Insulin Resistance in Obese Children: What Can Metabolomics and Adipokine Modelling Contribute?
Abstract
:1. Introduction
2. Childhood Obesity and the Development of Insulin Resistance
2.1. Childhood Obesity
2.2. Adipose Tissue in Obesity: The Importance of Age at Onset
2.3. Adipokines in Childhood Obesity
2.4. Carbohydrate Metabolism Impairment in Childhood Obesity: Insulin Resistance
3. Adipokine Modelling
4. Metabolomics
4.1. Untargeted Metabolomics
4.2. Untargeted Metabolomics Applied to Obesity and Insulin Resistance in Children and Adolescents
4.3. Semi-Targeted Metabolomics
4.4. Semi-Targeted Metabolomics Applied to Obesity and Insulin Resistance in Children and Adolescents
4.5. Targeted Metabolomics
4.6. Targeted Metabolomics Applied to Obesity and Insulin Resistance in Children and Adolescents
4.7. Combining Metabolomics Information in Obesity and Insulin Resistance
Methodology | Instrumental Analysis | Disease | Study Design | Sample | Findings | Ref. |
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Untargeted | LC-MS, CE-MS, GC-MS | Obesity and IR | Fingerprinting study: 60 prepubertal obese children. Boys (n = 30, 50% IR and 50% non-IR) Girls (n = 30, 50% IR and 50% non-IR) Validation study: 100 prepubertal obese children. Boys (n = 50, 50% IR and 50% non-IR) Girls (n = 50, 50% IR and 50% non-IR) | Serum | IR vs non-IR: | [51] |
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Untargeted | LC-MS/MS | Metabolic Risk | Boys (n = 113) Girls (n = 125) (8–14 years) | Serum | Metabolic Risk: In girls: | [54] |
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In boys:: | ||||||
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Untargeted | NMR | IR | Cross sectional study: 78 non diabetic adolescents (8–18 years) Longitudinal study: 16 subjects after a mean follow-up of 2.3 years | Plasma | Higher baseline 2-hydroxybutyrate and BCAA levels in insulin resistant youth and predict worsening of glycemic control Alterations of 2-hydroxybutyrate metabolism predict incipient deterioration of β-cell function and longitudinal worsening of glycemic tolerance. | [63] |
Untargeted | NMR | IR | 170 healthy normal weight children (5, 14 and 16 years) | Serum | IR higher in girls than in boys. In healthy normal weight children IR was associated with reduced concentrations of BCAA, 2-ketobutyrate, citrate and 3-hydroxybutyrate, and higher concentrations of lactate and alanine. | [64] |
Semi-targeted | LC-MS/MS, GC-MS | Obesity | Obese (n = 84) Overweight (n = 28) Normal-weight (n = 150) Median age 7.7 years 50% boys 50% girls | Plasma | OB vs NW: | [53] |
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Semi-targeted | LC-MS/MS, GC-MS | Obesity and IR | Hispanic children Obese (n = 450) Non-obese (n = 353) Boys (n= 405) Girls (n = 398). (4–19 years). Mean age 11.1 years | Plasma | OB vs NOB: | [56] |
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Semi-targeted | LC-MS/MS, GC-MS | Obesity | Longitudinal study for 5 years: Obese (n = 68) Overweight (n = 23) Normal weight (n = 122) 48.8% boys Median age 7.7 years | Plasma | BCAA is not associated with worsening metabolic health during early adolescence. Inverse association of the BCAA pattern with a change in fasting glucose in boys. Direct relation of BCAA pattern with a change in serum triglycerides in girls. Higher score for androgen hormone pattern at baseline corresponds with a decrease in leptin an increase in CRP in girls. | [55] |
Targeted | LC-MS/MS, GC-MS | Obesity and IR | 100 prepubertal obese children. Boys (n = 50, 50% IR and 50% non-IR) Girls (n = 50, 50% IR and 50% non-IR) 5–10 years | Serum | IR vs non-IR: | [62] |
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Targeted | MS/MS | Obesity and T2D | Case-control: Obese (n = 64) Obese with TD2 (n = 17) Normal-weight (n = 39) 12–17 years | Plasma | T2D vs OB/NW: | [87] |
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T2D/OB vs NW: | ||||||
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No differences in fasting FFA levels | ||||||
