Epigenetics of programmed obesity: alteration in IUGR rat hepatic IGF1 mRNA expression and histone structure in rapid vs. delayed postnatal catch-up growth. Am J Physiol Gastrointest Liver Physiol 2010 Nov;299(5):G1023-9
Date
09/04/2010Pubmed ID
20813916Pubmed Central ID
PMC2993166DOI
10.1152/ajpgi.00052.2010Scopus ID
2-s2.0-78149482533 (requires institutional sign-in at Scopus site) 122 CitationsAbstract
Maternal food restriction (FR) during pregnancy results in intrauterine growth-restricted (IUGR) offspring that show rapid catch-up growth and develop metabolic syndrome and adult obesity. However, continued nutrient restriction during nursing delays catch-up growth and prevents development of obesity. Epigenetic regulation of IGF1, which modulates growth and is synthesized and secreted by the liver, may play a role in the development of these morbidities. Control (AdLib) pregnant rats received ad libitum food through gestation and lactation, and FR dams were exposed to 50% food restriction from days 10 to 21. FR pups were nursed by either ad libitum-fed control dams (FR/AdLib) or FR dams (FR/FR). All pups were weaned to ad libitum feed. Maternal FR resulted in IUGR newborns with significantly lower liver weight and, with the use of chromatin immunoprecipitation, decreased dimethylation at H3K4 in the IGF1 region was observed. Obese adult FR/AdLib males had decreased dimethylation and increased trimethylation of H3K4 in the IGF1 region. This corresponded to an increase in mRNA expression of IGF1-A (134 ± 5%), IGF1-B (165 ± 6%), IGF1 exon 1 (149 ± 6%), and IGF1 exon 2 (146 ± 7%) in the FR/AdLib compared with the AdLib/AdLib control group. In contrast, nonobese FR/FR had significantly higher IGF1-B mRNA levels (147 ± 19%) than controls with no difference in IGF1-A, exon 1 or exon 2. Modulation of the rate of IUGR newborn catch-up growth may thus protect against IGF1 epigenetic modifications and, consequently, obesity and associated metabolic abnormalities.
Author List
Tosh DN, Fu Q, Callaway CW, McKnight RA, McMillen IC, Ross MG, Lane RH, Desai MMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
Blotting, Western
Body Weight
Chromatin Immunoprecipitation
Epigenesis, Genetic
Female
Fetal Growth Retardation
Histones
Insulin-Like Growth Factor I
Liver
Maternal Nutritional Physiological Phenomena
Pregnancy
Prenatal Exposure Delayed Effects
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Weaning
