Epigenetic programming at the Mogat1 locus may link neonatal overnutrition with long-term hepatic steatosis and insulin resistance
Por:
Ramon-Krauel M, Pentinat T, Bloks VW, Cebrià-Romero J, Ribó-Gené S, Pérez-Wienese R, Vilà M, Palacios-Marin I, Fernández-Pérez A, Vallejo M, Téllez N, Rodríguez MÀ, Yanes O, Lerin C, Díaz R, Plosch T, Tietge UJF and Jimenez-Chillaron JC
Publicada:
1 nov 2018
Ahead of Print:
29 may 2018
Resumen:
Postnatal overfeeding increases the risk of chronic diseases later in life, including obesity, insulin resistance, hepatic steatosis, and type 2 diabetes. Epigenetic mechanisms might underlie the long-lasting effects associated with early nutrition. Here we aimed to explore the molecular pathways involved in early development of insulin resistance and hepatic steatosis, and we examined the potential contribution of DNA methylation and histone modifications to long-term programming of metabolic disease. We used a well-characterized mouse model of neonatal overfeeding and early adiposity by litter size reduction. Neonatal overfeeding led to hepatic insulin resistance very early in life that persisted throughout adulthood despite normalizing food intake. Up-regulation of monoacylglycerol O-acyltransferase (Mogat)1 conceivably mediates hepatic steatosis and insulin resistance through increasing intracellular diacylglycerol content. Early and sustained deregulation of Mogat1 was associated with a combination of histone modifications that might favor Mogat1 expression. In sum, postnatal overfeeding causes extremely rapid derangements of hepatic insulin sensitivity that remain relatively stable until adulthood. Epigenetic mechanisms, particularly histone modifications, could contribute to such long-lasting effects. Our data suggest that targeting hepatic monoacylglycerol acyltransferase activity during early life might provide a novel strategy to improve hepatic insulin sensitivity and prevent late-onset insulin resistance and fatty liver disease.Ramon-Krauel, M., Pentinat, T., Bloks, V. W., Cebria, J., Ribo, S., Perez-Wienese, R., Vila, M., Palacios-Marin, I., Fernandez-Perez, A., Vallejo, M., Tellez, N., Rodriguez, M. ., Yanes, O., Lerin, C., Diaz, R., Plosch, T., Tietge, U. J. F., Jimenez-Chillaron, J. C. Epigenetic programming at the Mogat1 locus may link neonatal overnutrition with long-term hepatic steatosis and insulin resistance.
Filiaciones:
Ramon-Krauel M:
Endocrinology Department, Institut de Recerca Sant Joan de Déu, Esplugues, Barcelona, Spain
Pentinat T:
Endocrinology Department, Institut de Recerca Sant Joan de Déu, Esplugues, Barcelona, Spain
Bloks VW:
Department of Pediatrics, Section of Molecular Metabolism and Nutrition, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Cebrià-Romero J:
Endocrinology Department, Institut de Recerca Sant Joan de Déu, Esplugues, Barcelona, Spain
Ribó-Gené S:
Endocrinology Department, Institut de Recerca Sant Joan de Déu, Esplugues, Barcelona, Spain
Pérez-Wienese R:
Endocrinology Department, Institut de Recerca Sant Joan de Déu, Esplugues, Barcelona, Spain
Vilà M:
Endocrinology Department, Institut de Recerca Sant Joan de Déu, Esplugues, Barcelona, Spain
Palacios-Marin I:
Endocrinology Department, Institut de Recerca Sant Joan de Déu, Esplugues, Barcelona, Spain
Fernández-Pérez A:
Ciber de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid (CSIC/UAM), Madrid, Spain
Vallejo M:
Ciber de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid (CSIC/UAM), Madrid, Spain
Téllez N:
Ciber de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet, Barcelona, Spain
Rodríguez MÀ:
Ciber de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
Department of Electronic Engineering, Universitat Rovira i Virgili, Tarragona, Spain
Yanes O:
Ciber de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
Department of Electronic Engineering, Universitat Rovira i Virgili, Tarragona, Spain
Lerin C:
Endocrinology Department, Institut de Recerca Sant Joan de Déu, Esplugues, Barcelona, Spain
Díaz R:
Endocrinology Department, Institut de Recerca Sant Joan de Déu, Esplugues, Barcelona, Spain
Plosch T:
Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Tietge UJF:
Department of Pediatrics, Section of Molecular Metabolism and Nutrition, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Jimenez-Chillaron JC:
Endocrinology Department, Institut de Recerca Sant Joan de Déu, Esplugues, Barcelona, Spain
Open Access
|