title: Foetal programming by methyl donor deficiency produces steato-hepatitis in rats exposed to high fat diet.
abstract: Non-alcoholic steatohepatitis (NASH) is a manifestation of metabolic syndrome, which emerges as a major public health problem. Deficiency in methyl donors (folate and vitamin B12) during gestation and lactation is frequent in humans and produces foetal programming effects of metabolic syndrome, with small birth weight and liver steatosis at day 21 (d21), in rat pups. We investigated the effects of fetal programming on liver of rats born from deficient mothers (iMDD) and subsequently subjected to normal diet after d21 and high fat diet (HF) after d50. We observed increased abdominal fat, ASAT/ALAT ratio and angiotensin blood level, but no histological liver abnormality in d50 iMDD rats. In contrast, d185 iMDD/HF animals had hallmarks of steato-hepatitis, with increased markers of inflammation and fibrosis (caspase1, cleaved IL-1β, α1(I) and α2(I) collagens and α-SMA), insulin resistance (HOMA-IR and Glut 2) and expression of genes involved in stellate cell stimulation and remodelling and key genes triggering NASH pathomechanisms (transforming growth factor beta super family, angiotensin and angiotensin receptor type 1). Our data showed a foetal programming effect of MDD on liver inflammation and fibrosis, which suggests investigating whether MDD during pregnancy is a risk factor of NASH in populations subsequently exposed to HF diet.
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Bison
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Marchal-Bressenot
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Ilef
authors.initials: I
authors.lastname: Elamouri
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Feigerlova
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Lu
authors.initials: L
authors.lastname: Peng
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Remi
authors.initials: R
authors.lastname: Houlgatte
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Beck
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Gregory
authors.initials: G
authors.lastname: Pourié
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Alberto
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Remy
authors.initials: R
authors.lastname: Umoret
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Conroy
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guéant
authors.affiliation: Inserm U954, Nutrition-Genetics-Environmental Risk Exposure (N-GERE), University of Lorraine, BP 184, 54511, Vandœuvre-lès-Nancy, France.
authors.forename: Rosa-Maria
authors.initials: RM
authors.lastname: Guéant-Rodriguez
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005333:Fetus / Q000196:embryology / Q000473:pathology; D018811:Maternal Exposure / Q000009:adverse effects*; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051381:Rats
chemical_list: D004041:Dietary Fats