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.

• Klíčová slova
• ER stress, NAFLD, Obesity, circadian rhythm, developmental programming,
• MeSH
• chaperon endoplazmatického retikula BiP MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• endoplazmatické retikulum fyziologie   MeSH
• fyziologický stres účinky léků   MeSH
• homeostáza MeSH
• játra účinky léků   MeSH
• krmivo pro zvířata analýza   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• obezita chemicky indukované   metabolismus   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH