Mitochondrial DNA content and function, childhood obesity, and insulin resistance
Zohreh Shoar1, Michael J Goldenthal2, Francesco De Luca1
1a Section of Endocrinology and Diabetes and.
Insights
Mitochondrial DNA content correlates with childhood obesity but not metabolic syndrome markers. Further research is needed to understand the link between mitochondrial function, body fat, and insulin resistance.
Area of Science:
- Pediatric Endocrinology
- Mitochondrial Biology
- Metabolic Health
Background:
- Childhood obesity is a growing concern with potential links to metabolic dysfunction.
- Mitochondrial dysfunction has been implicated in metabolic diseases.
- Understanding the role of mitochondria in pediatric obesity is crucial.
Purpose of the Study:
- To compare mitochondrial enzyme activity in obese versus non-obese children.
- To investigate the association between mitochondrial DNA content, function, and metabolic syndrome markers in obese children.
Main Methods:
- Collected anthropometric and clinical data from 140 children (2-18 years).
- Assessed mitochondrial respiratory enzyme activity (Complex I, IV, Citrate Synthase) from buccal swabs.
- Quantitated serum metabolic parameters and mitochondrial DNA (mt/nDNA ratio) in mononuclear cells of obese children.
Main Results:
- No significant differences in respiratory complex enzyme activity between obese and normal-weight children.
- In obese children, the mitochondrial to nuclear DNA (mt/nDNA) ratio positively correlated with BMI Z-score and percentile.
- Complex IV activity showed a positive association with fasting insulin levels, explaining 45% of its variation.
Conclusions:
- Mitochondrial DNA content is directly related to childhood obesity.
- Mitochondrial DNA content is not associated with metabolic syndrome markers or insulin resistance in children.
- Larger longitudinal studies are required to clarify the relationship between mitochondrial function, adiposity, and insulin resistance.
Objectives:
The objectives of our study were to compare the mitochondrial enzyme activity between obese and non-obese children and to assess the association between mitochondrial DNA content and function and markers of metabolic syndrome.
Methods:
Clinical and anthropometric data of obese and normal-weight children ages 2-18 years were collected. We collected buccal swabs for mitochondrial respiratory enzymes (complex I, IV, and Citrate Synthase). In obese children only, serum levels of metabolic parameters and mitochondrial DNA from mononuclear cells were quantitated.
Results:
We recruited 75 obese and 65 normal-weight children. There was no difference in respiratory complex enzyme activity levels between obese and normal-weight subjects. In obese subjects, mitochondrial to nuclear DNA (mt/nDNA) ratio was significantly correlated with BMI Z-score and BMI percentile (p < 0.05, and p < 0.01, respectively), and the strength of this correlation was proportionate to the degree of obesity. We did not find any association between mt/nDNA ratio and metabolic parameters. We observed a significant positive association between complex IV activity and fasting insulin level (p < 0.05). Finally, fasting insulin explained 45% of the variation in the complex IV activity level (p < 0.05).
Conclusion:
Our findings indicate that mitochondrial DNA content is directly related to obesity, but not to the markers of metabolic syndrome/insulin resistance in children. Longitudinal studies involving larger samples are needed to confirm our findings and help elucidate the relationship between mitochondrial function, adiposity, and insulin resistance.
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