基于PGC-1α/Irisin/Ucp1通路的静力性训练改善骨骼肌减少症研究进展
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摘要
基于线粒体功能紊乱与骨骼肌减少症、PGC-lα表达与线粒体功能紊乱之间的密切关系,从PGC-1α/Irisin/Ucp1通路角度阐述静力性训练改善骨骼肌减少症的作用机制研究进展。静力性训练可以诱导肌肉PGC-1α蛋白表达、促进FNDC5分解,将鸢尾素(Irisin)释放到血液中,改善线粒体功能、提高线粒体中ATP含量,辅助Ucp1在棕色脂肪和肌肉中的表达,从而降低白色脂肪含量、增加肌肉组织含量,达到抑制骨骼肌萎缩的效果。
Based on the close relationship between sarcopenia,PGC-1α expression and mitochondrial dysfunction,the mechanisms of static training on improving sarcopenia are explained from the perspective of PGC-1α/Irisin/Ucp1 pathway. Static training can induce the protein expression of PGC-1α in muscle,promote the decomposition of FNDC5,release Irisin into blood,improve the function of mitochondria,increase the ATP content in mitochondria,and assist the expression of Ucp1 in brown fat and muscle,and thus reduce the content of white fat and increase the content of muscle tissue,so as to inhibit the skeletal muscle atrophy.
Based on the close relationship between sarcopenia,PGC-1α expression and mitochondrial dysfunction,the mechanisms of static training on improving sarcopenia are explained from the perspective of PGC-1α/Irisin/Ucp1 pathway. Static training can induce the protein expression of PGC-1α in muscle,promote the decomposition of FNDC5,release Irisin into blood,improve the function of mitochondria,increase the ATP content in mitochondria,and assist the expression of Ucp1 in brown fat and muscle,and thus reduce the content of white fat and increase the content of muscle tissue,so as to inhibit the skeletal muscle atrophy.
引文
[1]CRUZ-J ENTOFT A J,LANDI F,TOPINKOVA E,et al.Understanding sarcopenia as a geriatric syndrome[J]. Curr Opin Clin Nutr Metab Care,2010,13(1):1-7.
[2]DUFOUR A B,HANNAN M T,MURABITO J M,et al. Sarcopenia definitions considering body size and fat mass are associated with mobility limitations:The Framingham Study[J]. J Gerontol A Biol Sci Med Sci,2013,68(2):168-174.
[3]NICASTRO H,ZANCHI N E,DALUZ C R,et al. Functional and morphological effects of resistance exercise on disuse-induced skeletal muscle atrophy[J]. Braz J Med Biol Res,2011,44(11):1070-1079.
[4]SUBRA J,GILLETTE-GUYONNET S,CESARI M,et al. The integration of frailty into clinical practice:preliminary results from the gérontop8e[J]. J Nutr Health Aging,2012,16(18):714-720.
[5]STUDENSKI S A,PETERS K W,ALLEY D E,et al. The FNIH sarcopenia project:rationale, study description, conference recommendations,and final estimates[J]. J Gerontol A Biol Sci Med Sci,2014,69(5):547-558.
[6]冯毅翀,邱文梅,钟国林,等.易筋经抗衰老临床研究[J].新中医,2013,45(8):106-107.
[7]苏玉凤,刘晓丹.健身气功易筋经锻炼对老年人身体机能和血脂的影响[J].南京体育学院学报,2012,11(2):27-29.
[8]金道鹏,徐俊,赵吉忠,等.推拿功法易筋经对骨骼肌减少症患者日常活动能力及体质的影响[J].中国中医药信息杂志,2011,18(1):14-16.
[9]王广兰,郑成,石爱桥,等.新编健身气功易筋经对前臂内、外侧等肌群肌电影响的研究[J].山东体育学院学报,2010,26(11):38-46.
[10]刘玉超,方磊,严隽陶,等.易筋经对老年骨骼肌减少症者生活质量的影响[J].上海中医药大学学报,2012,26(5):58-60.
[11]龚利,严隽陶,刘玉超,等.推拿功法易筋经对老年骨骼肌减少症患者等速肌力的影响[J].上海中医药大学学报,2011,25(3):55-58.
[12]方磊,刘玉超.增龄性骨骼肌减少症诊断与干预的研究现状[J].中国组织工程研究与临床康复,2009,13(2):392-395.
