β-Hydroxy-β-methylbutyrate, mitochondrial biogenesis, and skeletal muscle health

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• 作者：Xi He ; Yehui Duan ; Kang Yao ; Fengna Li ; Yongqing Hou ; Guoyao Wu ; Yulong Yin
• 关键词：β ; Hydroxy ; β ; methylbutyrate ; Mitochondrial biogenesis ; Fiber ; type transformation ; Skeletal muscle health
• 刊名：Amino Acids
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：48
• 期：3
• 页码：653-664
• 全文大小：735 KB
• 参考文献：Ahn BH, Kim HS, Song SW et al (2008) A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci USA 105:14447–14452PubMedCentral PubMed CrossRef
  Aquilano K, Vigilanza P, Baldelli S et al (2010) Peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha) and sirtuin 1 (SIRT1) reside in mitochondria possible direct function in mitochondrial biogenesis. J Biol Chem 285:21590–21599PubMedCentral PubMed CrossRef
  Arany Z, Novikov M, Chin S et al (2006) Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-γ coactivator 1α. Proc Natl Acad Sci USA 103:10086–10091PubMedCentral PubMed CrossRef
  Aspnes LE, Lee CM, Weindruch R et al (1997) Caloric restriction reduces fiber loss and mitochondrial abnormalities in aged rat muscle. FASEB J 11:573–581PubMed
  Bazer FW, Ying W, Wang XQ et al (2015) The many faces of interferon tau. Amino Acids 47:449–460PubMed CrossRef
  Berchtold MW, Brinkmeier H, Muntener M (2000) Calcium ion in skeletal muscle: its crucial role for muscle function, plasticity, and disease. Physiol Rev 80:1215–1265PubMed
  Bruckbauer A, Zemel MB (2013) Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity. Diabetes Metab Syndr Obes 6:93–102PubMedCentral PubMed
  Buler M, Aatsinki SM, Izzi V et al (2014) SIRT5 is under the control of PGC-1alpha and AMPK and is involved in regulation of mitochondrial energy metabolism. FASEB J 28:3225–3237PubMed CrossRef
  Calvo S, Venepally P, Cheng J et al (1999) Fiber-type-specific transcription of the troponin l slow gene is regulated by multiple elements. Mol Cell Biol 19:515–525PubMedCentral PubMed CrossRef
  Calvo JA, Daniels TG, Wang X et al (2008) Muscle-specific expression of PPARγ coactivator-1α improves exercise performance and increases peak oxygen uptake. J Appl Physiol 104:1304–1312PubMed CrossRef
  Canto C, Gerhart-Hines Z, Feige JN et al (2009) AMPK regulates energy expenditure by modulating NAD(+) metabolism and SIRT1 activity. Nature 458:1056–1060PubMedCentral PubMed CrossRef
  Canto C, Jiang LQ, Deshmukh AS et al (2010) Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab 11:213–219PubMedCentral PubMed CrossRef
  Chalkiadaki A, Igarashi M, Nasamu AS et al (2014) Muscle-specific SIRT1 gain-of-function increases slow-twitch fibers and ameliorates pathophysiology in a mouse model of duchenne muscular dystrophy. PLoS Genet 10:e1004490PubMedCentral PubMed CrossRef
  Cheng W, Phillips B, Abumrad N (1997) Beta-hydroxy-beta-methyl butyrate increases fatty acid oxidation by muscle cells. FASEB J 11:A381
  Cheng W, Phillips B, Abumrad N (1998) Effect of HMB on fuel utilization, membrane stability and creatine kinase content of cultured muscle cells. FASEB J 12:A950
  Clark RH, Feleke G, Din M et al (2000) Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study. JPEN J Parenter Enteral Nutr 24:133–139PubMed CrossRef
  Columbus DA, Fiorotto ML, Davis TA (2015) Leucine is a major regulator of muscle protein synthesis in neonates. Amino Acids 47:259–270PubMedCentral PubMed CrossRef
