出生前與哺乳期西式飲食暴露對 ApoE-/- 小鼠脂質代謝之影響

余思霈

doi:10.6342/NTU201603569

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出生前與哺乳期西式飲食暴露對 ApoE-/- 小鼠脂質代謝之影響

Effects of prenatal and suckling exposure to Western diet on the lipid metabolism in ApoE-/- mice

余思霈 , Masters　　Advisor：林甫容　　

繁體中文 DOI： 10.6342/NTU201603569

高膽固醇血症；動脈粥狀硬化；脂肪肝變性；脂質代謝；胎兒規劃； hypercholesterolemia ； atherosclerosis ； hepatic steatosis ； lipid metabolism ； fetal programming

Abstract │ Reference (182) │ Times Cited (1) │ Altmetrics

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In utero environment during embryonic and fetal development is associated with risk of diseases later in life. This concept of fetal programming is further supported by clinical and experimental studies. Previous studies demonstrate that maternal high fat diet intake during early development increase susceptibility to cardiovascular diseases and liver diseases in offspring. However, little is known about the molecular mechanisms underlying the impacts of maternal diet on offspring. We aim to setup a mouse model to characterize the effects of maternal hypercholesterolemia on the lipid metabolism of adult offspring. 
Apolipoprotein E knockout (ApoE-/-) female mice were fed either a Western diet (WD) or a low-fat control diet (CD) before and during gestation and lactation. At weaning, the ApoE-/- offspring were all fed WD, generating two experimental groups: W-W and C-W offspring. Female mice gave birth to three litters. Among them, the offspring of litter 1 and 2 were analyzed at 23 weeks of age, and the offspring of litter 3 were investigated at 16 weeks of age. Biochemical analysis showed that the W-W offspring from litter 1 and 2 have a higher serum triglycerides (TG) and cholesterol levels than C-W offspring at weaning. However, there are no significant differences on hepatic TG and cholesterol levels, adipocyte area as well as the severity of atherosclerotic lesions between W-W and C-W offspring at 23 weeks of age. In contrast to the results from litter 1, and 2, more profound differences between two groups were observed in litter 3. The relative weight of liver, inguinal white adipose tissue (iWAT) and interscapular brown adipose tissue (iBAT) was significantly higher in W-W than in C-W offspring. Although there were no significant differences on the development of atherosclerotic lesions, W-W offspring from litter 3 showed hepatic steatosis combined with accumulation of hepatic TG and cholesterol in comparison with C-W group. This accumulation was associated with up-regulation of de novo lipid synthesis. Increased expressions of lipid synthesis related genes, including Fasn, Acacb, Lipe, Chpt1, Srebf1 and Srebf2 were observed in the livers of W-W offspring. In addition, the expression of cholesterol transport related genes, such as Abcg5 and Abcg8 was significantly higher in the livers of W-W in those of C-W offspring.
Taken together, our findings demonstrate that maternal hypercholesterolemia increase susceptibility to lipid accumulation in their adult offspring by augmenting hepatic lipid synthesis, which is mediated at least in part by increased expression of lipid synthesis and transport related genes. Future research will concentrate on epigenetic changes involved in this programming process.

Reference ( 182 ) 〈TOP〉

A-Gonzalez, N. et al. (2013). The Nuclear Receptor LXRα controls the functional specialization of splenic macrophages. Nature immunology, 14(8), 831-839. doi:10.1038/ni.2622
連結：
Acimovic, J. et al. (2008). CREM modulates the circadian expression of CYP51, HMGCR and cholesterogenesis in the liver. Biochem Biophys Res Commun, 376(1), 206-210. doi:10.1016/j.bbrc.2008.08.126
連結：
Agopian, V. G. et al. (2012). Liver transplantation for nonalcoholic steatohepatitis: the new epidemic. Ann Surg, 256(4), 624-633. doi:10.1097/SLA.0b013e31826b4b7e
連結：
Aharoni-Simon, M. et al. (2011). Fatty liver is associated with impaired activity of PPARgamma-coactivator 1alpha (PGC1alpha) and mitochondrial biogenesis in mice. Lab Invest, 91(7), 1018-1028. doi:10.1038/labinvest.2011.55
連結：
Aharoni-Simon, M. et al. (2011). Fatty liver is associated with impaired activity of PPARγ-coactivator 1α (PGC1α) and mitochondrial biogenesis in mice. Laboratory Investigation, 91(7), 1018-1028.
連結：

Times Cited (1) 〈TOP〉

陳誼甄(2017)。母親高膽固醇血症對小鼠子代代謝性和心血管疾病的影響。臺灣大學生化科技學系學位論文。2017。1-139。

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