| BackgroundIn recent years, the prevalence of obesity, hypertension, diabetes, dyslipidemia and metabolic diseases raise rapidly in an elderly Chinese population, they have become a major health problem. Developmental origins of health and disease(DOHa D) states that these diseases occur not only related to the acquired lifestyle factors but also an adverse stimulation or damage in early life growth and development. Initial studies on the thrifty phenotype hypothesis focused predominantly on the effects of maternal under-nutrition such as a diet low in protein or calories, recent studies have sought to investigate the effects of maternal over-nutrition. A maternal high fat diet can alter the development of various organs and thus the offspring become more susceptible to disease in later life. It has been shown that not only are dietary exposures during pregnancy more susceptible to those diseases but also the timing of this exposure during development. A maternal high fat and protein diet is more re?ective of the dietary habits in western countries and Chinese society. At present, there are lack of enough evidence from epidemiological studies as well as animal models about high fat and protein diet. This research focuses that the effects of high fat and protein diet in early life and dietary structure changes in later life on growth and development and metabolism of rats, and this research has great practical significance.ObjectiveThis study focuses that the effects of exposure to high fat and protein diet on maternal and lactation periods and dietary structure changes in important periods oflife on growth and development and metabolism of rats. This animal model may be provide a reasonable evidence for later diseases prevention. In the meantime, this study also provide experimental basis for enrich DOHa D.MethodsAt the start of the study, 12 male and 24 female healthy SD rats of 7 weeks of age were selected and adaptive fed for 4 weeks before the experiment. Pregnancy female rats were divided into two groups. One group was fed basic control formula feed(Con) and the other group was fed high fat and protein formula feed(HFP). Maternal rats fed formula feeds until weaning period of offspring(3 weeks after birth). Two groups of offspring were divided into three groups at 3 weeks and fed formula feeds until 14 weeks. The following three groups were Con,HPF and HPF-Con. Three groups of rats were divided into five groups at 14 weeks in adult offspring and fed formula feeds until 36 weeks. HFP offspring were randomly divided into two groups fed high fat and protein feed and low-fat feed respectively. Con offspring were randomly divided into two groups given standard basic diet and high fat and protein diet. A total of five groups were Con, Con-HFP, HFP, HFP-Con and HFP-LF. Weighing the organs of offspring at 1 day, at 3 weeks, at 14 weeks and at 36 weeks after birth accurately. The body composition and bone mineral density of rats were measured by dual energy X-ray absorptiometry in each group at 12 weeks. Weighting offspring weight from birth to 36 weeks in each group. Serum TC, TG, HDL-C and LDL-C level detected by automatic biochemical analyzer in different dietary groups. OGTT and ITT were used to evaluating glucose tolerance levels and insulin resistance levels of different dietary groups at 14 weeks and 36 weeks. HE staining for liver pathology using different groups of offspring on 21 days, 14 weeks and 36 weeks.Results1. The organ development of offspring in 1 day, at 3 weeks, 12 weeks, 14 weeks and 36 weeks study.The two groups offspring on birth weight and the organ weight ratio were no significant difference(P>0.05). At 21 days, the two groups on body weight and organ weight ratio also showed no significant difference(P>0.05).Compared with Con at 12 weeks, the bone mineral density in HFP and HFP-Con groups were lower(P<0.05). The ratio of body rat to body weight of HFP-Con male group compared with HFP were significant difference(P<0.01). Compared with Con group, the HFP group female offspring body weight and the ratio of kidney to body weight were significantly higher at 14 weeks(P<0.05), the ratio of kidney and kidney fat to body weight of HFP group male offspring were significantly higher than Con group at 14 weeks(P<0.05).Compared with Con group, female offspring of HFP group were significantly increased on body weight at 36 weeks(P<0.05). The ratio of liver, pancreas and kidney peripheral fat to body weight of HFP group were significant difference compared with Con group(P<0.05). The body weight, kidney and kidney peripheral fat of HFP-LF were significantly lower than HFP group(P<0.05).At 36 weeks male offspring development, HFP group on body weight, kidney peripheral fat and epididymis peripheral fat weight were significantly higher than Con group(P<0.05). Compared to HFP group, HFP-LF male group had lower weight on body weight, liver, brain, kidney, pancreas, kidney peripheral fat and epididymis peripheral fat(P<0.01). HF-Con group compared with HFP, HFP-Con male group on body weight, peripheral fat and epididymis peripheral fat were significantly lower(P <0.05).2. The glucose tolerance test(OGTT) of different groups offspring were born in 12 weeks and 36 weeks study.In 12 weeks study, HFP group showed statistically significant compared with Con group in the AUC of glucose tolerance test(OGTT).In 36 weeks study, the AUC value of Con-HFP and HFP female group was significantly higher the Con group, the AUC value of HFP-Con males group was significantly lower than HFP males group, the AUC value of HFP-LF both female and male groups were significantly lower than HFP group(P<0.01).3. The insulin tolerance test(ITT) of different groups offspring were born in 12 weeks and 36 weeks study.In 12 weeks study, in area under the curve(AUC) of ITT comparison, the AUC of HFP both male and female groups were significantly higher than Con group.In 36 weeks study, there was significant different in the AUC of ITT between HFP-Con males group and HFP group(P<0.05). AUC of other groups had no significantly different(P>0.05).4. The lipid levels of different groups offspring born in 14 weeks and 36 weeks study.In 14 weeks offspring study, there was significantly difference in the level of TG between HFP female group and Con female group(P<0.05). The HF-Con females group in the levels of TG, TC and LDL-C were significantly higher compared with the control group(P<0.05).In 36 weeks female offspring study, the level of TC, TG and HDL-C between HFP-LF and HFP group were significant difference(P<0.05) 。 there was no significantly difference in the levels of TC, TG, HDL-C and LDL-C in other different groups(P>0.05). In 36 weeks male offspring study, the levels of TG,HDL-C and LDL-C in HFP-LF group were significant difference than in HFP group(P<0.05).5. Pathological changes in offspring liver tissue in 3 weeks, 14 weeks and 36 weeks study.There was no significantly difference in offspring liver HE staining between Con group and HFP diet group in 21 days study. In 14 weeks study, HFP group offspring hepatocytes volume increased significantly, hepatocytes arranged in irregular, but no significant hepatic steatosis. At 36 weeks of HFP group showed that lots of hepatic steatosis under the field of vision, a lot of different size vacuoles in cytoplasmic. Con-HFP male group also showed hepatic steatosis.ConclusionsLong-term high fat and high protein diet can lead to glucose and insulintolerance decreased, and increase the possibility of adult insulin resistance and type 2 diabetes. Different dietary structure changes in adulthood had different effects on rats development and lipid and glucose metabolism, and the specific mechanism of the effects are worthy of further study. |
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