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

作者: Tomas F Gianotti , Silvia Sookoian , Guillermo Dieuzeide , Silvia I García , Carolina Gemma

DOI: 10.1038/OBY.2008.253

关键词: Mitochondrial DNATFAMGenotypingBiologyPopulationGenotypeMitochondrial biogenesisRestriction fragment length polymorphismGeneticsMolecular biologyInsulin resistanceNutrition and DieteticsMedicine (miscellaneous)Endocrinology, Diabetes and MetabolismEndocrinology

摘要: The aim of this study was to investigate whether mitochondrial DNA (mtDNA) content is associated with insulin resistance (IR) in a sample adolescents features metabolic syndrome. We further studied the link between polymorphisms three genes involved biogenesis and presence deleted mtDNA content. Data blood samples were collected from 175 out cross-sectional, population-based 934 high school students. On basis median value homeostasis model assessment IR (HOMA-IR) whole (2.2), population divided into two groups: noninsulin (NIR) IR. quantification using nuclear (nDNA) as reference carried real-time quantitative PCR method. Genotyping for peroxisome proliferator-activated receptor-γ (PPAR-γ) (pro12Ala), PPAR- γ coactivator-1α (PGC-1α) (Gly482Ser), Tfam (rs1937 rs12247015) performed by PCR-based restriction fragment length polymorphism. Long-extension amplify genome. mtDNA/nDNA ratio significantly lower group (median: 9.08, range: 68.94) comparison NIR (12.24, 71.92) (P < 0.03). Besides, inversely correlated HOMA (R: −0.18, P 0.02), glucose −0.21, 0.008), uric acid Genotypes γ, PGC-1α, variants not ratio. did show significant levels deletions. In conclusion, our findings indicate that reduced peripheral leukocytes This result seems be related previously mentioned regulation biogenesis.

参考文章(33)
David Altshuler, Joel N. Hirschhorn, Mia Klannemark, Cecilia M. Lindgren, Marie-Claude Vohl, James Nemesh, Charles R. Lane, Stephen F. Schaffner, Stacey Bolk, Carl Brewer, Tiinamaija Tuomi, Daniel Gaudet, Thomas J. Hudson, Mark Daly, Leif Groop, Eric S. Lander, The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nature Genetics. ,vol. 26, pp. 76- 80 ,(2000) , 10.1038/79216
Jerry Lee, David Sparrow, Pantel S. Vokonas, Lewis Landsberg, Scott T. Weiss, Uric Acid and Coronary Heart Disease Risk: Evidence for a Role of Uric Acid in the Obesity-Insulin Resistance Syndrome The Normative Aging Study American Journal of Epidemiology. ,vol. 142, pp. 288- 294 ,(1995) , 10.1093/OXFORDJOURNALS.AJE.A117634
Enzo Nisoli, Emilio Clementi, Michele O. Carruba, Salvador Moncada, Defective Mitochondrial Biogenesis: A Hallmark of the High Cardiovascular Risk in the Metabolic Syndrome? Circulation Research. ,vol. 100, pp. 795- 806 ,(2007) , 10.1161/01.RES.0000259591.97107.6C
Zhidan Wu, Pere Puigserver, Ulf Andersson, Chenyu Zhang, Guillaume Adelmant, Vamsi Mootha, Amy Troy, Saverio Cinti, Bradford Lowell, Richard C. Scarpulla, Bruce M. Spiegelman, Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC-1 Cell. ,vol. 98, pp. 115- 124 ,(1999) , 10.1016/S0092-8674(00)80611-X
HONG KYU LEE, KYONG SOO PARK, YOUNG MIN CHO, YUN YONG LEE, YOUNGMI KIM PAK, Mitochondria‐Based Model for Fetal Origin of Adult Disease and Insulin Resistance Annals of the New York Academy of Sciences. ,vol. 1042, pp. 1- 18 ,(2005) , 10.1196/ANNALS.1338.001
J. Ek, G. Andersen, S. A. Urhammer, P. H. Gæde, T. Drivsholm, K. Borch-Johnsen, T. Hansen, O. Pedersen, Mutation analysis of peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to Type II diabetes mellitus Diabetologia. ,vol. 44, pp. 2220- 2226 ,(2001) , 10.1007/S001250100032
Langping He, Patrick F Chinnery, Steve E Durham, Emma L Blakely, Theresa M Wardell, Gillian M Borthwick, Robert W Taylor, Douglass M Turnbull, Detection and quantification of mitochondrial DNA deletions in individual cells by real-time PCR Nucleic Acids Research. ,vol. 30, ,(2002) , 10.1093/NAR/GNF067
K. Hara, K. Tobe, T. Okada, H. Kadowaki, Y. Akanuma, C. Ito, S. Kimura, T. Kadowaki, A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes. Diabetologia. ,vol. 45, pp. 740- 743 ,(2002) , 10.1007/S00125-002-0803-Z
Patricia Inés Porto, Silvia Inés García, Guillermo Dieuzeide, Claudio González, María Silvina Landa, Carlos José Pirola, Clinical features of the metabolic syndrome in adolescents: minor role of the Trp64Arg beta3-adrenergic receptor gene variant. Pediatric Research. ,vol. 55, pp. 836- 841 ,(2004) , 10.1203/01.PDR.0000119367.21770.D7