Maternal High Fat Diet Increases The Risk Of Metabolic Disease In F2 Generation And Its Mechanism Exploration

Objectives: To observe the impact of maternal high fat diet on body metabolism in F2 generations and explore its mechanism.Methods: Establishing an animal model of maternal high fat diet,and evaluating the glycolipid metabolic parameters and liver histopathology by HE staining and oil red O staining between two groups at birth,3 weeks of age and 12 weeks of age in F2 generation.Real-Time PCR was then used to assess the mRNA gene expression involved in liver lipid metabolism and inflammation at 3 weeks of age and 12 weeks of age.In addition,accessing the proliferation of insulin by using Ki67/Insulin immunofluorescence double staining method at 3 weeks of age and 12 weeks of age.The expression of insulin gene and insulin transcript factors were analyzed by real-time PCR and Western blotting.Results: The body weight in experimental group was significantly heavier than that in control group.The levels of glycolipid metabolic parameters were significantly higher in experimental group at 3 weeks of age and 12 weeks of age.The HE and oil red O staining in experimental group showed an exaggerated form of diet-induced fatty liver.Compared to the control group,the expression of Fasn,Acaca and PPAR-? decreased in experimental group at 3 weeks of age.Meanwhile,the expression of PPAR-?,Cpt1?and Acsl3 also decreased.In addition,the expression of Fasn,PPAR-?,PPAR-? and Ehhadh were down-regulated in experimental group at 12 weeks of age.Tough there were no significant difference on hepatic gene expression involved in inflammation between two groups.The proliferation of insulin were decreased in experimental group both at 3 weeks of age and 12 weeks of age.At 12 weeks of age,the expression of Pdx1,NeuroD1 mRNA were significantly decreased in experimental group.Pdx1 protein expression remarkably declines in experimental group.Conclusions: Maternal high fat diet represses the mRNA expression of genes involved in endogenous lipogenesis and the expression of genes involved in lipid oxidation.Maternal high fat diet can also reduce the expression of insulin gene transcript factors Pdx1 and NeuroD1,and then induce increased body weight,increased glycolipid metabolic parameters and fatty liver in F2 generation.