Programming by Methyl Donor Deficiency during Pregnancy and Lactation Produces Cardiomyopathy in Adult Rats Subjected to High Fat Diet. Issue 13 (28th May 2021)

• Record Type: Journal Article
• Authors: Li, Zhen; Kosgei, Viola J.; Bison, Anais; Alberto, Jean‐Marc; Umoret, Remi; Maskali, Fatiha; Brunaud, Laurent; Guéant, Jean‐Louis; Guéant‐Rodriguez, Rosa‐Maria
• Is Part Of: Molecular nutrition & food research. Volume 65:Issue 13(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-05-28
• Subjects: fetal programing -- folate -- myocardiopathy -- one carbon metabolism -- vitamin B12; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.202100065
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : Scope: Vitamin B12 and folate (methyl donors) deficiency is frequent during pregnancy. Experimental rat models with methyl donor deficit during pregnancy and lactation (Initial methyl donor deficit (iMDD)) produce impaired myocardium fatty acid oxidation and mitochondrial energy metabolism at weaning. Methods and Results: The consequences of iMDD on heart of rat pups under normal diet after weaning and high fat diet (HF) between day (D) 50 and D185 are investigated. iMDD/HF induces increased histological fibrosis and increased B‐type natriuretic peptide blood level. Inflammation is evidenced by increased protein expression of NFkB, Caspase1, and IL1β and fibrosis by increased expression of αSMA, col1a1, and col1a2 in females, but not in males. Fibrosis is related to increased angiotensin at D50 and D185 and increased protein expression of TGFB1 and AT1 angiotensin receptors at D185. The limited fibrosis in males is consistent with increased expression of AT2, the antagonist receptor of AT1. The increased expression of GLUT4 and decreased expression of PGC1α and PPARα reflect a shift from fatty acid oxidation to glycolysis. Conclusion: Developmental programming by iMDD produces cardiomyopathy in female offspring exposed to HF. The cardiomyopathy is linked to inflammation and fibrosis through angiotensin‐AT2 and TGFB1 pathways and alteration of energy metabolism. Abstract : A fetal programming of methyl donor deficiency during gestation and lactation (iMDD) is shown previously, with low birth weight and cardiac hypertrophy in rat offspring; it produced cardiomyopathy in day‐185 female offspring exposed to high‐fat diet since day‐50, with inflammation and fibrosis through angiotensin and TGFB1 pathways. The limited fibrosis in males is related to increased expression of angiotensin receptor AT2.