| dc.description.abstract | Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and is the
hepatic manifestation of the metabolic syndrome. Obesity is closely associated with NAFLD. The concept
of fetal programming, known through Barker’s hypothesis and the Developmental Origins of Health and
Disease (DOHaD) approach, suggests that early life environment has consequences for adult health. The
contribution of maternal and early life influences on development of NAFLD is less understood, and would
be of importance to be able to point to intervention measures to improve public health. The main objective
of this master thesis was to assess which NAFLD-related signaling pathways are affected after exposure to
a HFD during five different life stages in liver of adult mice. The animal material used in this thesis
originated from a mouse obesity study conducted at the Norwegian Institute of Public Health in 2014. The
mice were divided in five HFD exposed groups fed a 45% fat diet (45% kcal from fat); in utero (IU), during
lactation (LA), in utero and lactation (IU+LA), during whole life from in utero to adulthood (WL) and only as
adult (AD). The results were compared with control group on normal 10% fat diet (CTL). In mice livers, four
lipid classes to assess lipid accumulation were measured by high pressure liquid chromatography, and a
Luminex assay was applied to measure insulin-like growth factor 1 (IGF-1) protein expression in serum
samples. Further; liver samples were used to analyze the relative expression of 69 genes involved in
NAFLD signaling pathways through RT-qPCR. Mild liver steatosis (TAG above 5%) was observed in 38%
of the animals in the IU+LA and WL groups compared to none in the CTL and IU groups and 8% in LA and
AD groups. An increase of serum IGF-1 protein expression was suggested in the IU and WL groups;
indicating implication of organ growth for these groups. The gene expression analysis gave three genes
with significantly higher (p<0.05), Il10, Pparδ and Slc2a2, and four genes with borderline significantly
higher (p<0.1), Hnf4a, Insr, Tnfrsf1a and Nfe2l2 expression compared to the CTL group. These genes act
in several signaling pathways related to NAFLD, and are involved in lipid metabolism, oxidative stress,
insulin and glucose regulation, inflammation and organ developments. Thus, this study suggests a
modification of several of the major NAFLD signaling pathways in one or more of the HFD exposed groups.
The results also propose that the early life period is a phase of increased susceptibility for the risk of
development of liver steatosis and NAFLD, in line with the DOHaD hypothesis | en |
