Impact Of Low Birth Weight And High Fat Diets On Glucose Metabolism And Related Genes In Mice

Objective: To investigate whether low birth weight due to malnutri tion during pregnancy alters susceptibility to glucose abnormalities and t he changes in insulin sensitivity in adult mice exposed to a high-fat die t.Understand the regulatory changes in glucose metabolism-related gen es and explore their possible mechanisms.Methods:6-week-old mice,20 females and 10 males were randomly co-caged with a 2:1 male to female ratio after 1 week of adaptive feeding.Pregnant female mice were randomly divided into Restricted diet group and the normal diet group.The restricted diet group carried out 50 % diet restriction between 12.5 and 18.5 days of pregnancy,but a normal diet during lactation.After weaning,all mice were fed a high-fat diet(HFD).The offspring were randomly divided into low birth weight group(LBW,n=9)and normal birth weight(NBW,n=9).The weight of the mice was recorded weekly as well as the amount of food consumed.At 12 weeks of intervention,an intraperitoneal glucose tolerance test(IPGTT)was performed to measure glucose at each time point and calculate the area under the glucose curve(AUC).At 16 weeks of intervention,the activity,food intake and water intake of the mice were measured by metabolic cages for 24 hours.At 18 weeks of intervention,subcutaneous and visceral adipose tissue contents were determined by Micro CT.Mice were killed 18 weeks after the intervention and serum specimens were collected for fasting glucose and insulin.liver tissue samples were weighed and total RNA was extracted from mouse liver tissue.The expressions of adenosine monophosphate activated protein kinase(AMPK),peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1?),silent information regulator-1(SIRT1)and fibroblasts 21(FGF21)in mouse livertissue were detected by real-time quantitative PCR(RT-PCR).FGF21 protein expression was detected by Western Blotting.Results:1.Comparison of birth weight and lactation body weight between t he two groups of mice: The birth weight of mice in the LBW group(1.30± 0.07 g)was significantly lower than the NBW mice(1.66± 0.14 g),and the difference was statistically significant(P<0.05).The weight of mice in the LBW group(10.7± 1.3 g)was equal to the NBW mice(10.7± 1.4 g)at lactation.2.Comparison of food intake,water consumption and activity level between the two groups of mice: The difference in food intake between the two groups of mice was not statistically significant(P>0.05),while the metabolic cage experiment showed no statistical difference between the two groups of mice in terms of food intake,water consumption,a total distance of exercise and number of times standing(P>0.05).3.Comparison of body weight and liver weight to body weight ratio between the two groups of mice: Compared with the NBW+HFD group,mice in the LBW+HFD group had lower body weight,and the difference of body weight between the two groups was statistically significant at the 9th week(P<0.05).There was no statistical significance in the ratio of the liver weight to body weight(P>0.05).4.Comparison of experimental results of fasting blood glucose,fasting insulin and IPGTT in two groups of mice: There was no statistically significant difference in fasting insulin and AUC between the NBW+HFD group and the LBW+HFD group(P>0.05).Compared with the NBW group,fasting blood glucose and blood glucose values of 0min and 120 min were significantly increased in the LBW+HFD group,with a statistically significant difference(P<0.05).5.Comparison of subcutaneous fat and visceral fat contents in the two groups of mice: Compared with the NBW+HFD group,both subcutaneous fat and visceral fat contents in the LBW+HFD group had an increasing trend,but the difference was not statistically significant(P>0.05).6.Comparison of liver glucose metabolism-related gene m RNA and protein levels in the two groups of mice:6.1 Comparison of m RNA levels of liver glucose metabolism-relate d genes in the two groups of mice: The m RNA expression of AMPK,SIRT1 and PGC-1? in the LBW+HFD group was significantly decreased(P<0.01)and the m RNA expression of FGF21 was significantly increas ed(P<0.01)compared with the NBW+HFD group.6.2 Comparison of results of protein levels of FGF21 in the two gr oups of mice: Compared with the NBW+HFD group,the protein expres sion of FGF21 in the LBW+HFD group increased significantly(P<0.01).Conclusions:1.LBW mice were more susceptible to elevated fasting glucose and abnormal glucose tolerance in adulthood when induced by a high-fat diet.2.High-fat diet-induced glycemic disturbances in LBW adult mice were associated with altered AMPK/SIRT1/PGC-1? pathway and altered FGF21 expression.