Metabolically healthy obesity in children and adolescents: A misleading label?

The concept of metabolically healthy obesity (MHO) remains debated, particularly in pediatric populations. Beyond traditional risk factors, evaluating high-density lipoprotein (HDL) functionality may provide further insight into cardiometabolic risk in this population. The aim of this study was to assess cardiometabolic alterations in pediatric MHO, including insulin sensitivity, lipid profile, inflammation, and atheroprotective properties of HDL.

This cross-sectional study included 21 children and adolescents with MHO, 15 with metabolically unhealthy obesity (MUO) and 19 controls. Groups displayed no significant differences in age, sex, and Tanner stage. We measured anthropometrics, insulin resistance [HOMA-IR, QUICKI, non-esterified fatty acids (NEFA)], lipids, systemic and vascular [(lipoprotein-associated phospholipase A₂ (Lp-PLA₂) activity)] inflammation. HDL functionality was assessed by evaluating reverse cholesterol transport [cholesterol efflux capacity (CEC), lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities] and its antioxidant capacity (paraoxonase, arylesterase and inhibition of LDL oxidation). Both MHO and MUO groups exhibited multiple alterations compared to controls, including higher insulin, HOMA-IR, NEFA, LDL-C, and apo B, alongside lower QUICKI, HDL-C, and apo A-I (p < 0.05). Notably, Lp-PLA₂ activity was elevated in both MHO and MUO. While HDL antioxidant capacity was preserved, the main steps of reverse cholesterol transport (CEC and LCAT) were significantly impaired in both groups with obesity.

Children and adolescents with both MHO and MUO exhibit significant metabolic impairments compared with controls. Conventional criteria to define "metabolically healthy" may not capture the full spectrum of cardiometabolic abnormalities. Novel markers of cardiovascular risk could be incorporated into MHO definitions.