The principal findings of the present study were that measures of adiposity (including BMI, sum of skinfolds and waist circumference) and physical fitness (measured by performance on the multi-stage fitness test) were both important, and additive, predictors of novel risk factors for cardiovascular disease (pro-inflammatory cytokine TNF-α and anti-inflammatory cytokine IL-10), blood pressure and metabolic health markers (plasma insulin concentration and HOMA-IR) across adolescence. The gene discussed is TNF; the disease is cardiovascular disorder.