[13] BERRYMAN D E,CHRISTIANSEN J S,JOHANNSSON G,et al.Role of the GH/IGF1 axis in lifespan and healthspan:Lessons from animal models[J].Growth Horm IGF Res,2008,18(6):455-471.
[14]GIBALA M J,LITTLE J P,MACDONAL M J,et al. Physiological adaptations to low-volume,high-intensity interval training in health and disease[J]. J Physiol,2012,590(5):1077-1084.
[15]CHUNG H Y,LEE E K,CHOI Y J,et al. Molecular inflammation as an underlying mechanism of the aging process and age-related diseases[J]. J Dent Res,2011,90(7):830-840.
[16] PETERSON C M,JOHANNSEN D L,RAVUSSIN E. Skeletal muscle mitochondria and aging:a review[J]. J Aging Res,2012,2012:194821. doi:10.1155/2012/194821.
[17] O’NEILL E D,WILDING J P,KAHN C R,et al. Absence of insulin signaling in skeletal muscle is associated with reduced muscle mass and function:evidence for decreased protein synthesis and not increased degradation[J]. Age(Dordr),2010,32(2):209-222.
[18]CHAI R J,VUKOVIC J,DUNLOP S,et al. Striking denervation of neuromuscular junctions without lumbar motoneuron loss in geriatric mouse muscle[J]. PLoS One,2011,6(12):e28090.
[19] AAGAARD P,SUETTA C,CASEROTTI P,et al. Role of the nervous system in sarcopenia and muscle atrophy with aging:strength training as a countermeasure[J]. Scand J Med Sci Sports,2010,20(1):49-64.
[20] SUZUKI N,MOTOHASHI N,UEZUMI A,et al. NO production results in suspension-induced muscle atrophy through dislocation of neuronal NOS[J]. J Clin Invest,2007,117(9):2468-2476.
[21] REEVES N D,NARICI M B,MAGANARIS C N. Myotendinous plasticity to aging and resistance exercise in humans[J]. Exp Physiol,2006,91(3):483-498.
[22]LIU X G,TAN L J,LEI S F,et al. Genome-wide association and replication studies identified TBHR as an important gene for lean body mass[J]. Am J Hum Genet,2009,84(3):418-423.
[23]CALVANI R,JOSEPH A M,ADHIHETTY P J,et al. Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy[J]. Biol Chem,2013,394(3):393-414.
[24]ARTHUR P G,GROUNDS M D,SHAVLAKADZE T. Oxidative stress as a therapeutic target during muscle wasting:considering the complex interactions[J]. Curr Opin Clin Nutr Metab Care,2008,11(4):408-416.
[25]PROLLA T A,DENU J M. NAD(+)deficiency in age-related mitochondrial dysfunction[J]. Cell Metab,2014,19(2):178-180.
[26]FULLE S,Di DONNA S D,PUGLIELLI C,et al. Age dependent imbalance of antioxidative system in human satellite cells[J]. Exp Gerontol,2005,40(3):189-197.
[27]EMANUELE M,RICCARDO C,MATTEO C,et al. Mitochondrial dysfunction and sarcopenia of aging:from signaling pathways to clinical trials[J]. Int J Biochem Cell Biol,2013,45(10):2288-2301.
[28]RAJHANS R,NAIR H B,NAIR S S,et al. Modulation of in situ estrogen synthesis by proline-,glutamic acid-,and leucine-rich protein-1:potential estrogen receptor autocrine signaling loop in breast cancer cells[J]. Mol Endocrinol,2008,22(3):649-664.
[29]HAILEY D W,RAMBOLD A S,SATPUTE K P,et a1.Mitochondria supply membranes for autophagoseme biogenesis during starvation[J]. Cell,2010,141(4):656-667.
[30]赵永军,卢健.骨骼肌自噬的调控机制与Sarcopenia的关联及运动的影响[J].中国运动医学杂志,2013,32(10):929-935.
[31] SCARPULLA R. Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network[J]. Biochim Biophys Acta,2011,1813(7):1269-1278.
[32]BOSTROM P,WU J,JEDRYCHOWSKI M P,et al. A PGC1-alphadependent myokine that drives brown-fat-like development of white fat and thermogenesis[J].Nature,2012,481(7382):463-468.
[33]DILLON L M,REBELO A P,MORAES C T. The role of PGC-1coactivators in aging skeletal muscle and heart[J]. IUBMB Life,2012,64(3):231-241.