  Crabtree GR, Olson EN (2002) NFAT signaling: choreographing the social lives of cells. Cell 109(2):S67–S79PubMed CrossRef
  Dai ZL, Wu ZL, Yang Y et al (2013) Nitric oxide and energy metabolism in mammals. BioFactors 39:383–391PubMed CrossRef
  D’Antona G, Ragni M, Cardile A et al (2010) Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice. Cell Metab 12:362–372PubMed CrossRef
  Davis TA, Suryawan A, Orellana RA et al (2010) Amino acids and insulin are regulators of muscle protein synthesis in neonatal pigs. Animal 4:1790–1796PubMedCentral PubMed CrossRef
  de Moura MB, dos Santos LS, Van Houten B (2010) Mitochondrial dysfunction in neurodegenerative diseases and cancer. Environ Mol Mutagen 51:391–405PubMed
  Demling RH (2009) Nutrition, anabolism, and the wound healing process: an overview. Eplasty 9:e9PubMedCentral PubMed
  Drey M (2011) Sarcopenia—pathophysiology and clinical relevance. Wien Med Wochenschr 161:402–408PubMed CrossRef
  Duan Y, Li F, Li Y et al (2015a) The role of leucine and its metabolites in protein and energy metabolism. Amino Acids. doi:10.​1007/​s00726-015-2067-1
  Duan YH, Li FN, Liu HN et al (2015b) Nutritional and regulatory roles of leucine in muscle growth and fat reduction. Front Biosci Landmark 20:796–813CrossRef
  Duan YH, Li FN, Tan KR et al (2015c) Key mediators of intracellular amino acids signaling to mTORC1 activation. Amino Acids 47:857–867PubMed CrossRef
  Duchen MR (2004) Roles of mitochondria in health and disease. Diabetes 53:S96–S102PubMed CrossRef
  Eddinger TJ, Moss RL (1987) Mechanical-properties of skinned single fibers of identified types from rat diaphragm. Am J Physiol 253:C210–C218PubMed
  Eley HL, Russell ST, Baxter JH et al (2007) Signaling pathways initiated by beta-hydroxy-beta-methylbutyrate to attenuate the depression of protein synthesis in skeletal muscle in response to cachectic stimuli. Am J Physiol Endocrinol Metab 293:E923–E931PubMed CrossRef
  Eley HL, Russell ST, Tisdale MJ (2008a) Mechanism of attenuation of muscle protein degradation induced by tumor necrosis factor-alpha and angiotensin II by beta-hydroxy-beta-methylbutyrate. Am J Physiol Endocrinol Metab 295:E1417–E1426PubMed CrossRef
  Eley HL, Russell ST, Tisdale MJ (2008b) Attenuation of depression of muscle protein synthesis induced by lipopolysaccharide, tumor necrosis factor, and angiotensin II by beta-hydroxy-betamethylbutyrate. Am J Physiol Endocrinol Metab 295:E1409–E1416PubMed CrossRef
  Ennion S, Pereira JS, Sargeant AJ et al (1995) Characterization of human skeletal-muscle fibers according to the myosin heavy-chains they express. J Muscle Res Cell Motil 16:35–43PubMed CrossRef
  Evans M, Rees A (2002) Effects of HMG-CoA reductase inhibitors on skeletal muscle: are all statins the same? Drug Saf 25:649–663PubMed CrossRef
  Feldman JL, Dittenhafer-Reed KE, Denu JM (2012) Sirtuin catalysis and regulation. J Biol Chem 287:42419–42427PubMedCentral PubMed CrossRef
  Figueiredo PA, Powers SK, Ferreira RM et al (2009) Aging impairs skeletal muscle mitochondrial bioenergetic function. J Gerontol A Biol Sci Med Sci 64:21–33PubMed CrossRef
  Filhiol TM (2012) The effects of leucine on mitochondrial biogenesis and cell cycle in A-375 melanoma cells, Master Thesis. The University of Tennessee, Knoxville
  Fillmore N, Jacobs DL, Mills DB et al (2010) Chronic AMP-activated protein kinase activation and a high-fat diet have an additive effect on mitochondria in rat skeletal muscle. J Appl Physiol 109:511–520PubMedCentral PubMed CrossRef
