Acute and long-term nutrient-led modifications of gene expression: potential role of SIRT1 as a central co-ordinator of short and longer-term programming of tissue function.
Environmental factors can influence the acute and longer-term risks of developing diseases, including type 2 diabetes mellitus and cardiovascular disease; however, the underlying mechanism remains elusive. Increasing evidence suggests that these effects can be achieved by modification of metabolic gene expression. These include acute changes in histone methylation, acetylation, phosphorylation, and ubiquitination and longer-term DNA silencing elicited by DNA methylation. Thus, an increased risk of disease may reflect acute or chronic stable modification of genes that regulate nutrient handling, leading to altered nutrient utilization (increased lipid oxidation at the expense of glucose utilization) and/or changes in the balance between nutrient storage and energy production, thereby favoring the development of obesity. The review addresses the hypothesis that early-life epigenetic programming of gene expression could be mirrored by changes in acute function of nuclear receptors, in particular the peroxisome proliferator-activated receptors, achieved by enzymes that are more conventionally involved in regulating DNA methylation and post-transcriptional modification of histones. Emphasis is placed on the potential importance of the protein deacetylase sirtuin-1 as a central co-ordinator.
Holness
Mark J
MJ
Queen Mary University of London, Centre for Diabetes, Blizard Institute of Cell and Molecular Science, Bart's and the London, London, United Kingdom. m.j.holness@qmul.ac.uk
Caton
Paul W
PW
Sugden
Mary C
MC
D000273:Adipose Tissue; D000818:Animals; D002318:Cardiovascular Diseases; D003924:Diabetes Mellitus, Type 2; D047108:Embryonic Development / Q000235:genetics; D004777:Environment; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D006304:Health Status; D006801:Humans; D007333:Insulin Resistance; D008019:Life Style; D008429:Maternal Welfare; D009747:Nutritional Physiological Phenomena / Q000235:genetics; D009765:Obesity; D047495:PPAR gamma / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics; D056564:Sirtuin 1 / Q000502:physiology*
D047495:PPAR gamma; C447939:SIRT1 protein, human; D056564:Sirtuin 1