Angiopoietin-Like Protein 8/Leptin Crosstalk Influences Cardiac Mass in Youths With Cardiometabolic Risk: The BCAMS Study

ObjectivesThe link between excess adiposity and left ventricular hypertrophy is multifaceted with sparse data among youths. Given that adipokines/hepatokines may influence lipid metabolism in myocardium, we aimed to investigate the relation of the novel hepatokine angiopoietin-like protein 8 (ANGPTL8) and other adipokines with cardiac structure in a cohort of youths and explore to what extent these adipokines/hepatokines affect cardiac structure through lipids. MethodsA total of 551 participants (aged 15-28 years) from the Beijing Child and Adolescent Metabolic Syndrome Study (BCAMS) cohort underwent echocardiographic measurements plus a blood draw assayed for five adipokines/hepatokines including adiponectin, leptin, retinol binding protein 4, fibroblast growth protein 21 and ANGPTL8. ResultsBoth ANGPTL8 (beta = -0.68 g/m(2.7) per z-score, P= 0.015) and leptin (beta = -1.04 g/m(2.7) per z-score, P= 0.036) were significantly inversely associated with left ventricular mass index (LVMI) independent of classical risk factors. Total cholesterol and low-density lipoprotein cholesterol significantly mediated the ANGPTL8-LVMI association (proportion: 19.0% and 17.1%, respectively), while the mediation effect of triglyceride on the ANGPTL8-LVMI relationship was strongly moderated by leptin levels, significantly accounting for 20% of the total effect among participants with higher leptin levels. Other adipokines/hepatokines showed no significant association with LVMI after adjustment for body mass index. ConclusionsOur findings suggest ANGPTL8, particularly interacting with leptin, might have a protective role in cardiac remodeling among youths with risk for metabolic syndrome. Our results offer insights into the pathogenesis of the cardiomyopathy and the potential importance of tissue-tissue crosstalk in these effects.

Automated summary

This study aimed to investigate the relationship between ANGPTL8 and other adipokines with cardiac structure in youths, and to explore the role of lipids in mediating this relationship. The findings showed a significant inverse association between ANGPTL8 and leptin with left ventricular mass index (LVMI), independent of risk factors. Total cholesterol and low-density lipoprotein cholesterol mediated the ANGPTL8-LVMI association, while triglyceride mediation was moderated by leptin levels. Other adipokines showed no significant association with LVMI.