Neurological‐related proteomic profiling in plasma of children with metabolic healthy and unhealthy overweight/obesity

OBJECTIVE: Children with overweight/obesity (OW/OB) exhibit poor cardiometabolic health, yet mechanisms influencing brain health remain unclear. We examined the differences in neurological-related circulating proteins in plasma among children with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) and the association with metabolic syndrome markers. METHODS: In this cross-sectional study, we included 84 Caucasian children (39% girls), aged 10.1 ± 1.1 years, from the ActiveBrains project (NCT02295072). A ninety-two-protein targeted approach using Olink's® technology was used. RESULTS: We identified distinct concentrations of CD38, LAIR2, MANF and NRP2 proteins in MHO compared with MUO. Moreover, individual metabolic syndrome (MS) markers were linked to nine proteins (CD38, CPM, EDA2R, IL12, JAMB, KYNU, LAYN, MSR1 and SMOC2) in children with OW/OB. These proteins play crucial roles in diverse biological processes (e.g., angiogenesis, cholesterol transport, nicotinamide adenine dinucleotide (NAD+) catalysis and maintenance of blood-brain barrier) related to brain health. CONCLUSION: Our proteomics study suggests that cardiometabolic health (represented by MHO/MUO or individual MS markers) is associated with the concentration in plasma of several proteins involved in brain health. Larger-scale studies are needed to contrast/confirm these findings, with CD38 standing out as a particularly noteworthy and robust discovery.