The influence of adiposity and acute exercise on circulating hepatokines in normal 1 weight and overweight/obese men 2

40 Hepatokines are liver-secreted proteins with potential to influence glucose regulation and 41 other metabolic parameters. This study investigated differences in adiposity status on five 42 novel hepatokines and characterised their response to acute moderate-intensity exercise in 43 groups of normal weight and overweight/obese men. 44 Twenty-two men were recruited into normal weight and overweight/obese groups (BMI: 18.5 45 to 24.9 and 25.0 to 34.9 kg∙m -2 ). Each completed two experimental trials, exercise and control. 46 During exercise trials, participants performed 60 min of moderate-intensity treadmill exercise 47 (~60% V̇ O 2 peak) and then rested for 6 h. Participants rested throughout control trials. 48 Circulating fibroblast growth factor-21 (FGF21), follistatin, leukocyte cell-derived 49 chemotaxin 2 (LECT2), fetuin-A and selenoprotein-P (SeP) were measured throughout. 50 Fasted (resting) FGF21 and LECT2 were higher in overweight/obese individuals (129% and 51 55%; P ≤ 0.01) and correlated with indices of adiposity and insulin resistance; whereas 52 circulating follistatin was lower in overweight/obese individuals throughout trial days (17%, 53 P < 0.05). In both groups, circulating concentrations of FGF21 and follistatin were transiently 54 elevated after exercise for up to 6 h ( P ≤ 0.02). Circulating fetuin-A and SeP were no 55 different between groups ( P ≥ 0.19) and, along with LECT2, were unaffected by exercise ( P 56 ≥ 0.06). 57 These findings show that increased adiposity is associated with a modified hepatokine profile, 58 which may represent a novel mechanism linking excess adiposity to metabolic health. Furthermore, acute perturbations in circulating FGF21 and follistatin after exercise may contribute to the health benefits of an active lifestyle.