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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Microbiome and Metabolism Research » Research » Publications at this Location » Publication #427661
Research Project: Early Life Factors and Microbiota Impact on Healthy Development

Location: Microbiome and Metabolism Research

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

Author
item CARVALHO, EUGENIA - University Of Coimbra
item LANDES, REID - University Arkansas For Medical Sciences (UAMS)
item COTTER, MATTHEW - Arkansas Children'S Nutrition Research Center (ACNC)
item DELHEY, LEANNA - University Of Michigan
item BØRSHEIM, ELISABET - Arkansas Children'S Nutrition Research Center (ACNC)
item ROSE, SHANNON - University Of Tennessee

Submitted to: European Journal of Clinical Investigation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/30/2025
Publication Date: 6/17/2025
Citation: Carvalho, E., Landes, R.D., Cotter, M., Delhey, L.M., Børsheim, E., Rose, S. 2025. Enhanced mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) from young children with overweight/obesity and insulin resistance. European Journal of Clinical Investigation. https://doi.org/10.1111/eci.70090.
DOI: https://doi.org/10.1111/eci.70090

Interpretive Summary: The Problem:Insulin resistance, a key factor in the development of type 2 diabetes, often begins in childhood, especially among children with obesity. While previous studies have linked poor mitochondrial function (a process by which our cells produce energy) to insulin resistance in adults, little is known about how this works in children. The Accomplishment:Researchers studied energy-producing activity in immune cells and platelets from young children aged 5 to 10 years. They compared children of normal weight to those with obesity, some of whom already showed signs of insulin resistance. The team discovered that the energy systems in these children's cells adapt in different ways depending on their metabolic health. Notably, children with obesity, even those without insulin resistance, showed changes in how their cells generated energy. These cellular changes were closely linked with measures of whole-body metabolism, such as fat burning and resting metabolic rate. The Contribution:This study is the first to show that easily accessible blood cells can reflect deeper metabolic changes occurring in young children with obesity and insulin resistance.

Technical 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. Methods: We stratified prepubertal children (ages 5–10 years) into three groups: normal weight insulin sensitive (N-IS; n=20), overweight/obese insulin sensitive (O-IS; n=28) and overweight/obese insulin resistant (O-IR; n=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 D2O in urine. We used ANOVA for comparisons among groups and Spearman correlations for associations between circulating cell bioenergetics and whole-body metabolism and biomarkers. 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. 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.