Enhanced mitochondrial respiration in peripheral blood mononuclear cells () from young children with overweight/obesity and insulin resistance

Abstract

Abstract Background Studies implicating dysfunctional mitochondrial respiration in metabolic tissues in the development of insulin resistance in obesity have only included adults. Peripheral blood mononuclear cells (PBMCs) and platelets have been found to reflect systemic mitochondrial fitness and bioenergetic health. We sought to identify bioenergetic differences in PBMCs and platelets from children with obesity and insulin resistance and determine associations with whole‐body metabolism and/or biomarkers of metabolic health and inflammation. eci70090-sec-0001 Methods We stratified prepubertal children (ages 5–10 years) into three groups: normal weight insulin sensitive (N‐IS;= 20), overweight/obese insulin sensitive (O‐IS;= 28) and overweight/obese insulin resistant (O‐IR;= 17). We measured oxygen consumption rate and proton efflux rate in PBMCs and platelets. We estimated whole‐body resting metabolic rate by bioimpedance and dietary fatty acid oxidation by oral deuterated palmitate and quantifying recovery of DO in urine. We used ANOVA for comparisons among groups and Spearman correlations for associations between circulating cell bioenergetics and whole‐body metabolism and biomarkers. eci70090-sec-0002 Results O‐IS and O‐IR PBMCs exhibited increased maximal mitochondrial respiration and spare respiratory capacity compared to N‐IS. Bioenergetics shifted towards glycolysis in O‐IS PBMCs as compared to both N‐IS and O‐IR PBMCs. In platelets, glycolysis and ATP production rates were decreased in O‐IR compared to O‐IS children. PBMC respiration positively correlated with BMIz, HOMA‐IR and fasting glucose and insulin, but negatively correlated with inflammatory cytokines. Dietary fatty acid oxidation was higher in O‐IS compared to N‐IS children and positively correlated with PBMC spare respiratory capacity. Resting metabolic rate correlated positively with several parameters of PBMC mitochondrial respiration. eci70090-sec-0003 Conclusions PBMCs from young children with overweight/obesity exhibit adaptations to the metabolic stressors associated with insulin resistance, and PBMC metabolism correlates well with whole‐body metabolism. eci70090-sec-0004 We investigated measures of mitochondrial function in certain types of blood cells and metabolism in 65 children, 5–10 years old. Compared to children of normal weight (= 20), children with overweight/obesity (= 28) and especially those with insulin resistance (= 17), differed in how their cells produced energy. Differences were linked with body fat, blood glucose and inflammation. This suggests that blood cell metabolism may reflect whole‐body health and help identify early signs of metabolic disease in kids. Created in BioRender. Borsheim, E. (2025). graphical