Mitochondrial function and insulin resistance in overweight and normal-weight children.
BACKGROUND
Obesity has become an epidemic in children, associated with an increase in insulin resistance and metabolic dysfunction. Mitochondrial function is known to be an important determinant of glucose metabolism in adults. However, little is known about the relationship between mitochondrial function and obesity, insulin resistance, energy expenditure, and pubertal development in children.


METHODS
Seventy-four participants, 37 overweight (> or = 85th percentile body mass index for age and sex) and 37 normal-weight (< 85th percentile) without personal or family history of diabetes mellitus were enrolled. Subjects were evaluated with an oral glucose tolerance test, metabolic markers, resting energy expenditure, Tanner staging, and (31)P magnetic resonance spectroscopy of skeletal muscle for mitochondrial function.


RESULTS
Overweight and normal-weight children showed no difference in muscle ATP synthesis [phosphocreatine (PCr) recovery after exercise] (32.4 +/- 2.3 vs. 34.1 +/- 2.1, P = 0.58). However, insulin-resistant children had significantly prolonged PCr recovery when compared with insulin-sensitive children, by homeostasis model assessment for insulin resistance quartile (ANOVA, P = 0.04). Similarly, insulin-resistant overweight children had PCr recovery that was prolonged compared with insulin-sensitive overweight children (P = 0.01). PCr recovery was negatively correlated with resting energy expenditure in multivariate modeling (P = 0.03). Mitochondrial function worsened during mid-puberty in association with insulin resistance.


CONCLUSIONS
Reduced skeletal muscle mitochondrial oxidative phosphorylation, assessed by PCr recovery, is associated with insulin resistance and an altered metabolic phenotype in children. Normal mitochondrial function may be associated with a healthier metabolic phenotype in overweight children. Further studies are needed to investigate the long-term physiological consequences and potential treatment strategies targeting children with reduced mitochondrial function.
Fleischman
Amy
A
Program in Nutritional Metabolism, Massachusetts General Hospital, 55 Fruit Street, LON 207, Boston, Massachusetts 02114, USA. afleischman@partners.org.
Kron
Matthew
M
Systrom
David M
DM
Hrovat
Mirko
M
Grinspoon
Steven K
SK
D000293:Adolescent; D001835:Body Weight / Q000502:physiology*; D002153:Calorimetry, Indirect; D002648:Child; D050171:Dyslipidemias / Q000097:blood / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005247:Feeding Behavior; D005260:Female; D038321:Glycemic Index; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D050177:Overweight / Q000378:metabolism*; D010641:Phenotype; D010725:Phosphocreatine / Q000378:metabolism; D011627:Puberty / Q000502:physiology; D011795:Surveys and Questionnaires
D007328:Insulin; D008055:Lipids; D010725:Phosphocreatine