These authors contributed equally to this work.
Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring
Version of Record online: 13 DEC 2013
© 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd
Special Issue: Metabolic Programming
Volume 210, Issue 1, pages 215–227, January 2014
How to Cite
Pruis, M. G. M., Lendvai, Á., Bloks, V. W., Zwier, M. V., Baller, J. F. W., de Bruin, A., Groen, A. K. and Plösch, T. (2014), Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring. Acta Physiologica, 210: 215–227. doi: 10.1111/apha.12197
- Issue online: 13 DEC 2013
- Version of Record online: 13 DEC 2013
- Accepted manuscript online: 14 NOV 2013 01:09AM EST
- Manuscript Accepted: 10 NOV 2013
- Manuscript Revised: 18 OCT 2013
- Manuscript Revised: 8 OCT 2013
- Manuscript Received: 20 AUG 2013
- Center for Translational Molecular Medicine. Grant Number: 01C-104
- Dutch Heart Foundation
- Dutch Diabetes Research Foundation
- Dutch Kidney Foundation
- developmental programming;
Metabolic programming via components of 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 characterize 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) semisynthetic 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 accumulation was associated with up-regulation of de novo lipid synthesis, inflammation and dysregulation of lipid storage. Elevated hepatic transaminases and increased expression of Tnfa, Cd11, Mcp1 and Tgfb underpin the severity of liver injury. 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.
Maternal dietary fat intake during early development programmes susceptibility to liver disease in male offspring, mediated by disturbances in lipid metabolism and inflammatory response. Long-lasting epigenetic changes may underlie this dysregulation.