The Study On The Effect Of Ketogenic Diet On Regular Growth And Classical High Fat Diet On Sirt1 Pathway In Rodents

IntroductionIt has been approved that the composition and components of diet can not only alter physical function, but also regulate some susceptible genes. The adipocytes can reflect any change in diet sensitively.The ketogenic diet, a special high-fat-low-carbohydrate diet with long history in successfully controlling intractable seizures, has been used body weight management recently. A number of investigations have reported significant weight loss in individuals adhering to a ketogenic diet in obesity and overweight people with metabolic syndrome or hyperlipid problems. But in real life there are many normal people facing body weight management problem, it is not clear how the ketogenic diet will affect normal organism.The studies on dietary fat on susceptible genes are attracting more and more attention. SIRT1, an NAD~+-dependent protein in nucleus, is involved in many metabolic reactions. Some experiments before focused on caloric restriction in long life, people know little about the relationship between Sirt1 and obesity.We observed the effect of ketogenic diet on regular growth in rodents and classic high fat diet on Sirt1 pathway in obesity prone and resistant rats.Experimental ProceduresMale Wistar rats (n=23) were divided into ketogenic group or control group randomly by body weight. After 10 days' acclimation, the rats in control group continued eating normal chow ad libitum, while the ketogenic group rats were fed ketogenic diet with same energy as the control group rats consumed everyday. After 10 days' pair feeding, all rats were exercised in running wheels. The training phase lasted 3 weeks, then performance test were carried out. Respiratory quotient (RQ) and energy expenditure (EE) via indirect calorimetry system were measured before and during pair feeding period, post exercise and performance test phase. All animals were pair fed throughout the investigation to ensure that both groups consumed an equicaloric diet. At the end of the investigation all animals were decapitated and trunk blood was extracted. Radioimmunal assay was performed to evaluate insulin level.30 new weaned Wistar rats were divided into two groups. 20 rats were fed classical high fat diet, the other 10 were fed normal chow ad libitum for 4 weeks. At the end the intervention, those rat fed with high fat diet were sorted by body weight, the up one third were regarded as obesity prone (OP), and the down one third were regarded as obesity resist (OR). All animals were decapitated, all inguinal fat and epididymis fat were extracted and weighed, some subcutaneous fat was also extracted, all fat tissue samples were stored in -70℃. Semi-quantification of Sirt1 mRNA, FOXO1 mRNA and PPARγmRNA was performed by using RT-PCR. PPARγprotein level was compared by Western-blot assay.Results1. Under pair feeding conditions, consuming a ketogenic diet resulted in a lack of bodyweight gain in comparison to weight matched animals consuming regular laboratory chow. The difference of total protein quantity between ketogenic group and control group was little, while albumin level in ketogenic diet group was significantly higher than control group rats. Purified ketogenic diet intervention reduced serum cholesterol and insulin level, but raised serum triglyceride. Although energy intake was reduced during daily exercise training, but which didn't retard normal growth. A decline in RQ following 4 days exposure to the diet was observed, through fat utilization was higher during exercise in the ketogenic diet fed animals in comparison to chow fed animals, whilst EE did not differ. No differences were observed in exercise capacity between the groups.2. Classical high fat diet induced obesity prone and obesity resistant rats, body weight differed significantly between groups. Semi-quantification analysis that, there was no significant difference between OP and OR rats when comparing the Sirt1mRNA, FOXO1mRNA and PPARγmRNA , while the two groups' level were significantly lower than control group's. We didn't observe significant PPARγprotein difference between OP and OR rats either. High fat diet induced fewer PPARγprotein in subcutaneous fat tissue, but more PPARγprotein in inguinal and epididymis fat tissue.Conclusion1. The current investigation demonstrates that consumption of a very low CHO ketogenic diet results in significant changes to body weight in younger and older animals under pair feeding conditions. Despite consuming the same amount of energy the animals in the ketogenic diet group weighed less following the intervention. Changes to RQ were observed following four days consumption of the ketogenic diet, thus indicating metabolic adaptation. Consuming a ketogenic diet did not affect exercise capacity in rodents. This coupled with the fact that EE was elevated following exercise may point to the fact that consuming a ketogenic diet plus a structured exercise regime may be an effective tool for the treatment of obesity in some individuals. However, to further understand the effects of consuming a ketogenic diet, analysis of body composition and various blood parameters are yet to be performed.2. Classical high fat high energy intake could decrease mRNA expression of Sirt1,FOXO1 and PPARγ. Regulating Sirt1/ FOXO1 might be potent goal for prevent and treating obesity.3. Feeding classical high fat diet induced more fat deposit in viscera.