  Fu WJ, Haynes TE, Kohli R et al (2005) Dietary l -arginine supplementation reduces fat mass in Zucker diabetic fatty rats. J Nutr 135:714–721PubMed
  Gerhart-Hines Z, Rodgers JT, Bare O et al (2007) Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1 alpha. EMBO J 26:1913–1923PubMedCentral PubMed CrossRef
  Gouspillou G, Sgarioto N, Norris B et al (2014) The relationship between muscle fiber type-specific PGC-1 alpha content and mitochondrial content varies between rodent models and humans. PLoS One 9:e103044PubMedCentral PubMed CrossRef
  Handschin C, Chin S, Li P et al (2007) Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle-specific knock-out animals. J Biol Chem 282:30014–30021PubMed CrossRef
  Hardie DG, Ross FA, Hawley SA (2012) AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol 13:251–262PubMed CrossRef
  Hirschey MD, Shimazu T, Goetzman E et al (2010) SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 464:121–125PubMedCentral PubMed CrossRef
  Hock MB, Kralli A (2009) Transcriptional control of mitochondrial biogenesis and function. Annu Rev Physiol 71:177–203PubMed CrossRef
  Horton MJ, Brandon CA, Morris TJ et al (2001) Abundant expression of myosin heavy-chain IIB RNA in a subset of human masseter muscle fibres. Arch Oral Biol 46:1039–1050PubMedCentral PubMed CrossRef
  Horvath TL, Erion DM, Elsworth JD et al (2011) GPA protects the nigrostriatal dopamine system by enhancing mitochondrial function. Neurobiol Dis 43:152–162PubMedCentral PubMed CrossRef
  Hou YQ, Wang L, Yi D et al (2015a) N-acetylcysteine and intestinal health: a focus on mechanisms of its actions. Front Biosci 20:872–891CrossRef
  Hou YQ, Yin YL, Wu G (2015b) Dietary essentiality of “nutritionally nonessential amino acids” for animals and humans. Exp Biol Med 240:997–1007CrossRef
  Huss JM, Torra IP, Staels B et al (2004) Estrogen-related receptor alpha directs peroxisome proliferator-activated receptor at signaling in the transcriptional control of energy metabolism in cardiac and skeletal muscle. Mol Cell Biol 24:9079–9091PubMedCentral PubMed CrossRef
  Jager S, Handschin C, St-Pierre J et al (2007) AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA 104:12017–12022PubMedCentral PubMed CrossRef
  Jobgen WS, Fried SK, Fu WJ et al (2006) Regulatory role for the arginine-nitric oxide pathway in metabolism of energy substrates. J Nutr Biochem 17:571–588PubMed CrossRef
  Johnston APW, De Lisio M, Parise G (2008) Resistance training, sarcopenia, and the mitochondrial theory of aging. Appl Physiol Nutr Metab 33:191–199PubMed CrossRef
  Joseph AM, Joanisse DR, Baillot RG et al (2012) Mitochondrial dysregulation in the pathogenesis of diabetes: potential for mitochondrial biogenesis-mediated interventions. Exp Diabetes Res. doi:10.​1155/​2012/​642038 PubMedCentral PubMed
  Jowko E, Ostaszewski P, Jank M et al (2001) Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program. Nutrition 17:558–566PubMed CrossRef
  Karagounis LG, Hawley JA (2010) Skeletal muscle: increasing the size of the locomotor cell. Int J Biochem Cell Biol 42:1376–1379PubMed CrossRef
  Kim JS, Wilson JM, Lee SR (2010) Dietary implications on mechanisms of sarcopenia: roles of protein, amino acids and antioxidants. J Nutr Biochem 21:1–13PubMed CrossRef
