Background: Brown adipose tissue (BAT) dissipates nutrient energy as heat and is metabolically significant. In rodents, BAT is regulated by mineralocorticoids (MC); MC excess suppresses BAT function while MC blockade recruits BAT and prevents diet-induced obesity.
Aim: To investigate the effect of MC blockade on human BAT.
Method: In a randomised double-blind cross-over design, 10 healthy adults (2 men, 8 women; mean±SEM age 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 intervening 2-week wash-out. After each treatment, BAT function was assessed, under standardised cooling (190C), by measuring BAT metabolic activity and volume on FDG-PET-CT, and skin temperatures overlying the supraclavicular (SCL) BAT depots by infrared thermography. Energy and substrate metabolism was assessed 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<0.05) and volume (21.6±11.8 vs 54.9±22.8cm3; P<0.05) were higher with spironolactone. Mean SCL temperature fell by a lesser degree after cooling (-0.9±0.2 vs -0.3±0.20C; P=0.05), and rose by a higher degree postprandially (+0.1±0.1 vs +0.4±0.10C; P<0.05) with spironolactone. Meal-stimulated energy production (245±24 vs 219±34kcal/day; P=0.5) was not different between the treatments. Lipid synthesis occurred in 3 subjects postprandially during placebo but in none during spironolactone treatment (P=0.06).
Summary: Spironolactone increased BAT metabolic activity, volume and thermogenic response to cold. After a meal, it did not affect total energy production, but increased BAT thermogenesis and tended to reduce lipid synthesis.
Conclusion: MC blockade recruits BAT in humans, and may suppress postprandial lipogenesis. 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.