A decreased mitochondrial DNA content is related to insulin resistance in adolescents.
The aim of this study was to investigate whether mitochondrial DNA (mtDNA) content is associated with insulin resistance (IR) in a sample of adolescents with features of metabolic syndrome. We further studied the link between polymorphisms in three genes involved in mitochondrial biogenesis and the presence of deleted mtDNA and mtDNA content. Data and blood samples were collected from 175 adolescents out of a cross-sectional, population-based study of 934 high school students. On the basis of the median value of homeostasis model assessment of IR (HOMA-IR) of the whole sample (2.2), the population was divided into two groups: noninsulin resistance (NIR) and IR. mtDNA quantification using nuclear DNA (nDNA) as a reference was carried out using a real-time quantitative PCR method. Genotyping for peroxisome proliferator-activated receptor-gamma (PPAR-gamma) (pro12Ala), PPAR- gamma coactivator-1alpha (PGC-1alpha) (Gly482Ser), and Tfam (rs1937 and rs12247015) polymorphisms was performed by PCR-based restriction fragment length polymorphism. Long-extension PCR was performed to amplify the whole mitochondrial genome. The mtDNA/nDNA ratio was significantly lower in the IR group (median: 9.08, range: 68.94) in comparison with the NIR group (12.24, 71.92) (P<0.03). Besides, the mtDNA/nDNA ratio was inversely correlated with HOMA (R: -0.18, P<0.02), glucose (R: -0.21, P<0.008), and uric acid (R: -0.18, P<0.03). Genotypes for the PPAR- gamma, PGC-1alpha, and Tfam variants were not associated with the mtDNA/nDNA ratio. Long-extension PCR did not show significant levels of mtDNA deletions. In conclusion, our findings indicate that reduced mtDNA content in peripheral leukocytes is associated with IR. This result seems not to be related with the previously mentioned variants in genes involved in the regulation of mitochondrial biogenesis.
Gianotti
Tomas F
TF
Molecular Genetics and Biology of Complex Diseases Department, Institute of Medical Research A. Lanari, University of Buenos Aires-CONICET, Ciudad Autónoma de Buenos Aires, Argentina.
Sookoian
Silvia
S
Dieuzeide
Guillermo
G
García
Silvia I
SI
Gemma
Carolina
C
González
Claudio D
CD
Pirola
Carlos J
CJ
D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D004272:DNA, Mitochondrial / Q000097:blood*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D024101:Mitochondrial Proteins / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011159:Population Surveillance; D011795:Surveys and Questionnaires; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014527:Uric Acid / Q000097:blood
D001786:Blood Glucose; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D007328:Insulin; D008055:Lipids; D024101:Mitochondrial Proteins; D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C499631:TFAM protein, human; D014157:Transcription Factors; D014527:Uric Acid