  Kong X, Wang R, Xue Y et al (2010) Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis. PLoS One 5:e11707PubMedCentral PubMed CrossRef
  Kovarik M, Muthny T, Sispera L et al (2010) Effects of beta-hydroxy-beta-methylbutyrate treatment in different types of skeletal muscle of intact and septic rats. J Physiol Biochem 66:311–319PubMed CrossRef
  Koves TR, Li P, An J et al (2005) Peroxisome proliferator-activated receptor-gamma co-activator 1alpha-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency. J Biol Chem 280:33588–33598PubMed CrossRef
  Lage R, Dieguez C, Vidal-Puig A et al (2008) AMPK: a metabolic gauge regulating whole-body energy homeostasis. Trends Mol Med 14:539–549PubMed CrossRef
  Leone TC, Lehman JJ, Finck BN et al (2005) PGC-1α deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol 3:e101PubMedCentral PubMed CrossRef
  Li F, Yin Y, Tan B et al (2011) Leucine nutrition in animals and humans: mTOR signaling and beyond. Amino Acids 41:1185–1193PubMed CrossRef
  Li HL, Xu MJ, Lee J et al (2012) Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice. Am J Physiol Endocrinol Metab 303:E1234–E1244PubMedCentral PubMed CrossRef
  Liang C, Curry BJ, Brown PL et al (2014) Leucine modulates mitochondrial biogenesis and SIRT1-AMPK signaling in C2C12 myotubes. J Nutr Metab 2014:239750PubMedCentral PubMed CrossRef
  Lin J, Wu H, Tarr PT et al (2002) Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418:797–801PubMed CrossRef
  Lombard DB, Alt FW, Cheng HL et al (2007) Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol 27:8807–8814PubMedCentral PubMed CrossRef
  McKnight JR, Satterfield MC, Jobgen WS et al (2010) Beneficial effects of l -arginine on reducing obesity: potential mechanisms and important implications for human health. Amino Acids 39:349–357PubMed CrossRef
  Molfino A, Gioia G, Rossi Fanelli F et al (2013) Beta-hydroxy-beta-methylbutyrate supplementation in health and disease: a systematic review of randomized trials. Amino Acids 45:1273–1292PubMed CrossRef
  Mootha VK, Bunkenborg J, Olsen JV et al (2003) Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria. Cell 115:629–640PubMed CrossRef
  Murgia M, Serrano AL, Calabria E et al (2000) Ras is involved in nerve-activity-dependent regulation of muscle genes. Nat Cell Biol 2:142–147PubMed CrossRef
  Narkar VA, Downes M, Yu RT et al (2008) AMPK and PPARdelta agonists are exercise mimetics. Cell 134:405–415PubMedCentral PubMed CrossRef
  Naya FJ, Mercer B, Shelton J et al (2000) Stimulation of slow skeletal muscle fiber gene expression by calcineurin in vivo. J Biol Chem 275:4545–4548PubMed CrossRef
  Nissen SL, Abumrad NN (1997) Nutritional role of the leucine metabolite β-hydroxy β-methylbutyrate (HMB). J Nutr Biochem 8:300–311CrossRef
  Nissen SL, Sharp RL (2003) Effect of dietary supplements on lean mass and strength gains with resistance exercise: a meta-analysis. J Appl Physiol 94:651–659PubMed CrossRef
  Nissen S, Sharp R, Ray M et al (1996) Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training. J Appl Physiol 81:2095–2104PubMed
  Noh KK, Chung KW, Choi YJ et al (2014) Beta-hydroxy-beta-methylbutyrate improves dexamethasone-induced muscle atrophy by modulating the muscle degradation pathway in SD rat. PLoS One 9:e102947PubMedCentral PubMed CrossRef
  Olson EN, Williams RS (2000) Remodeling muscles with calcineurin. BioEssays 22:510–519PubMed CrossRef
  Pagliarini DJ, Calvo SE, Chang B et al (2008) A mitochondrial protein compendium elucidates complex I disease biology. Cell 134:112–123PubMedCentral PubMed CrossRef
