| Objective: To compare the differences of glucose and lipid metabolism and the level of hypothalamic histone modification in mice fed the different durations of high-fat diet,and to provide reference for further study of energy metabolism disorders such as obesity and diabetes.Methods: One hundred and fifty SPF male C57BL/6 mice with body weight of18-20 g and age of 5-6 weeks were utilized.After one week of adaptive feeding in SPF room,the mice were randomly divided into 5 groups according to their body weight and given different diet :(1)chow diet for 12 weeks(3M Chow group);(2)chow diet for 8 weeks and then high fat diet for 4 weeks(1M HFD group);(3)high fat diet for 12 weeks(3M HFD group);(4)chow diet for 24 weeks(6M Chow group);(5)high fat diet for 24 weeks(6M HFD group).Body weight was measured every 3 days.Five to seven mice in each group were randomly selected for ITT,GTT and Wheel Running experiments.The remaining mice were sacrificed and serum was prepared.At the same time,the hypothalamus,liver,epididymal fat and subcutaneous fat were collected and weighed,and cryopreserved in the-80 °C refrigerator.Results: 1.For body weight,wet weight of subcutaneous adipose tissue,white adipose tissue and liver,3M HFD group was higher than 1M HFD group(P<0.05),1M HFD group was higher than 3M Chow group(P <0.05),6M HFD group was higher than 6M Chow group(P<0.05),6M HFD group was higher than 3M HFD group(P <0.05).2.Wheel Running activity: 3M HFD group was higher than 1M HFD group(P <0.05),1M HFD group was higher than 3M Chow group(P<0.05),6M HFD group was higher than 6M Chow group(P<0.05),6M HFD group was higher than 3M HFD group(P<0.05).3.Blood chemistry.The comparison of serum TC and LDL-C levels: 1 HFD group and 3M HFD group were higher than 3M Chow group(P <0.05),6M HFD group was higher than 6M Chow group(P<0.05).The comparison of serum TG and insulin levels: 3M HFD group was higher both than 3M Chow group and 1M HFD group(P<0.05),6M HFD group was higher both than 6M Chow group and 3M HFD group(P<0.05).The comparison of serum FBG,random blood glucose,leptin levels:1M HFD group and 3M HFD group were higher than 3M Chow group(P <0.05),6M HFD group was higher than 6M Chow group(P<0.05),6M HFD group had an increasing trend compared to 1M HFD group(0.05 <P<0.1).4.The comparison of glucose tolerance and insulin sensitivity with the area under the blood glucose curve of GTT and ITT: 1M HFD group and 3M HFD group were higher than 3M Chow group(P <0.05),6M HFD group was higher than 3M HFD group(P<0.05).5.The comparison of the levels of histone methyltransferase G9 a,Mll1,Ezh1 in hypothalamus: the level of G9 a in 6M HFD group had a downward trend compared to 6M Chow group(0.05<P<0.1),the Ezh1 level in 3M HFD group was higher both than 3M Chow group and 6M HFD group(P <0.05),the Mll1 level of 6M HFD group was lower both than 6M Chow group and 3M HFD group(P<0.05).6.The comparison of the levels of hypothalamic histone H3 modification:H3K4me3 level was higher in 3M Chow group than that in 3M HFD group(P<0.05),H3K27me3 levels in both 3M Chow group and 6M HFD group were higher than that in 3M HFD group(P<0.05),the H3K36me3 level in 6M HFD group had an increasing trend compared to 3M HFD group(0.05 <P <0.1).In addition,the level of histone acetylation modification H3K27 ac in 6M HFD group had a decreasing trend relative to 6M Chow group(0.05 <P <0.1).Conclusions:(1)High fat diet treatment can significantly increase the body weights and body fat contents of mice,and reduce the spontaneous activity.(2)Mice fed 1month of high fat diet already showed blood glucose and lipid metabolism disorders.With prolonged high fat diet treatment,the blood glucose and lipid metabolism disorders had been deteriorated.(3)High fat diet affect the level of histone modification enzyme and histone H3 modification in hypothalamus,suggesting that the occurrence and development of obesity and obesity-related complications may be related to the changes of histone modification levels in hypothalamus. |
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