Circulating angiopoietin-like protein 8 (ANGPTL8) and ANGPTL3 concentrations in relation to anthropometric and metabolic profiles in Korean children: A prospective cohort study

Background: Previous studies have shown that angiopoietin-like protein 8 (ANGPTL8), also called as betatrophin, acts together with ANGPTL3 to regulate lipid metabolism, glucose metabolism, and energy homeostasis. Moreover, ANGPTL8 promotes proliferation of pancreatic β-cells and induces insulin secretion. However, there are no previous longitudinal studies in humans. Methods: We analyzed the age- and sex-matched data of 240 normal weight and overweight Korean children from the Korean Metabolic disorders and Obesity Study in Elementary School children (K-MOSES), a prospective observational cohort study. Results: At baseline, ANGPTL8 concentrations were positively associated with triglycerides (TG) (r = 0.168, P = 0.010), whereas ANGPTL3 levels were associated with fasting insulin (r = 0.248, P < 0.001) and the homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.197, P = 0.002). Although both ANGPTL8 and ANGPTL3 levels did not differ between children with normal weight and children with overweight, ANGPTL8 levels were increased in males compared to females (341.2 [267.4-436.5] vs. 270.2 [213.9-378.8] pg/ml, P = 0.001). In particular, there was no significant inter-relationship between circulating ANGPTL8 and ANGPTL3 concentrations in Korean boys and girls (r = -0.073, P = 0.265). Multivariate analysis showed that baseline ANGPTL8 concentrations were independently associated with future changes of serum TG levels in Korean children after adjusting for confounding factors after a 3 year follow-up period (r = -0.165, P = 0.016). Conclusions: This longitudinal study demonstrated for the first time that baseline ANGPTL8 levels were associated with baseline and future changes in TG levels in Korean children.