Regulatory T cells and bioenergetics of peripheral blood mononuclear cells linked to pediatric obesity

Shannon Rose; Reid D Landes; Kanan K Vyas; Leanna Delhey; Sarah Blossom

doi:10.1097/IN9.0000000000000040

Regulatory T cells and bioenergetics of peripheral blood mononuclear cells linked to pediatric obesity

Immunometabolism (Cobham). 2024 Apr 25;6(2):e00040. doi: 10.1097/IN9.0000000000000040. eCollection 2024 Apr.

Authors

Shannon Rose^{1

2}, Reid D Landes³, Kanan K Vyas^{1

2}, Leanna Delhey⁴, Sarah Blossom⁵

Affiliations

¹ Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
² Arkansas Children's Research Institute, Little Rock, AR, USA.
³ Department of Biostatistics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
⁴ Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
⁵ Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.

Abstract

Background: Obesity-associated inflammation drives the development of insulin resistance and type 2 diabetes. We sought to identify associations of circulating regulatory T cells (Treg) with the degree of obesity (eg, body mass index Z-score [BMIz]), insulin resistance (homeostatic model of insulin resistance [HOMA-IR]), and glycemic control (HbA1c) in children and adolescents. We further sought to examine associations among bioenergetics of peripheral blood mononuclear cells (PBMCs) and CD4 T cells and BMIz, HOMA-IR, and HbA1c.

Methods: A total of 65 children and adolescents between the ages 5 and 17 years were studied. HbA1c and fasting levels of plasma glucose and insulin were measured. We quantified circulating Tregs (CD3⁺CD4⁺CD25⁺CD127^-FoxP3⁺) by flow cytometry, and measured mitochondrial respiration (oxygen consumption rate [OCR]) and glycolysis (extracellular acidification rate [ECAR]) in PBMCs and isolated CD4 T cells by Seahorse extracellular flux analysis.

Results: Tregs (% CD4) are negatively associated with BMIz but positively associated with HOMA-IR. In PBMCs, OCR/ECAR (a ratio of mitochondrial respiration to glycolysis) is positively associated with BMIz but negatively associated with HbA1c.

Conclusions: In children, Tregs decrease as body mass index increases; however, the metabolic stress and inflammation associated with insulin resistance may induce a compensatory increase in Tregs. The degree of obesity is also associated with a shift away from glycolysis in PBMCs but as HbA1c declines, metabolism shifts back toward glycolysis. Comprehensive metabolic assessment of the immune system is needed to better understand the implications immune cell metabolic alterations in the progression from a healthy insulin-sensitive state toward glucose intolerance in children.

Trial registration: This observational study was registered at the ClinicalTrials.gov (NCT03960333, https://clinicaltrials.gov/study/NCT03960333?term=NCT03960333&rank=1).

Keywords: adolescents; childhood obesity; glucose intolerance; glycolysis; immunometabolism; inflammation; insulin resistance; mTOR.

Associated data

ClinicalTrials.gov/NCT03960333