Mitochondrial oxidative capacity and function in human white, beige and brown adipose tissue (1160.6)

Abstract

Our understanding of mitochondrial oxidative capacity (oxphos) and function in brown adipose tissue (BAT) is derived from cell and murine models. Here, we determined mitochondrial oxphos and function in white adipose tissue from healthy individuals (WAT, n=9), beige adipose tissue from severely burned children (BeAT, n=8), and BAT from healthy individuals (n=3). Mitochondrial respiration was determined following the addition of 1) substrates; 2) ADP; 3) succinate; and 4) oligomycin. Thereafter, the ratios of coupled to leak and uncoupled to coupled respiration were calculated. Oxphos was higher in BAT (14.3±6.1 pmol/mg/sec; P<0.001) vs. both WAT (1.1±0.2 pmol/mg/sec) and BeAT (2.8±0.4 pmol/mg/sec). Oxphos was also significantly higher in BeAT vs. WAT (P<0.001). The ratio of coupled/leak respiration was lower in BAT vs. WAT and BeAT (P<0.01), whereas the ratio of uncoupled/coupled respiration was higher BAT and BeAT vs. WAT (P<0.05). BAT and BeAT are similar with regards to oligomycin sensitivity, suggesting a more thermogenic phenotype than WAT. However, as oxphos is higher and ADP sensitivity lower in BAT vs. BeAT, suggests that BAT is functionally distinct from BeAT in humans.Grant Funding Source: Supported by NIH (P50‐GM60338, RO1‐GM05668), NIDRR (H133P110012) and SHC (84090, 84080) grants