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The early programming of metabolic health: is epigenetic setting the missing link?
MedLine Citation:
PMID:  21543542     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Adult health is dependent, in part, on maternal nutrition and growth during early life, which may independently affect insulin sensitivity, body composition, and overall energy homeostasis. Since the publication of the "thrifty phenotype hypothesis" by Hales and Barker (Diabetologia 1992;35:595-601), animal experiments have focused on establishing the mechanisms involved, which include changes in fetal cortisol, insulin, and leptin secretion or sensitivity. Intrauterine growth retardation can be induced by either prolonged modest changes in maternal diet or by more severe changes in uterine blood supply near to term. These contrasting challenges result in different amounts of cellular stress in the offspring. In addition, shifts in the transcriptional activity of DNA may produce sustained metabolic adaptations. Within tissues and organs that control metabolic homeostasis (eg, hypothalamus, adipose tissue, stomach, skeletal muscle, and heart), a range of phenotypes can be induced by sustained changes in maternal diet via modulation of genes that control DNA methylation and by histone acetylation, which suggests epigenetic programming. We now need to understand how changes in maternal diet affect DNA and how they are conserved on exposure to oxidative stress. A main challenge will be to establish how the dietary environment interacts with the programmed phenotype to trigger the development of metabolic disease. This may aid in the establishment of nutrigenomic strategies to prevent the metabolic syndrome.
Authors:
Sylvain Sebert; Don Sharkey; Helen Budge; Michael E Symonds
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-4
Journal Detail:
Title:  The American journal of clinical nutrition     Volume:  -     ISSN:  1938-3207     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376027     Medline TA:  Am J Clin Nutr     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Early Life Nutrition Research Unit, Academic Division of Child Health, and Nottingham Respiratory Medicine Biomedical Research Unit, School of Clinical Sciences, University Hospital Nottingham, Nottingham, United Kingdom.
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