[34] SCARPULLA R. Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network[J]. Biochim Biophys Acta,2011,1813(7):1269-1278.
[35]GENG T,LI P,OKUTSU M,et al. PGC-1αplays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle[J]. Am J Physiol Cell Physiol,2010,298(3):572-579.
[36]GIBALA M J,MCGEE S L,GARNHAM A P,et al. Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1 alpha in human skeletal muscle[J]. J Appl Physiol,2009,106(3):929-934.
[37]BRAULT J J,JESPERSEN J G,GOLDBERG A L. Peroxisome proliferator-activated receptor gamma coactivator 1alpha or 1beta overexpression inhibits muscle protein degradation,induction of ubiquitin ligases,and disuse atrophy[J]. J Biol Chem,2010,285(25):19460-19471.
[38]DERBRE F,GOMEZ-CABRERA M C,NASCIMENTO A L,et al.Age associated low mitochondrial biogenesis may be explained by lack of response of PGC-1 alpha to exercise training[J]. Age(Dordr),2012,34(3):669-679.
[39]宋立稳,逢力男.Irisin:一种诱导脂肪组织转化的肌因子[J].中华临床医师杂志,2013,7(13):6057-6058.
[40]HUH J Y,PANAGIOTOU G,MOUGIOS V,et al. FNDC5 and irisin in humans:I. Predictors of circulating concentrations in serum and plasma and II. m RNA expression and circulating concentrations in response to weight loss and exercise[J]. Metabolism,2012,61(12):1725-1738.
[41]CANNON B,NEDERGARD J. Nonshivering thermogenesis and its adequate measurement in metabolic studies[J]. J Exp Biol,2011,214(pt2):242-253.
[42] VILLARROYA F. Irisin,turning up the heat[J]. Cell Metab,2012,15(3):277-278.
[43]LIDELL M E,ENERBACK S.Brown adipose tissue—a new role in humans[J]. Nat Rev Endocrinol,2010,6(6):319-325.
[44]CASTILLO-QUAN J I. From white to brown fat through the PGC1-alpha-dependent myokine irisin:implications for diabetes and obesity[J]. Dis Model Mech,2012,5(3):293-295.
[45]VIRTANEN K A,LIDELL M E,ORAVA J,et al. Functional brown adipose tissue in healthy adults[J]. N Engl J Med,2009,360(15):1518-1525.
[46] ANA O M,MANUEL S. PTEN in cancer,metabolism and aging[J]. Trends Endocrinol Metab,2013,24(4):184-189.
[47] SCICCHITANO B M,RIZZUTO E,MUSARO A. Counteracting muscle wasting in aging and neuromuscular diseases:the critical role of IGF-1[J]. Aging(Albany NY),2009,1(5):451-457.
[48]PARK K,GROSS M,LEE D H,et al. Oxidative Stress and Insulin Resistance:The Coronary Artery Risk Development in Young Adultsstudy[J]. Diabetes Care,2009,32(7):1302-1307.
[49]SANCHIS-GOMAR F,PEREZ-QUILIS C. The p38-PGC-1alphairisin-betatrophinaxis:Exploring new pathways in insulin resistance[J]. Adipocyte,2014,3(1):67-68.
[2]DUFOUR A B,HANNAN M T,MURABITO J M,et al. Sarcopenia definitions considering body size and fat mass are associated with mobility limitations:The Framingham Study[J]. J Gerontol A Biol Sci Med Sci,2013,68(2):168-174.
[3]NICASTRO H,ZANCHI N E,DALUZ C R,et al. Functional and morphological effects of resistance exercise on disuse-induced skeletal muscle atrophy[J]. Braz J Med Biol Res,2011,44(11):1070-1079.
[4]SUBRA J,GILLETTE-GUYONNET S,CESARI M,et al. The integration of frailty into clinical practice:preliminary results from the gérontop8e[J]. J Nutr Health Aging,2012,16(18):714-720.
[5]STUDENSKI S A,PETERS K W,ALLEY D E,et al. The FNIH sarcopenia project:rationale, study description, conference recommendations,and final estimates[J]. J Gerontol A Biol Sci Med Sci,2014,69(5):547-558.
[6]冯毅翀,邱文梅,钟国林,等.易筋经抗衰老临床研究[J].新中医,2013,45(8):106-107.
