To investigate whether mineralocorticoid (MC) antagonism enhances brown adipose tissue (BAT) function in humans.
In a randomized double-blind cross-over design, 10 healthy adults (2 men, 8 women) underwent two weeks of spironolactone (100mg/day) and placebo treatments with an intervening 2-week wash-out. 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 by measuring skin temperatures overlying supraclavicular (SCL) BAT depots using infrared thermography, and postprandial metabolism by measuring energy production rate (EPR) and lipid synthesis using indirect calorimetry.
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 fell by a smaller degree (-0.3±0.2 vs -0.9±0.20 C; P=0.05) with spironolactone treatment. A mixed meal increased SCL temperature and EPR. The postprandial rise in SCL temperature (+0.4±0.1 vs +0.1±0.10 C; P<0.05) but not EPR was greater during spironolactone treatment. Postprandial lipid synthesis occurred in three subjects during placebo but none during spironolactone treatment (P=0.06).
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 likely consequence of concurrent stimulation of BAT thermogenesis. The shift of energy usage from storage to heat dissipation indicates that MC antagonists may have therapeutic benefit for obesity. This article is protected by copyright. All rights reserved.