首页|Vitamin A regulates mitochondrial biogenesis and function through p38 MAPK-PGC-1α signaling pathway and alters the muscle fiber composition of sheep
Vitamin A regulates mitochondrial biogenesis and function through p38 MAPK-PGC-1α signaling pathway and alters the muscle fiber composition of sheep
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Background Vitamin A(VA)and its metabolite,retinoic acid(RA),are of great interest for their wide range of physio-logical functions.However,the regulatory contribution of VA to mitochondrial and muscle fiber composition in sheep has not been reported.Method Lambs were injected with 0(control)or 7,500 1U VA palmitate into the biceps femoris muscle on d 2 after birth.At the age of 3 and 32 weeks,longissimus dorsi(LD)muscle samples were obtained to explore the effect of VA on myofiber type composition.In vitro,we investigated the effects of RA on myofiber type composition and intrinsic mechanisms.Results The proportion of type Ⅰ myofiber was greatly increased in VA-treated sheep in LD muscle at harvest.VA greatly promoted mitochondrial biogenesis and function in LD muscle of sheep.Further exploration revealed that VA elevated PGC-1α mRNA and protein contents,and enhanced the level of p38 MAPK phosphorylation in LD muscle of sheep.In addition,the number of type Ⅰ myofibers with RA treatment was significantly increased,and type llx myofibers was significantly decreased in primary myoblasts.Consistent with in vivo experiment,RA significantly improved mitochondrial biogenesis and function in primary myoblasts of sheep.We then used si-PGC-1α to inhibit PGC-1α expression and found that si-PGC-1α significantly abrogated RA-induced the formation of type Ⅰ myofibers,mitochondrial biogenesis,MitoTracker staining intensity,UQCRC1 and ATP5A1 expression,SDH activity,and enhanced the level of type Ⅱx muscle fibers.These data suggested that RA improved mitochondrial biogenesis and function by promoting PGC-1α expression,and increased type Ⅰ myofibers.In order to prove that the effect of RA on the level of PGC-1α is caused by p38 MAPK signaling,we inhibited the p38 MAPK signaling using a p38 MAPK inhibitor,which significantly reduced RA-induced PGC-1α and MyHC Ⅰ levels.Conclusion VA promoted PGC-1α expression through the p38 MAPK signaling pathway,improved mitochondrial biogenesis,and altered the composition of muscle fiber type.
MitochondriaMuscle fiber typePGC-1αp38 MAPKRetinoic acidVitamin A
College of Animal Science,Shanxi Agricultural University,Taigu,Shanxi 030801,People's Republic of China
State Key Laboratory of Animal Nutrition and Feeding,Department of Animal Nutrition and Feed Science,College of Animal Science and Technology,China Agricultural University,Bei-jing 100193,People's Republic of China
国家自然科学基金Distinguished and Excellent Young Scholar Cultivation Project of Shanxi Agricultural University