[7]苏玉凤,刘晓丹.健身气功易筋经锻炼对老年人身体机能和血脂的影响[J].南京体育学院学报,2012,11(2):27-29.
[8]金道鹏,徐俊,赵吉忠,等.推拿功法易筋经对骨骼肌减少症患者日常活动能力及体质的影响[J].中国中医药信息杂志,2011,18(1):14-16.
[9]王广兰,郑成,石爱桥,等.新编健身气功易筋经对前臂内、外侧等肌群肌电影响的研究[J].山东体育学院学报,2010,26(11):38-46.
[10]刘玉超,方磊,严隽陶,等.易筋经对老年骨骼肌减少症者生活质量的影响[J].上海中医药大学学报,2012,26(5):58-60.
[11]龚利,严隽陶,刘玉超,等.推拿功法易筋经对老年骨骼肌减少症患者等速肌力的影响[J].上海中医药大学学报,2011,25(3):55-58.
[12]方磊,刘玉超.增龄性骨骼肌减少症诊断与干预的研究现状[J].中国组织工程研究与临床康复,2009,13(2):392-395.
[13] BERRYMAN D E,CHRISTIANSEN J S,JOHANNSSON G,et al.Role of the GH/IGF1 axis in lifespan and healthspan:Lessons from animal models[J].Growth Horm IGF Res,2008,18(6):455-471.
[14]GIBALA M J,LITTLE J P,MACDONAL M J,et al. Physiological adaptations to low-volume,high-intensity interval training in health and disease[J]. J Physiol,2012,590(5):1077-1084.
[15]CHUNG H Y,LEE E K,CHOI Y J,et al. Molecular inflammation as an underlying mechanism of the aging process and age-related diseases[J]. J Dent Res,2011,90(7):830-840.
[16] PETERSON C M,JOHANNSEN D L,RAVUSSIN E. Skeletal muscle mitochondria and aging:a review[J]. J Aging Res,2012,2012:194821. doi:10.1155/2012/194821.
[17] O’NEILL E D,WILDING J P,KAHN C R,et al. Absence of insulin signaling in skeletal muscle is associated with reduced muscle mass and function:evidence for decreased protein synthesis and not increased degradation[J]. Age(Dordr),2010,32(2):209-222.
[18]CHAI R J,VUKOVIC J,DUNLOP S,et al. Striking denervation of neuromuscular junctions without lumbar motoneuron loss in geriatric mouse muscle[J]. PLoS One,2011,6(12):e28090.
[19] AAGAARD P,SUETTA C,CASEROTTI P,et al. Role of the nervous system in sarcopenia and muscle atrophy with aging:strength training as a countermeasure[J]. Scand J Med Sci Sports,2010,20(1):49-64.
[20] SUZUKI N,MOTOHASHI N,UEZUMI A,et al. NO production results in suspension-induced muscle atrophy through dislocation of neuronal NOS[J]. J Clin Invest,2007,117(9):2468-2476.
[21] REEVES N D,NARICI M B,MAGANARIS C N. Myotendinous plasticity to aging and resistance exercise in humans[J]. Exp Physiol,2006,91(3):483-498.
[22]LIU X G,TAN L J,LEI S F,et al. Genome-wide association and replication studies identified TBHR as an important gene for lean body mass[J]. Am J Hum Genet,2009,84(3):418-423.
[23]CALVANI R,JOSEPH A M,ADHIHETTY P J,et al. Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy[J]. Biol Chem,2013,394(3):393-414.
[24]ARTHUR P G,GROUNDS M D,SHAVLAKADZE T. Oxidative stress as a therapeutic target during muscle wasting:considering the complex interactions[J]. Curr Opin Clin Nutr Metab Care,2008,11(4):408-416.
[25]PROLLA T A,DENU J M. NAD(+)deficiency in age-related mitochondrial dysfunction[J]. Cell Metab,2014,19(2):178-180.
[26]FULLE S,Di DONNA S D,PUGLIELLI C,et al. Age dependent imbalance of antioxidative system in human satellite cells[J]. Exp Gerontol,2005,40(3):189-197.
[27]EMANUELE M,RICCARDO C,MATTEO C,et al. Mitochondrial dysfunction and sarcopenia of aging:from signaling pathways to clinical trials[J]. Int J Biochem Cell Biol,2013,45(10):2288-2301.
