A Decreased Mitochondrial DNA Content Is Related to Insulin Resistance in Adolescents.

FERNANDEZ GIANOTTI T; SOOKOIAN S; DIEUZEIDE G; GARCIA SI; GEMMA C; GONZALEZ CD; PIROLA CJ

Obesity (Silver Spring, ex Obesity Research)

Nature Publishing Group.

Lugar: London, United Kindom.; Año: 2008 vol. 16 p. 1591 - 1595

1930-7381

Objective: to investigate whether mitochondrial DNA (mtDNA) content is associated with insulin resistance in a sample of adolescents with features of metabolic syndrome. We further studied the link between polymorphisms in 3 genes involved in mitochondrial biogenesis as well as the presence of deleted and mtDNA content. Subjects: Data and blood samples were collected from 175 adolescents out of a cross-sectional, population-based study of 934 high school students. Based on the median value of HOMA-IR of the whole sample (2.2), the population was divided into 2 groups: non-insulin resistance (NIR) and insulin resistance (IR). Methods: mtDNA quantification using nuclear DNA (nDNA) as a reference was carried out by a real-time quantitative PCR method. Genotyping for PPAR-g (pro12Ala), PGC-1a (Gly482Ser) and Tfam (rs1937 and rs12247015) polymorphisms was assessed by PCR-RFLP. Long-extension PCR was performed to amplify the whole mitochondrial genome. Results: 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-g, PGC-1a and Tfam variants were not associated with the mtDNA/nDNA ratio. Long-extension PCR did not show significant levels of mtDNA deletions. Conclusion: Our findings indicate that reduced mtDNA content in peripheral leukocytes is associated with insulin resistance. This result seems not to be related with the previously mentioned variants in genes involved in the regulation of mitochondrial biogenesis.