Circulating succinate changes during acute cold exposure are not related with brown adipose tissue in humans

Brown adipose tissue (BAT) activity in humans is linked to better glucose metabolism and cardiometabolic health. In mice, cold exposure increases circulating succinate and enhances BAT thermogenesis, but whether similar succinate responses occur in humans remains undetermined. We analysed data from 33 young (18-25 years), sedentary adults (20 women) from the ACTIBATE cohort (NCT02365129). Plasma succinate was measured enzymatically at baseline and 60 and 120 min during a personalized cooling protocol. BAT volume, activity, and radiodensity were assessed via static ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (¹⁸F-FDG PET-CT) at the end of the cold exposure. Circulating succinate changed over time during cold exposure, with no significant change at 60 min and a significant increase at 120 min versus baseline (+ 23.8%, P = 0.017), with substantial interindividual variability. Exploratory stratification by median baseline succinate revealed divergent temporal patterns: the low-baseline group showed increases at 60 min (+ 46%) and 120 min (+ 80.5%; both P ≤ 0.021), while the high-baseline group showed reductions at both timepoints (-31.4% and - 2.4%; both P ≤ 0.003). These profiles were not explained by phenotypic or BAT-related parameters. In the full cohort, changes in circulating succinate were not associated with BAT outcomes. Overall, our findings indicate that circulating succinate responses during acute cold exposure are highly heterogeneous and no associated with BAT PET/CT-derived parameters in humans.