  Pansarasa O, Flati V, Corsetti G et al (2008) Oral amino acid supplementation counteracts age-induced sarcopenia in elderly rats. Am J Cardiol 101:35e–41ePubMed CrossRef
  Panton LB, Rathmacher JA, Baier S et al (2000) Nutritional supplementation of the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) during resistance training. Nutrition 16:734–739PubMed CrossRef
  Pette D, Hofer HW (1979) The constant proportion enzyme group concept in the selection of reference enzymes in metabolism. Ciba Found Symp 73:231–244PubMed
  Pette D, Staron RS (2001) Transitions of muscle fiber phenotypic profiles. Histochem Cell Biol 115:359–372PubMed
  Pimentel GD, Rosa JC, Lira FS et al (2011) Beta-hydroxy-beta-methylbutyrate (HMbeta) supplementation stimulates skeletal muscle hypertrophy in rats via the mTOR pathway. Nutr Metab (Lond) 8:11CrossRef
  Poyton RO, McEwen JE (1996) Crosstalk between nuclear and mitochondrial genomes. Annu Rev Biochem 65:563–607PubMed CrossRef
  Price NL, Gomes AP, Ling AJY et al (2012) SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab 15:675–690PubMedCentral PubMed CrossRef
  Prince FP, Hikida RS, Hagerman FC et al (1981) A morphometric analysis of human-muscle fibers with relation to fiber types and adaptations to exercise. J Neurol Sci 49:165–179PubMed CrossRef
  Rasbach KA, Gupta RK, Ruas JL et al (2010) PGC-1alpha regulates a HIF2alpha-dependent switch in skeletal muscle fiber types. Proc Natl Acad Sci USA 107:21866–21871PubMedCentral PubMed CrossRef
  Rivero JLL, Talmadge RJ, Edgerton VR (1998) Fibre size and metabolic properties of myosin heavy chain-based fibre types in rat skeletal muscle. J Muscle Res Cell Motil 19:733–742PubMed CrossRef
  Rodgers JT, Lerin C, Haas W et al (2005) Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 434:113–118PubMed CrossRef
  Rodgers JT, Lerin C, Gerhart-Hines Z et al (2008) Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett 582:46–53PubMedCentral PubMed CrossRef
  Russell ST, Tisdale MJ (2009) Mechanism of attenuation by beta-hydroxy-beta-methylbutyrate of muscle protein degradation induced by lipopolysaccharide. Mol Cell Biochem 330:171–179PubMed CrossRef
  Russell AP, Foletta VC, Snow RJ et al (2014) Skeletal muscle mitochondria: a major player in exercise, health and disease. Biochim Biophys Acta 1840:1276–1284PubMed CrossRef
  Sahin E, Colla S, Liesa M et al (2011) Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 470:359–365PubMedCentral PubMed CrossRef
  Scarpulla RC (2008) Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 88:611–638PubMed CrossRef
  Scarpulla RC (2011) Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Bba-Mol Cell Res 1813:1269–1278
  Scheffler TL, Scheffler JM, Park S et al (2014) Fiber hypertrophy and increased oxidative capacity can occur simultaneously in pig glycolytic skeletal muscle. Am J Physiol Cell Physiol 306:C354–C363PubMed CrossRef
  Shaw RJ, Kosmatka M, Bardeesy N et al (2004) The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci USA 101:3329–3335PubMedCentral PubMed CrossRef
  Slater GJ, Jenkins D (2000) Beta-hydroxy-beta-methylbutyrate (HMB) supplementation and the promotion of muscle growth and strength. Sports Med 30:105–116PubMed CrossRef
  Smerdu V, Karschmizrachi I, Campione M et al (1994) Type-iix myosin heavy-chain transcripts are expressed in type iib fibers of human skeletal-muscle. Am J Physiol Cell Physiol 267:C1723–C1728
