Dysregulation of sirtuins and key metabolic genes in skeletal muscle of pigs with intrauterine growth restriction is associated to alterations of circulating IGF-1 - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2015

Dysregulation of sirtuins and key metabolic genes in skeletal muscle of pigs with intrauterine growth restriction is associated to alterations of circulating IGF-1

Résumé

[b]Background and aims[/b]: [br/]Prenatal and early postnatal lives are important determinants of future health, and intrauterine growth restriction (IUGR) - associated low birth weight predisposes to the development of metabolic and cardiovascular disease in adult life, but the mechanisms are largely unknown.We hypothesize here that IUGR might confer gene expression alterations, predisposing to metabolic disease.[br/][b]Materials and methods[/b]:[br/]Using a porcine model of spontaneous IUGR, we determined in utero (71, 112 days post-conception) and earlypostnatal (2 days post-birth) IGF-1, insulin and leptin levels, and in parallel we investigated skeletalmuscle (Longissimus dorsi) gene expression of sirtuins and key metabolic genes (IRS1, GLUT4, HK2 and GAPDH).[br/][b]Results[/b]: In IUGR, we observed impaired IGF-1, insulin and leptin serum levels. Gene expression of sirtuin 1, 5, 6, 7, GLUT4 and HK2 exhibited significant correlations with gestational age or fetus/newborn body weight. SIRT1 and HK2 expression displayed an age- and weight dependent downregulation in controls, which was lost in IUGR pigs. Conversely, SIRT2 and GLUT4 were upregulated in IUGR pigs. Within the set of genes studied, we found a significant correlation between IGF-1 levels and gene expression, indicating that IGF-1 is limiting in IUGR.IUGR-dependent gene alterations were partly linked to epigenetic changes on histone H3 acetylation and methylation. [br/][b]Conclusion[/b]: [br/]Our observations indicate that several sirtuins andmetabolic genes display specific gene expression trajectories during fetal and early postnatal life, which are altered in IUGR, and are related to hormonal dysregulations observed in IUGR. Given the importance of these genes in metabolic control, their perinatal alterations might contribute to the predisposition to metabolic disease and diabetes in adulthood.
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Dates et versions

hal-01205625 , version 1 (19-11-2015)

Identifiants

  • HAL Id : hal-01205625 , version 1
  • PRODINRA : 325805
  • WOS : 000359820901395

Citer

Luciano Pirola, Sabrina Chriett, Isabelle Luron, Hubert Vidal. Dysregulation of sirtuins and key metabolic genes in skeletal muscle of pigs with intrauterine growth restriction is associated to alterations of circulating IGF-1. 51st Annual Meeting of the European Association for the Study of Diabetes (EASD), 2015, NA, France. Springer Link, Diabetologia, 58 (Suppl. 1), 2015, Diabetologia. ⟨hal-01205625⟩
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