Effects of Hypoxia Exercise Induced miR-27/PPARγ on Fatty Acids Metabolism in Gastrocnemius of Obese Rat
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Graphical Abstract
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Abstract
Objective: To explore the effects of hypoxic exercise on miR-27/PPARγ and lipid metabolism related gene and protein expression levels in gastrocnemius muscle of obese rats. Methods: The high-fat diet induced obese rats were randomly divided into 5 groups (n=10 in each group) , i.e., a normal oxygen concentration group (C) , a hypoxia-exercises-for-1-week group (E1) , a hypoxiaexercises-for-2-weeks group (E2) , a hypoxia-exercises-for-3-weeks group (E3) and a hypoxia-exercises-for-4-weeks group (E4) . The exercise training was conducted in an environment of 13.6% hypoxic (equivalent to the actual altitude of 3500 meters high oxygen content) , rats were running on an animal treadmill in a speed of 20 m/min for 1 h/d, 5 d/w. After 24 h of the last exercise (12 h fasting) , the middle of the right gastrocnemius muscle was collected. The RT-PCR was used to detect the mRNA levels of miR-27, PPARγ, CD36 and ATGL, the protein levels of PPARγ, CD36 and ATGL were measured by using Western blotting. Results: 1) In the first two weeks, the expression levels of miR-27 was gradually decreased in gastrocnemius muscle, but it was gradually increased in the subsequent two weeks. The expression levels of miR-27 in group E4 were significantly higher than other groups (P<0.01) . 2) The mRNA levels of PPARγ were gradually increased during the training session, but the mRNA levels of PPARγ in group E3 were significantly lower than that of group E1 and E2 (P<0.05) , and group E4 (P<0.01) ; the group C was significantly lower than group E4 as well (P<0.05) ; the protein levels of PPARγ showed a trend from decline to rise during training session, both group C and E1 were significantly higher than group E2、E3 and E4 (P<0.01) , the group of E2 was significantly lower than E3 group (P<0.05) and E4 group (P<0.01) . 3) The mRNA levels of ATGL in group C were significantly lower than E1、E2、E3 and E4 groups (P<0.01) , and the group E3 was significantly lower than group E4 (P<0.01) ; moreover, the protein levels of ATGL were lower in group C and E1 than that of group E3 (P<0.01) and group E4 (P<0.05) ; 4) The mRNA levels of CD36 in group C were significantly higher than group E2 and E3 (P<0.05) , the group E1 was significantly higher than group E2 as well (P<0.05) . The protein levels of CD36 in group C was significantly lower than group E2 and E3 (P<0.05) . Conclusion: The miR-27 in skeletal muscle of obese rats was increased significantly at the fourth week of hypoxic exercise training. miR-27 regulates the transcription and translation of target genes in the downstream of PPARγ, thereby regulates the lipid metabolism in rats, and this is the potential molecular mechanism of hypoxic exercise in reducing body fat and weight.
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