Maternal western diet primes non‐alcoholic fatty liver disease in adult offspring in mice (1085.4)

Abstract

Metabolic programming via the maternal diet during gestation may play a role in the development of different aspects of the metabolic syndrome. Using a mouse model we aimed to characterise the role of maternal western type diet in the development of non‐alcoholic fatty liver disease (NAFLD) in the offspring. Female mice were fed either a western (W) or low‐fat control (L) semi‐synthetic diet before and during gestation and lactation. At weaning, male offspring were assigned either the W or the L diet, generating four experimental groups: WW, WL, LW and LL offspring. Biochemical, histological and epigenetic indicators were investigated at 29 weeks of age. Male offspring exposed to prenatal and post‐weaning western‐style diet (WW) showed hepatomegaly combined with accumulation of hepatic cholesterol and triglycerides. This was associated with up‐regulation of de novo lipid synthesis, inflammation and dysregulation of lipid storage. Histopathological analysis revealed the presence of advanced steatohepatitis in WW offspring. In addition, alterations in DNA methylation in key metabolic genes (Ppara, Insig, and Fasn) were detected. In conclusion, maternal dietary fat intake during early development programs susceptibility to liver disease in male offspring, mediated by disturbances in lipid metabolism and inflammatory response. Long lasting epigenetic changes may underlie this dysregulation.Grant Funding Source: Supported by CTMM and NHS