Effects Of Diet Control And Exercise On Osteocalcin Signal Transduction And Testosterone Biosynthesis In Male Mice

Objective: Osteocalcin is non-collagen protein synthesized and secreted by osteoblasts,its main function is affecting and regulating the bone metabolism by regulating the mineralization rate of bone,but the studies in recent years show that it can regulate the energy metabolism,and it is closely related to the reproductive function.Obesity can cause androgen disorder,and effective fat reduction can improve the androgen disorder,but the action mechanism is unclear.This study takes high-fat diet to induce mice obesity sex hormone disorder,use three intervention ways such as exercise,diet and exercise combined diet to reduce fat,discuss the influence of obesity and three intervention ways on synthesis of osteocalcin and testosterone of male mice,in order to provide the experimental basis for the molecular mechanism of energy balance regulation of male reproductive function.Methods: Four-week-old C57 BL mice were divided into two groups randomly: the normal control(NC)was given basal feed;the obese control(OBC)was given high-fat diet;10 weeks later,the obese model mice was divided into groups including obese controls,obese exercise(OE),obese diet control(ODC)and obese diet exercise(ODE)according to weight stratification random sampling.Aerobic exercise intervention was performed in the OE and ODE groups.The ODC and ODE groups were fed70% of the diet intake in the high-fat control group.After 8 weeks of intervention,the mice's body weight,testis,abdominal fat weight,serum testosterone(T),and osteocalcin(OCN)were measured.And the G protein-coupled receptor GPRC6 A,cyclic adenosine monophosphate(cAMP),cAMP response element binding protein(CREB),steroid acute regulatory protein(StAR),cholesterol side chain lyase in mouse testis(P450scc)gene expression levels and protein expression were tested.The data is expressed by ± SD.SPSS statistical software was used for analysis of variance between groups.Results:1.Morphological indicators of mice: Compared with the normal control,the body weight,body fat and body fat tend of mice in the obese control increased(P<0.001),and the testicular coefficient decreased(P<0.001),showing a significant difference.Compared with the obese control,the body weights of the obese diet control,obese exercise and obese diet exercise were significantly decreased(P<0.01),and the body fat tend was significantly decreased(P<0.05 or P< 0.05),testicular coefficient all significantly increased(P <0.05 or P <0.01).Compared with the obese diet exercise,the body weight and body fat tend in the obese diet control and obese exercise decreased,and the body fat tend increased,showing a significant difference(P<0.01).2.Blood index: Compared with the normal control,the serum testosterone and osteocalcin levels of mice in the obese control were decreased,and the level of estradiol(E2)was increased,and there was a significant difference(P<0.01).Compared with the obese control,the levels of serum testosterone andosteocalc in the obese exercise,obesey diet control and obese diet exercise were significantly increased(P < 0.05 or P <0.05),and the levels of serum estradiol significantly decreased(P < 0.05 or P<0.01).Compared with the obese exercise,the levels of serum testosterone and osteocalcin in the obese diet exercise were decreased,and the level of estradiol(E2)was increased,and there was a significant difference(P<0.01).Compared with the obese exercise,the levels of serum testosterone and osteocalcin in the obese diet control were decreased significantly,and there was no significant differences among the levels of serum estradiol,in the obese diet control(P > 0.05).3.mRNA expression and protein expression: Compared with the normal control,the StAR,P450 scc,GPRC6A,cAMP,and CREB mRNA and protein expression in the obese control were significantly decreased(P<0.01).Compared with obese control,the transcription and protein expression of StAR,P450 scc,GPRC6A,cAMP,and CREB mRNA in the obese diet control,obese exercise and obese diet exercise were significantly decreased(P<0.01 or P<0.05).Conclusion:1.The decrease of serum osteocalcin in male obese mice induced by long-term high-fat diet may inhibit the mRNA and protein expression of GPRC6A-cAMP-StAR/P450 scc signaling pathway in testis tissue,which influences the biosynthesis of testosterone,and thus the occurrence of sex hormone disorder.2.The treadmill exercise,dietary intervention,and exercise combined diet of 8 weeks can effectively reduce the weight and body fat,improve the obese of mice and up-regulate serum osteocalcin levels,improving the GPRC6A-cAMP-StAR/P450 scc signaling pathway and improve obesity-induced low blood testosterone.The exercise without other interventions was the best for improving the level of osteocalcin and sex hormone.