Context: Inflammation has been associated with atherosclerosis and metabolic disorders in youth. Preventing inflammation through exposure to different accelerometer-based movement behaviors has not been longitudinally examined.

Objective: This work aimed to examine the mediating role of fat mass, lipids, and insulin resistance on the associations of cumulative sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) with inflammation.

Methods: From the Avon Longitudinal Study of Parents and Children, United Kingdom, 792 children with data on at least 2 time-point measures of accelerometer-based ST, LPA, and MVPA during age 11, 15, and 24 years follow-up clinic visits with complete high-sensitivity C-reactive protein (hsCRP) measures at age 15, 17, and 24 years were studied. Mediating associations were examined using structural equation models. When the magnitude of the association between the exposure and outcome is increased after including a third variable, suppression occurred but mediation if decreased.

Results: Among 792 (58% female; mean [SD] age at baseline, 11.7 [0.2] years), ST increased, LPA decreased, and MVPA had a U-shaped increase while hsCRP increased during 13-year follow-up. Insulin resistance partly suppressed (23.5% suppression) the positive associations of ST with hsCRP among participants who were overweight/obese. Fat mass partly mediated (30% mediation) the negative associations of LPA with hsCRP. Fat mass had a 77% mediation effect on the negative associations of MVPA with hsCRP.

Conclusion: ST worsens inflammation, but increased LPA had a 2-fold inflammatory-lowering effect and was more resistant to the attenuating effect of fat mass compared with MVPA, and hence should be targeted in future interventions.