Foetal programming by methyl donor deficiency produces steato-hepatitis in rats exposed to high fat diet

Citations Over TimeTop 10% of 2016 papers

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.

Related Papers

• → Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease(2008)250 cited
• → Review article: is non‐alcoholic fatty liver disease a spectrum, or are steatosis and non‐alcoholic steatohepatitis distinct conditions?(2012)215 cited
• → Are Steatosis and Steatohepatitis Triggers of Hepatic Fibrogenesis(2013)2 cited
• → Faculty Opinions recommendation of Combination of N-acetylcysteine and metformin improves histological steatosis and fibrosis in patients with non-alcoholic steatohepatitis.(2008)
• → STUDY OF CELL MODELS OF HEPG2 STEATOSIS AND STEATOHEPATITIS VIABILITY(2023)