Regulatory T cells and bioenergetics of peripheral blood mononuclear cells linked to pediatric obesity. 2024

Shannon Rose, and Reid D Landes, and Kanan K Vyas, and Leanna Delhey, and Sarah Blossom
Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

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

UI MeSH Term Description Entries

Related Publications

Shannon Rose, and Reid D Landes, and Kanan K Vyas, and Leanna Delhey, and Sarah Blossom
July 1985, Gut,
Shannon Rose, and Reid D Landes, and Kanan K Vyas, and Leanna Delhey, and Sarah Blossom
April 2022, Biopreservation and biobanking,
Shannon Rose, and Reid D Landes, and Kanan K Vyas, and Leanna Delhey, and Sarah Blossom
February 2010, Journal of immunological methods,
Shannon Rose, and Reid D Landes, and Kanan K Vyas, and Leanna Delhey, and Sarah Blossom
May 2005, Transplantation,
Shannon Rose, and Reid D Landes, and Kanan K Vyas, and Leanna Delhey, and Sarah Blossom
June 2020, Scientific reports,
Shannon Rose, and Reid D Landes, and Kanan K Vyas, and Leanna Delhey, and Sarah Blossom
June 2007, Biochemical and biophysical research communications,
Shannon Rose, and Reid D Landes, and Kanan K Vyas, and Leanna Delhey, and Sarah Blossom
January 2022, Translational medicine communications,
Shannon Rose, and Reid D Landes, and Kanan K Vyas, and Leanna Delhey, and Sarah Blossom
February 2019, Comparative immunology, microbiology and infectious diseases,
Shannon Rose, and Reid D Landes, and Kanan K Vyas, and Leanna Delhey, and Sarah Blossom
December 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,
Shannon Rose, and Reid D Landes, and Kanan K Vyas, and Leanna Delhey, and Sarah Blossom
October 2012, Investigative ophthalmology & visual science,
Copied contents to your clipboard!