| First Author | Bruce KD | Year | 2016 |
| Journal | Biochim Biophys Acta | Volume | 1861 |
| Issue | 7 | Pages | 584-93 |
| PubMed ID | 27040510 | Mgi Jnum | J:251052 |
| Mgi Id | MGI:6104772 | Doi | 10.1016/j.bbalip.2016.03.026 |
| Citation | Bruce KD, et al. (2016) Altered cellular redox status, sirtuin abundance and clock gene expression in a mouse model of developmentally primed NASH. Biochim Biophys Acta 1861(7):584-93 |
| abstractText | 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-Erbalpha, Rev-Erbbeta, RORalpha, 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<0.05, HF/HF vs C/C), Sirt1 (p<0.001, HF/HF vs C/C), Sirt3 (p<0.01, HF/HF vs C/C), perturbed clock gene expression, and elevated expression of genes involved lipid metabolism, such as Srebp1c (p<0.05, C/HF and HF/HF vs C/C). CONCLUSION: Our results suggest that exposure to excess dietary fat during early and post-natal life increases the susceptibility to develop NASH in adulthood, involving altered cellular redox status, reduced sirtuin abundance, and desynchronized clock gene expression. |
