Effects Of Hypoxia Training Combined With Magnesium Supplementation On Hepatic Lipid Metabolic Disorders In Obesemice

Objective:Hypoxia training has positive effect on weight loss.Magnesium,as an activator of various enzymatic reactions,participates in various metabolic reactions.However,it is unclear whether magnesium plays an important role in improving lipid metabolism disorders in hypoxia training reducing body weight.The purpose of this study was to establish a highfat diet-induced obese mice model and to explore the effect of hypoxia training combined with magnesium supplementation on weight loss and hepatic lipid metabolism disorders in obese mice.Methodlogy:90 4-week-old C57 BL/6J male mice were selected.After adaptive feeding for 1 week,the mice were randomly divided into standard diet group(SD,n=20)and highfat diet group(HFD,n=70),respectively,to give standard diet and highfat diet(D12492,fat energy accounted for 60%)for 12 weeks.The body weight of mice was measured every week.After 12 weeks of highfat diet,The mice whose body weight was more than 20% of the mean value of control mice were considered as obese mice.Some of the obese mice weresacrificed used for obese model validation.After the obese model was established,obese mice were randomly divided into obesity control group(OB,n=9,highfat diet,without any intervention),training group(T,n=9,training at night:14m/min,60min/d,6d/w),hypoxia exposure group(H,n=9,hypoxia exposure during the day: mice were exposed to 14.4% oxygen at 1 atmosphere absolute for 8h/d,6d/w;training at night:14m/min,60min/d,6d/w),hypoxia training group(HT,n=9,hypoxia exposure combined with training protocol),magnesium supplementation group(Mg,n=9,in drinking water,magnesium doses of 100mg/kg/d),hypoxia training combined with magnesium supplementation(HT+Mg,n=9,hypoxia training combined with magnesium supplementation protocol).All groups underwent an intervention for 4 weeks;at the same time,a normal diet control group(CON,n=10,standard diet,without any intervention)was established.At the end of 4 weeks after the intervention,the mice were sacrificed and the serum,erythrocyte,left and right femurs,left and right epididymal fat,left and right perirenal fat,and livers were collected.The mice body weight changes and body fat ratio were calculated;glucose oxidase-peroxidase method was used to detect the fasting blood glucose levels in mice;ELISA was used to detectconcentrationof blood lipids,serum ATGL,CPT-1 andFFA levels in livers;detection concentrationof erythrocyte,femurs magnesium by ICP-AES;RT-qPCR assay mice livers related lipid metabolism enzyme mRNA expression levels.Results: 1.Establish a highfat dietinduced obese mouse modelAfter 12-week highfat diet,the results showed that the body fat ratio in the HFD group was significantly greater than that in the SD group(P<0.01);the FBG(P<0.01)and serum LDL(P<0.01)were significantly higher in the HFD group than in the SD group;liver weight in HFD group were significantly greater than SD group(P<0.01),and liver FFA levels were significantly higher than SD group(P<0.01);2.Effects of hypoxia training on body weight loss in obese miceAfter 4 weeks of hypoxia training intervention,compared with OB group,body weights of mice in T(P<0.01),H(P<0.01),and HT(P<0.01)groups were significantly decreased,the greatest decrease in HT group was observed.Compared with OB group,the body fat ratio in mice of H(P<0.01)and HT(P<0.05)groups was significantly decreased,and the FBG in mice of H(P<0.01)and HT(P<0.01)groups was significant decline;3.Effects of hypoxia training on magnesium metabolism in obese miceAfter 4 weeks of hypoxia training intervention,the erythrocyte magnesium status in the HT group were significantly lower than that in the OB group(P<0.01).Compared with the CON group,the femur magnesium statusin the OB(P<0.01)and HT(P<0.01)groups decreased significantly;there were a significant negative correlation between magnesium status in the femur and body weight(P<0.01)and body fat(P<0.01);4.Effects of hypoxia training combined with magnesium supplementation on weight loss and hepatic lipid metabolism in obese miceAfter 4 weeks of intervention,compared with OB group,body weight of mice in HT(P<0.01),Mg(P<0.01),and HT+Mg(P<0.01)groups were significantly decreased,the greatest decrease in HT and HT+Mg groups was observed;compared with OB group,the ratio of body fat in HT(P<0.01),Mg(P<0.01),and HT+Mg(P<0.01)groups was significantly decreased;The FBG was significantly lower in the HT(P<0.01)and HT+Mg(P<0.01)groups than in the OB group;the liver weight(P<0.05)and liver FFA levels(P<0.01)were significantly lower in the HT+Mg group than in the OB group.The levels of serum ATGL(P<0.01)and CPT-1(P<0.01)in HT+Mg groups were significantly higher than those in OB group.Compared with OB group,expression of liver ATGL mRNA in HT+Mg group was significantly increased(P<0.01);compared with OB group,the expression of PPARα mRNA was significantly increased in HT(P<0.01)and HT+Mg(P<0.01)groups;Mg(P<0.01),HT+Mg(P<0.05)of liver LPL mRNA expression was significantly higher than OB and HT group;the expression of CPT-1A mRNA was significantly higher in HT+Mg group than in OB(P<0.01)and HT(P<0.01)group;Conclusions:1.Compared with simply exercise training or hypoxia exposure,hypoxia training is more effective in weight loss,and hypoxia training can also help reduce the fasting blood glucose;2.Obesity and hypoxia training exacerbate magnesium loss,indicating the importance of magnesium supplementation in losing weight by hypoxia training;3.In the process of weight loss in hypoxia training combined with magnesium supplementation,helpful to increase that mRNA expression of the PPARα and its related lipid metabolism enzyme,promoting oxidation of fatty acid in liver,improve hepatic lipid metabolic disorders in obese mice.