Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
M G M
MG
Pruis
A
A
Lendvai
V W
VW
Bloks
M V
MV
Zwier
J F W
JF
Baller
A
A
de Bruin
A K
AK
Groen
T
T
Plösch
D000375:Aging / Q000378:metabolism*; D000818:Animals; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D048070:Fetal Nutrition Disorders / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*
D004041:Dietary Fats
developmental programming; epigenetics; inflammation