots by infrared thermography and (iii) energy production and substrate metabolism after a standardised meal using indirect calorimetry.
Results: Compared to placebo, BAT metabolic activity (standardised uptake value SUVmax 3.98±1.34 vs 6.3±2.16; P=0.04) and volume (21.6±11.8 vs 54.9±22.8 cm3; P=0.047) were significantly higher after spironolactone treatment. Over 2 hours of cooling, SCL temperature fell by a lower degree during spironolactone treatment (-0.9±0.2 vs -0.3±0.20C; P=0.05). After the meal, SCL temperature rose by a significantly higher degree during spironolactone treatment (+0.1±0.1 vs +0.4±0.10C; P=0.03). There was no difference in meal-stimulated energy production (245±24 vs 219±34 kcal/day; P=0.5) between the two treatments. Lipid synthesis occurred in 3 subjects after the meal during placebo but in none during spironolactone treatment (P=0.06).
Summary: Spironolactone treatment increased BAT metabolic activity, volume and thermogenic response to cold. It did not change total energy production, but increased BAT thermogenesis and tended to reduce lipid synthesis in response to a meal.
Conclusion: MC blockade enhances BAT function in humans, and may suppress postprandial lipid synthesis. As energy production after a meal is the sum of energy dissipated as heat and that channelled for storage, the findings suggest that MC blockade diverts nutrient energy from storage towards dissipation as heat. MC blockade may be a potential treatment for obesity.
Nothing to Disclose: MT, WPL, GD, MS, KH