Abstract
We investigated the regulation of hepatic ER stress in healthy liver and adult or perinatally programmed diet-induced non-alcoholic fatty liver disease (NAFLD). Female mice were fed either obesogenic or control diet before mating, during pregnancy and lactation. Post-weaning, offspring from each maternal group were divided into either obesogenic or control diet. At six months, offspring were sacrificed at 4-h intervals over 24 h. Offspring fed obesogenic diets developed NAFLD phenotype, and the combination of maternal and offspring obesogenic diets exacerbated this phenotype. UPR signalling pathways (IREα, PERK, ATF6) and their downstream regulators showed different basal rhythmicity, which was modified in offspring exposed to obesogenic diet and maternal programming. The double obesogenic hit increased liver apoptosis measured by TUNEL staining, active caspase-3 and phospho-JNK and GRP78 promoter methylation levels. This study demonstrates that hepatic UPR is rhythmically activated. The combination of maternal obesity (MO) and obesogenic diets in offspring triggered altered UPR rhythmicity, DNA methylation and cellular apoptosis.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, which ranges from bland steatosis to steatohepatitis (NASH), cirrhosis and potentially hepatocellular carcinoma (HCC) (Farrell & Larter 2006)
Offspring exposed to maternal obesity and post-natal obesogenic diets developed profound NAFLD phenotype
Post-weaning developed a profound obesity-associated NAFLD phenotype, characterised by higher liver weight (Figure 1(B)), NAS score (Figure 1(D)) and hepatic triglyceride content (Figure 1(C,F)), in comparison to offspring exposed to post-partum obesogenic diet only (OffCon-OD)
Summary
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, which ranges from bland steatosis to steatohepatitis (NASH), cirrhosis and potentially hepatocellular carcinoma (HCC) (Farrell & Larter 2006). It is the leading cause of chronic liver disease in the Western world with a prevalence rising in parallel to obesity. The prevalence of NAFLD has more than doubled over the last two decades, affecting approximately 11% of adolescents (Welsh et al 2013). The precise molecular mechanisms of programming in NAFLD pathogenesis remain unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: International Journal of Food Sciences and Nutrition
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
