Regulatory T cells and bioenergetics of peripheral blood mononuclear cells linked to pediatric obesity-Immunometabolism-CSCIED科技核心评价数据库-手机版

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

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

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DOI	10.1097/IN9.0000000000000040
刊名	Immunometabolism IJ
年，卷(期)	2024, 6(2)
作者	Rose, Shannon; Landes, Reid D.; Vyas, Kanan K.; Delhey, Leanna; Blossom, Sarah,
作者单位	[Rose, Shannon; Vyas, Kanan K.] Univ Arkansas Med Sci, Coll Med, Dept Pediat, Little Rock, AR 72202 USA; [Rose, Shannon; Vyas, Kanan K.] Arkansas Childrens Res Inst, Little Rock, AR 72202 USA; [Landes, Reid D.] Univ Arkansas Med Sci, Coll Med, Dept Biosta
摘要	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).
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).
关键词	adolescents; childhood obesity; glucose intolerance; glycolysis; immunometabolism; inflammation; insulin resistance; mTOR
KeyWord	adolescents; childhood obesity; glucose intolerance; glycolysis; immunometabolism; inflammation; insulin resistance; mTOR
基金项目
页码	1-8

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引用本文

Rose, Shannon; Landes, Reid D.; Vyas, Kanan K.; Delhey, Leanna; Blossom, Sarah. Regulatory T cells and bioenergetics of peripheral blood mononuclear cells linked to pediatric obesity [J]. Immunometabolism. 2024; 6; (2). 1 - 8.

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