July 15, 2011 During intrauterine life and lactation, undernutrition brings about modifications involving DNA, leading to metabolic pathologies at the adult age. Researchers from CNRS, INRA and Inserm have demonstrated for the first time, through an animal-based study, such repercussions at the level of the leptin gene, the hormone that regulates satiety and metabolism. Published in The FASEB Journal, this work could, in the longer term, have an impact on the prevention of metabolic diseases, medically assisted procreation and care for premature infants.
Over the last ten years or so, studies carried out on humans have shown that the intrauterine environment and, in particular, maternal nutrition play an important role in the onset of complex diseases such as obesity, diabetes or hypertension at the adult age. Molecular mechanisms of fetal programming, which scientists are attempting to decipher, are behind such observations.
Researchers from the Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière (CRICM, CNRS/UPMC/Inserm) and the Unité de Nutrition Humaine (INRA/Université Clermont 1) specifically studied the consequences of maternal nutrition during the perinatal period (gestation followed by lactation) on epigenetic modifications of the genome. The term epigenetic describes stable alterations of the expression of genes that do not cause any change in the nucleotide sequence of DNA. These alterations involve chemical transformations, such as DNA methylation and/or histone modifications (methylation, acetylation and deacetylation).
Pregnant mice were fed from the first day of gestation up to weaning either with a diet containing 22% protein (control mice), or with a low protein diet containing 10% protein. Then, from weaning, all the baby mice were fed a control diet.
The result was that young mice whose mothers had been given a low protein diet were, as adults, thinner than the control mice and exhibited metabolic disorders. The researchers directly linked these consequences of protein deficiency during the perinatal period to demethylation at the level of the leptin gene. This epigenetic modification is specific, since overall methylation of the genome is not affected. The scientists decided to focus their studies on the leptin gene, because this molecule is crucial to the body's energy balance: it is the hormone that regulates fat reserves.
This work thus reveals the type of molecular process that takes place during the perinatal period and leaves an "imprint" in the genes of the fetus, lasting throughout the individual's lifetime. Understanding such programming mechanisms is essential to define prevention policies for these diseases, which are a major public health issue. This type of study is also useful, both in terms of cell culturing conditions in medically-assisted procreation techniques and nutrition of very premature babies in hospital.
 Researchers from the Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière (CRICM, CNRS/UPMC/Inserm) and the Unité de Nutrition Humaine (INRA/Université Clermont 1).  Methylation is a chemical modification consisting in the addition of a methyl group (CH3) to a substrate, in this particular instance DNA, which may be methylated both at the level of the cytosines and at the level of the histones, the proteins that surround DNA.
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- C Jousse, L Parry, S Lambert-Langlais, AC Maurin, J Averous, A Bruhat, V Carraro, J Tost, P Letteron, P Chen, R Jockers, JM Launay, J Mallet, P Fafournoux. Perinatal Undernutrition Affects the Methylation and Expression of the Leptin Gene in Adults: Implication for the Understanding of Metabolic Syndrome. FASEB Journal, June 13, 2011
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