title: Perinatal undernutrition affects the methylation and expression of the leptin gene in adults: implication for the understanding of metabolic syndrome.
abstract: Transient environmental influences, such as perinatal nutritional stress, may induce deleterious metabolic symptoms that last for the entire life of individuals, implying that epigenetic modifications play an important role in this process. We have investigated, in mice, the consequences of maternal undernutrition during gestation and lactation on DNA methylation and expression of the leptin gene, which plays a major regulatory role in coordinating nutritional state with many aspects of mammalian biology. We show that animals born to mothers fed a low-protein-diet (F1-LPD group) have a lower body weight/adiposity and exhibit a higher food intake than animals born to mothers fed a control diet (F1-CD group). These modifications persisted throughout life and were associated with lower levels of leptin mRNA and protein in starved F1-LPD mice, emphasizing that maternal protein-undernutrition affects the balance between food intake and energy expenditure in adults. Moreover, this nutritional stress resulted in the removal of methyls at CpGs located in the promoter of leptin, causing a permanent specific modification in the dynamics of the expression of leptin, which exhibits a stronger induction in the F1-LPD than in F1-CD mice in response to a meal. This study is an example of a molecular rationale linking transient environmental influences to permanent phenotypic consequences.
authors.affiliation: Institut National de Recherche Agronomique (INRA), Unité Mixte de Recherche (UMR) 1019 Nutrition Humaine, F-63122 St. Genès Champanelle, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Jousse
authors.forename: Laurent
authors.initials: L
authors.lastname: Parry
authors.forename: Sarah
authors.initials: S
authors.lastname: Lambert-Langlais
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Maurin
authors.forename: Julien
authors.initials: J
authors.lastname: Averous
authors.forename: Alain
authors.initials: A
authors.lastname: Bruhat
authors.forename: Valérie
authors.initials: V
authors.lastname: Carraro
authors.forename: Jorg
authors.initials: J
authors.lastname: Tost
authors.forename: Philippe
authors.initials: P
authors.lastname: Letteron
authors.forename: Patty
authors.initials: P
authors.lastname: Chen
authors.forename: Ralf
authors.initials: R
authors.lastname: Jockers
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Launay
authors.forename: Jacques
authors.initials: J
authors.lastname: Mallet
authors.forename: Pierre
authors.initials: P
authors.lastname: Fafournoux
mesh_terms: D000818:Animals; D001483:Base Sequence; D001823:Body Composition; D018899:CpG Islands; D004032:Diet; D004044:Dietary Proteins / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000209:etiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D004044:Dietary Proteins; D020738:Leptin; D012333:RNA, Messenger