Endocrine Abstracts

Introduction: Brown adipose tissue (BAT) increases energy expenditure and is a potential therapeutic target for obesity and associated cardiometabolic disease. It is unclear whether human BAT activity is reduced in obesity, as BAT ¹⁸F-fluorodeoxyglucose uptake is reduced but BAT metabolic activity measured using¹¹C-acetate PET is preserved. BAT thermogenesis relies on the presence of uncoupling protein 1 (UCP1), which uncouples oxidative phosphorylation from ATP synthesis. We hypothesized that BAT UCP1 levels are reduced in individuals with cardiometabolic disease.

Methods: BAT and WAT samples were obtained from 141 patients undergoing elective neck surgery. UCP1 mRNA levels were measured by quantitative real-time PCR in whole tissue (n=53) and differentiated pre-adipocytes (n=88). We tested whether UCP1 levels in whole tissue/adipocytes were associated with important cardiometabolic risk factors.

Results: Individuals with high UCP1 levels in whole BAT (threshold >2AU) were younger (44.1±14.4y vs 55.7±11.7y) with lower body mass index (26.5±4.9 kg/m² vs 30.1±6.0 kg/m²), waist circumference (84.8±19.1 cm vs 99.3±18.6 cm), waist-hip ratio (0.86±0.06 vs 0.92±0.08), fat percentage (20.9±9.1% vs 28.8±11.4%), systolic (131±25 mMHg vs 143±22 mMHg) and diastolic blood pressure (79±12 mMHg vs 86±11 mMHg). BAT UCP1 levels were lower in subjects with pre-existing hypertension and those prescribed beta-blockers. BAT (but not WAT) UCP1 levels correlated negatively with age (r=-0.309), weight (r=-0.321), waist circumference (r=-0.315) and fat mass (r=-0.242). However, UCP1 levels in differentiated brown adipocytes were not associated with any of the above measurements.

Conclusion: BAT UCP1 levels are decreased in older, obese and hypertensive subjects, consistent with defective BAT thermogenesis. However, these subjects retain brown pre-adipocytes with the capacity to form new thermogenic adipocytes during appropriate stimulation. These data highlight the therapeutic potential of increasing BAT mass and activity in this patient group as a therapeutic strategy to ameliorate the metabolic consequences of obesity.