[28]RAJHANS R,NAIR H B,NAIR S S,et al. Modulation of in situ estrogen synthesis by proline-,glutamic acid-,and leucine-rich protein-1:potential estrogen receptor autocrine signaling loop in breast cancer cells[J]. Mol Endocrinol,2008,22(3):649-664.
[29]HAILEY D W,RAMBOLD A S,SATPUTE K P,et a1.Mitochondria supply membranes for autophagoseme biogenesis during starvation[J]. Cell,2010,141(4):656-667.
[30]赵永军,卢健.骨骼肌自噬的调控机制与Sarcopenia的关联及运动的影响[J].中国运动医学杂志,2013,32(10):929-935.
[31] SCARPULLA R. Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network[J]. Biochim Biophys Acta,2011,1813(7):1269-1278.
[32]BOSTROM P,WU J,JEDRYCHOWSKI M P,et al. A PGC1-alphadependent myokine that drives brown-fat-like development of white fat and thermogenesis[J].Nature,2012,481(7382):463-468.
[33]DILLON L M,REBELO A P,MORAES C T. The role of PGC-1coactivators in aging skeletal muscle and heart[J]. IUBMB Life,2012,64(3):231-241.
[34] SCARPULLA R. Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network[J]. Biochim Biophys Acta,2011,1813(7):1269-1278.
[35]GENG T,LI P,OKUTSU M,et al. PGC-1αplays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle[J]. Am J Physiol Cell Physiol,2010,298(3):572-579.
[36]GIBALA M J,MCGEE S L,GARNHAM A P,et al. Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1 alpha in human skeletal muscle[J]. J Appl Physiol,2009,106(3):929-934.
[37]BRAULT J J,JESPERSEN J G,GOLDBERG A L. Peroxisome proliferator-activated receptor gamma coactivator 1alpha or 1beta overexpression inhibits muscle protein degradation,induction of ubiquitin ligases,and disuse atrophy[J]. J Biol Chem,2010,285(25):19460-19471.
[38]DERBRE F,GOMEZ-CABRERA M C,NASCIMENTO A L,et al.Age associated low mitochondrial biogenesis may be explained by lack of response of PGC-1 alpha to exercise training[J]. Age(Dordr),2012,34(3):669-679.
[39]宋立稳,逢力男.Irisin:一种诱导脂肪组织转化的肌因子[J].中华临床医师杂志,2013,7(13):6057-6058.
[40]HUH J Y,PANAGIOTOU G,MOUGIOS V,et al. FNDC5 and irisin in humans:I. Predictors of circulating concentrations in serum and plasma and II. m RNA expression and circulating concentrations in response to weight loss and exercise[J]. Metabolism,2012,61(12):1725-1738.
[41]CANNON B,NEDERGARD J. Nonshivering thermogenesis and its adequate measurement in metabolic studies[J]. J Exp Biol,2011,214(pt2):242-253.
[42] VILLARROYA F. Irisin,turning up the heat[J]. Cell Metab,2012,15(3):277-278.
[43]LIDELL M E,ENERBACK S.Brown adipose tissue—a new role in humans[J]. Nat Rev Endocrinol,2010,6(6):319-325.
[44]CASTILLO-QUAN J I. From white to brown fat through the PGC1-alpha-dependent myokine irisin:implications for diabetes and obesity[J]. Dis Model Mech,2012,5(3):293-295.
[45]VIRTANEN K A,LIDELL M E,ORAVA J,et al. Functional brown adipose tissue in healthy adults[J]. N Engl J Med,2009,360(15):1518-1525.
[46] ANA O M,MANUEL S. PTEN in cancer,metabolism and aging[J]. Trends Endocrinol Metab,2013,24(4):184-189.
[47] SCICCHITANO B M,RIZZUTO E,MUSARO A. Counteracting muscle wasting in aging and neuromuscular diseases:the critical role of IGF-1[J]. Aging(Albany NY),2009,1(5):451-457.
[48]PARK K,GROSS M,LEE D H,et al. Oxidative Stress and Insulin Resistance:The Coronary Artery Risk Development in Young Adultsstudy[J]. Diabetes Care,2009,32(7):1302-1307.
[49]SANCHIS-GOMAR F,PEREZ-QUILIS C. The p38-PGC-1alphairisin-betatrophinaxis:Exploring new pathways in insulin resistance[J]. Adipocyte,2014,3(1):67-68.