Circulating leukocyte cell-derived chemotaxin 2 and fibroblast growth factor 21 are negatively associated with cardiorespiratory fitness in healthy volunteers.

Leukocyte cell-derived chemotaxin-2 (LECT2) and fibroblast growth factor 21 (FGF21) are hepatokines that are regulated by energy balance and mediate insulin sensitivity and glycaemic control. This cross-sectional study examined the independent associations of cardiorespiratory fitness (CRF), moderate-to-vigorous intensity physical activity (MVPA), and sedentary time with circulating LECT2 and FGF21. Data were combined from two previous experimental studies in healthy volunteers (n = 141, male = 60%, mean ± SD age = 37 ± 19 years, body mass index (BMI) = 26.1 ± 6.3 kg·m^-2). Sedentary time and MVPA were measured via an ActiGraph GT3X + accelerometer, while magnetic resonance imaging quantified liver fat. CRF was assessed using incremental treadmill tests. Generalized-linear models examined the association of CRF, sedentary time, and MVPA with LECT2 and FGF21 while controlling for key demographic and anthropometric variables. Interaction terms explored the moderating influence of age, sex, BMI, and CRF. In the fully adjusted models, each SD increase in CRF was independently associated with a 24% (95% CI: -37% to -9%, P = 0.003) lower plasma LECT2 concentration and 53% lower FGF21 concentration (95% CI: -73% to -22%, P = 0.004). Each SD increase in MVPA was independently associated with 55% higher FGF21 (95% CI: 12% to 114%, P = 0.006), and this relationship was stronger in those with lower BMI and higher levels of CRF. These findings demonstrate that CRF and wider activity behaviours may independently modulate the circulating concentrations of hepatokines and thereby influence inter-organ cross-talk.