Effect of life course body composition on lipids and coronary atherosclerosis mediated by inflammatory biomarkers

To investigate the mediating role of inflammatory biomarkers in the causal effect of body composition on lipids and atherosclerosis.

Retrospective observational study and Mendelian randomization (MR) study were used. Observational analyses were undertaken using data from 4717 children and adolescents aged 6-18 years from Chinese who underwent dual-energy x-ray absorptiometry for body composition. MR analyses were based on summary statistics from UK Biobank, deCODE2021, GLGC, FinnGen and other large consortiums. Inflammatory biomarkers included leptin, insulin, adiponectin, osteocalcin, fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH).

In retrospective observational study, through osteocalcin, body composition had effects on total cholesterol (TC), triglyceride and low-density lipoprotein cholesterol (LDL). Conversely, fat mass vs. fat-free mass demonstrated opposing effects. Insulin played a role in the association of fat mass with TC and LDL (all P < 0.05). Mediation MR results indicated the causal effect of fat-free mass on coronary atherosclerosis via insulin (indirect effect, OR (odds ratio): 0.95 [95%CI, 0.92-0.98]) and adiponectin (OR: 0.96 [95%CI, 0.93-0.99]). Adiponectin also mediated the causal association of fat mass with coronary heart disease (OR: 1.06 [95%CI, 1.02-1.10]) and coronary atherosclerosis (OR: 1.05 [95%CI, 1.01, 1.09]). Leptin, adiponectin and insulin played roles in mediating the casual effects of body composition on triglyceride and high-density lipoprotein cholesterol.

Our findings suggest different body composition exert varying influences on lipids and atherosclerosis through distinct inflammatory biomarkers. The findings may be helpful in tailoring management of body composition based on inflammatory biomarkers with different lipid profiles.