| Background Low birth weight is still prevalent in developing countries because of low prepregnancy weight and poor gestational nutrition. In both animal and clinical researches, it was suggested that low birth weight and intrauterine growth retardation were associated with hyperlipidemia in later life. Moreover, this association was enhanced after being exposed to postnatal unfavorable environment, such as high-fat diets. Therefore, dyslipidemia in the later life may come from the interaction between prenatal and postnatal environment. The mechanisms by which prenatal development exerts its effect on the lipid metabolism in later life were not completely understood. It was suggested that this effect may come from changes in the transcriptional regulation of related fat acid synthesis and oxidation, cholesterol synthesis and transformation. Additionally, intervention of diets in the adult animals with intrauterine growth retardation have suggested that intrauterine growth retardation animals were more susceptible to high fat diets. Another studies of fish oil in the intrauterine growth retardation rats have confirmed the benefit of lipid metabolism which was regulated by related genes. However, there was still no related researches focused on the interaction between IUGR and postnatal diets intervention in young adult rats.Objective To study the effects of IUGR and post-weaning diets on the liver lipid metabolism were studied in offspring, and their interaction. Looking into the mechanisms that regulating synthesis and oxidation of fatty acid, synthesis and transformation of cholesterol in liver. Methods IUGR model was built by restricting intake of pregnancy rats. After weaning in21days, thirty-six IUGR offspring and forty-eight control offspring were allocated to three diets:standard chow (10%fat), fish oil diet (10%fat) and high fat diet (45%fat). At10weeks, we performed the following measurements in offspring:fasting plasma glucose test, serum triglycerides and total cholesterol test, liver histopathological examination, and PCR of related gene in liver.Results (1)At birth, IUGR offspring showed lower weight (4.31±0.06g) than control offspring (6.74±0.07g), and there was statistically significant (P<0.01). At weaning, IUGR offspring (55.97±1.00g) was still lighter than control offspring (62.79±0.97g). At10-week, both control and IUGRspring showed more weight gains under high fat diet.(2)At10-week, compared to control rats, the liver of IUGR offspring showed microvesicular steatosis. Fish oil diet decreased the microvesicular steatosis in the liver cells, but high fat diet showed significantly increased macrovesicular steatosis in both control and IUGR offspring.(3)Fasting plasma glucose, serum triglycerides and total cholesterol were decreased in IUGR offspring (P<0.05). There were no significant alteration of serum lipids under high fat diet, but significant reduction under fish oil diet.(4)At10-week, the expressions of PGC-la, CPT-1, HMGR, SREBP-2and SREBP-1were downregulated in IUGR offspring. In fish oil diet groups, the expressions of ACC-1were downregulated, while the expressions of LDLR and CPT-1were upregulated. In high fat diet groups, the expressions of SREBP-1, SREBP-2and PPARy were upregulated.Conclusion In yound adult rats, IUGR offspring tended to develop lipid metabolism disorder in liver and hyperlipidemia. Under high fat diet, IUGR offspring developed steatosis in hepatocytes before alteration in serum lipids. Early fish oil may be beneficial to prevent from hyperglycemia and hyperlipidemia, which may be regulated by related genes of fatty acid synthesis and oxidation. |
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