Altered cellular redox status, sirtuin abundance and clock gene expression in a mouse model of developmentally primed NASH
| العنوان: | Altered cellular redox status, sirtuin abundance and clock gene expression in a mouse model of developmentally primed NASH |
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| المؤلفون: | Kimberley D, Bruce, Dawid, Szczepankiewicz, Kiran K, Sihota, Manoj, Ravindraanandan, Hugh, Thomas, Karen A, Lillycrop, Graham C, Burdge, Mark A, Hanson, Christopher D, Byrne, Felino R, Cagampang |
| المصدر: | Biochimica et Biophysica Acta |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | sirt1, sirtuin 1, NAFLD, non-alcoholic fatty liver disease, Aging, High fat, Photoperiod, NASH, non-alcoholic steatohepatitis, CLOCK Proteins, Receptors, Cytoplasmic and Nuclear, Development, Diet, High-Fat, Article, Mice, Sirtuin 1, NAD, nicotinamide adenine dinucleotide, Non-alcoholic Fatty Liver Disease, Pregnancy, Sirtuin 3, Fatty liver, Animals, Maternal diet, C, control, HF, high fat, Circadian, Nuclear Receptor Subfamily 1, Group F, Member 1, Clock, circadian locomotor output cycles kaput, Lipid Metabolism, Per2, Bmal1 (also called Arntl1), period 2, Circadian Rhythm, Mice, Inbred C57BL, Repressor Proteins, Cry2, cryptochrome 2, Srebp1c, sterol regulatory element binding protein-1c, Disease Models, Animal, Gene Expression Regulation, Liver, RORα, retinoic acid receptor-related orphan receptor alpha, Prenatal Exposure Delayed Effects, Nuclear Receptor Subfamily 1, Group D, Member 1, OPN, osteopontin, Female, Sterol Regulatory Element Binding Protein 1, Oxidation-Reduction, sirt3, sirtuin 3, Signal Transduction |
| الوصف: | Background We have previously shown that high fat (HF) feeding during pregnancy primes the development of non-alcoholic steatohepatits (NASH) in the adult offspring. However, the underlying mechanisms are unclear. Aims Since the endogenous molecular clock can regulate hepatic lipid metabolism, we investigated whether exposure to a HF diet during development could alter hepatic clock gene expression and contribute to NASH onset in later life. Methods Female mice were fed either a control (C, 7% kcal fat) or HF (45% kcal fat) diet. Offspring were fed either a C or HF diet resulting in four offspring groups: C/C, C/HF, HF/C and HF/HF. NAFLD progression, cellular redox status, sirtuin expression (Sirt1, Sirt3), and the expression of core clock genes (Clock, Bmal1, Per2, Cry2) and clock-controlled genes involved in lipid metabolism (Rev-Erbα, Rev-Erbβ, RORα, and Srebp1c) were measured in offspring livers. Results Offspring fed a HF diet developed NAFLD. However HF fed offspring of mothers fed a HF diet developed NASH, coupled with significantly reduced NAD+/NADH (p Highlights • Offspring of mothers fed a high fat diet show severe fatty liver in later life. • HF feeding is associated with altered cellular redox status and reduced sirtuin gene expression. • HF feeding desynchronises the expression of core clock genes and lipogenic transcription factors. • Exposure to a HF diet during development causes changes in liver metabolism that precede severe fatty liver disease. |
| تدمد: | 0006-3002 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid________::b2c49d25db7c5378cd179c13393d2008Test https://pubmed.ncbi.nlm.nih.gov/27040510Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid..........b2c49d25db7c5378cd179c13393d2008 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00063002 |
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