Targeted | MS/MS | Obesity, IR and T2D | Case-control: Obese (n = 57) Obese prediabetes (n = 27) Obese T2D (n = 17) Normal-weight (n = 38) 13–14 years | Plasma | BCAA and BCAA intermediates correlated: positively with insulin sensitivity and DI | [79] |
Targeted | LC-MS/MS | Obesity and IR | Cross sectional study: 69 healthy children and adolescents 8-18 years Longitudinal cohort study in subset: Subgroup of 17 participants 8-13 years | Plasma | OB vs NW: | [72] |
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Targeted | MS/MS | Obesity and IR | Cross-sectional study: Obese (n = 82) Boys (n = 41) Girls (n = 41) 12–18 years | Plasma | BCAA levels and by products of BCAA catabolism are higher in males than females with similar BMI. In males, HOMA-IR correlated: | [74] |
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In females, HOMA-IR correlated: | ||||||
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Adiponectin correlated inversely with BCAA and uric acid in males, but not females | ||||||
Targeted | LC-MS/MS | Obesity and IR | Identify biomarkers predictive of future disease risk- Obese (n = 46) Obese to normal weight (n = 18) Normal-weight (n = 45) 9–11 years | Plasma | Baseline BCAA concentration as a predictor of future risk of insulin resistance and metabolic syndrome OB vs NW: | [85] |
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Targeted | MS/MS | Obesity and IR | Longitudinal study: 80 obese Caucasian children. 40 participate in one-year lifestyle interventions 8–15 years | Serum | Tyr was the only metabolite significantly associated with HOMA-IR at baseline and after 1-year intervention. No association between HOMA-IR and BCAA. | [84] |
Targeted | MS/MS | Obesity and IR | 430 control (13–15 years). 91 morbid obese (12–16 years) | Plasma | Accumulation of ADMA is associated with modulation of insulin signaling and insulin resistance. ADMA decreased after obesity intervention program | [68] |
Targeted | MS/MS, LC-MS/MS | Obesity and IR | Meta-analysis 1020 pre-pubertal children from three European studies. 8–10 years | Plasma |
| [67] |
Targeted | GC-MS | Obesity and IR | 20 obese with IR 67 obese without IR 8.5–17.9 years | Urine | The steroidal signature IR vs non-IR: | [59] |
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The authors suggest a vicious cycle model, whereby glucocorticoids induce IR. | ||||||
Targeted | MS/MS | Obesity and Metabolic Risk | Non-OW/OB and low MetRisk (n = 335) Non-OW/OB and high MetRisk (n = 29) OW/OB and low MetRisk (n = 58) OW/OB and high MetRisk (n = 102) Girls 48.3% Boys 51.7% 11–16 years | Plasma | Lower levels of LCFA in non-OW/OB with high MetRisk and OW/OB with high MetRisk compared to mon-OW/OB with low MetRisk. Higher levels of BCAA metabolite pattern in OW/OB with high MetRisk compared to non-OW/OB with low MetRisk. Higher levels of DAG in OW/OB with high MetRisk vs non-OB/OW with low MetRisk. Higher score of androgen steroid hormones pattern in OW/OB with high MetRisk compared to Non-OW/OB with low MetRisk. Higher levels of AcylCN in non-OW/OB with high MetRisk compared to non-OW/OB with low MetRisk. Lower levels of AcylCN in OW/OB with high MetRisk compared to Non-OW/OB with low MetRisk. | [76] |
5. Conclusions
Funding
Conflicts of Interest
References
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Rupérez, F.J.; Martos-Moreno, G.Á.; Chamoso-Sánchez, D.; Barbas, C.; Argente, J. Insulin Resistance in Obese Children: What Can Metabolomics and Adipokine Modelling Contribute? Nutrients 2020, 12, 3310. https://doi.org/10.3390/nu12113310
Rupérez FJ, Martos-Moreno GÁ, Chamoso-Sánchez D, Barbas C, Argente J. Insulin Resistance in Obese Children: What Can Metabolomics and Adipokine Modelling Contribute? Nutrients. 2020; 12(11):3310. https://doi.org/10.3390/nu12113310
Chicago/Turabian StyleRupérez, Francisco J., Gabriel Á. Martos-Moreno, David Chamoso-Sánchez, Coral Barbas, and Jesús Argente. 2020. "Insulin Resistance in Obese Children: What Can Metabolomics and Adipokine Modelling Contribute?" Nutrients 12, no. 11: 3310. https://doi.org/10.3390/nu12113310