Mineralocorticoid antagonism enhances brown adipose tissue function in humans: A randomized placebo-controlled cross-over study.

AIM: To investigate whether mineralocorticoid (MC) antagonism enhances brown adipose tissue (BAT) function in humans. MATERIALS AND METHODS: In a randomized double-blind, cross-over designed trial, 10 healthy adults (two men, eight women) underwent 2 weeks of spironolactone (100 mg/d) treatment and placebo, with an intervening 2-week wash-out period. BAT function was assessed in response to cooling and to a mixed meal. Metabolic activity was measured by fluoro-deoxyglucose (FDG) uptake (maximal standardized uptake value, SUVmax ) using PET-CT. Thermogenic activity was measured by skin temperatures overlying supraclavicular (SCL) BAT depots using infrared thermography. Postprandial metabolism was measured by energy production rate (EPR) and lipid synthesis using indirect calorimetry. RESULTS: During cooling, BAT metabolic activity (SUV 6.30 ± 2.16 vs 3.98 ± 1.34; P < 0.05) and volume (54.9 ± 22.8 vs 21.6 ± 11.8 cm3 ; P < 0.05) were significantly higher, and mean SCL temperature decreased by a smaller degree (-0.3°C°± 0.2°C vs -0.9°C ± 0.2°C; P = 0.05) with spironolactone treatment. A mixed meal increased SCL temperature and EPR. The postprandial rise in SCL temperature (+0.4°C ± 0.1°C vs +0.1°C ± 0.1°C; P < 0.05) but not in EPR was greater during spironolactone treatment. Postprandial lipid synthesis occurred in three participants with placebo but in none with spironolactone treatment (P = 0.06). CONCLUSION: MC antagonism enhanced human BAT function in response to cooling and to a meal during which lipid synthesis was suppressed. As postprandial EPR comprises energy dissipated as heat and energy required to store nutrients, the reduction in lipid synthesis during MC antagonism is a probable consequence of concurrent stimulation of BAT thermogenesis. The shift in energy usage from storage to heat dissipation indicates that MC antagonists may have therapeutic benefit for obesity.

Glucocorticoids suppress brown adipose tissue function in humans: A double-blind placebo-controlled study.

AIM: To investigate the effect of glucocorticoids on brown adipose tissue (BAT) function in humans. MATERIALS AND METHODS: In a randomized double-blind cross-over design, 13 healthy adults underwent 1 week of oral prednisolone treatment (15 mg/d) and placebo with an intervening 2-week wash-out period. BAT function was assessed in response to cooling (19°C) and to a standardized meal, by measuring fluoro-deoxyglucose (FDG) uptake using positron emission tomography-computed tomography and skin temperatures overlying the supraclavicular (SCL) BAT depots using infrared thermography. Postprandial energy and substrate metabolism was assessed by indirect calorimetry. RESULTS: During cooling, prednisolone significantly reduced BAT FDG uptake (standardized uptake value, SUVmax, 6.1 ± 2.2 vs 3.7 ± 1.2; P < .05) and SCL temperature (-0.45 ± 0.1 vs -1.0 ± 0.1°C; P < .01) compared to placebo. Postprandially, prednisolone significantly blunted the rise in SCL temperature (+0.2 ± 0.1 vs -0.3 ± 0.1°C; P < .05), enhanced energy production (+221 ± 17 vs +283 ± 27 kcal/d; P < .01) and lipid synthesis (+16.3 ± 3.2 vs +23.6 ± 4.9 mg/min; P < .05). The prednisolone-induced reduction in SCL temperature significantly correlated with the reduction in FDG uptake (r = 0.65, P < .05), while the increase in energy production significantly correlated with the increase in lipogenesis (r = 0.6, P < .05). CONCLUSION: Prolonged exposure to glucocorticoid suppresses the function of human BAT. The enhancement of energy production and lipogenesis in the face of reduced dissipation of energy as heat suggests that glucocorticoids channel energy towards fat storage after nutrient intake. This is a novel mechanism of glucocorticoid-induced obesity.