  Smith HJ, Wyke SM, Tisdale MJ (2004) Mechanism of the attenuation of proteolysis-inducing factor stimulated protein degradation in muscle by β-hydroxy-β-methylbutyrate. Cancer Res 64:8731–8735PubMed CrossRef
  Smith HJ, Mukerji P, Tisdale MJ (2005) Attenuation of proteasome-induced proteolysis in skeletal muscle by β-hydroxy-β-methylbutyrate in cancer-induced muscle loss. Cancer Res 65:277–283PubMed CrossRef
  Solerte SB, Fioravanti M, Locatelli E et al (2008) Improvement of blood glucose control and insulin sensitivity during a long-term (60 weeks) randomized study with amino acid dietary supplements in elderly subjects with type 2 diabetes mellitus. Am J Cardiol 101:82e–88ePubMed CrossRef
  Stancliffe RA (2012) Role of beta-hydroxy-beta-methylbutyrate (HMB) in leucine stimulation of mitochondrial biogenesis and fatty acid oxidation, Master Thesis. The University of Tennessee, Knoxville
  Stefano GB, Kim C, Mantione K et al (2012) Targeting mitochondrial biogenesis for promoting health. Med Sci Monit 18:Sc1-Sc3
  Sun X, Zemel MB (2009) Leucine modulation of mitochondrial mass and oxygen consumption in skeletal muscle cells and adipocytes. Nutr Metab (Lond) 6:26CrossRef
  Sun YL, Wu ZL, Li W et al (2015) Dietary l -leucine supplementation enhances intestinal development in suckling piglets. Amino Acids 47:1517–1525PubMed CrossRef
  Tekwe CD, Lei J, Yao K et al (2013) Oral administration of interferon tau enhances oxidation of energy substrates and reduces adiposity in Zucker diabetic fatty rats. BioFactors 39:552–563PubMed CrossRef
  Termin A, Staron RS, Pette D (1989) Myosin heavy chain isoforms in histochemically defined fiber types of rat muscle. Histochemistry 92:453–457PubMed CrossRef
  Valerio A, D’Antona G, Nisoli E (2011) Branched-chain amino acids, mitochondrial biogenesis, and healthspan: an evolutionary perspective. Aging-Us 3:464–478
  Vaughan RA, Garcia-Smith R, Gannon NP et al (2013) Leucine treatment enhances oxidative capacity through complete carbohydrate oxidation and increased mitochondrial density in skeletal muscle cells. Amino Acids 45:901–911PubMed CrossRef
  Venhoff N, Lebrecht D, Pfeifer D et al (2012) Muscle-fiber transdifferentiation in an experimental model of respiratory chain myopathy. Arthritis Res Ther 14:1–11CrossRef
  Verdijk LB, Snijders T, Beelen M et al (2010) Characteristics of muscle fiber type are predictive of skeletal muscle mass and strength in elderly men. J Am Geriatr Soc 58:2069–2075PubMed CrossRef
  Virbasius CA, Virbasius JV, Scarpulla RC (1993) NRF-1, an activator involved in nuclearmitochondrial interactions, utilizes a new DNA-binding domain conserved in a family of developmental regulators. Genes Dev 7:2431–2445PubMed CrossRef
  Vukovich MD, Stubbs NB, Bohlken RM (2001) Body composition in 70-year-old adults responds to dietary beta-hydroxy-beta-methylbutyrate similarly to that of young adults. J Nutr 131:2049–2052PubMed
  Wallace DC (2010) Mitochondrial DNA mutations in disease and aging. Environ Mol Mutagen 51:440–450PubMed
  Wang YX, Zhang CL, Yu RT et al (2004) Regulation of muscle fiber type and running endurance by PPARdelta. PLoS Biol 2:e294PubMedCentral PubMed CrossRef
  Weber TA, Reichert AS (2010) Impaired quality control of mitochondria: aging from a new perspective. Exp Gerontol 45:503–511PubMed CrossRef
  Wenz T, Rossi SG, Rotundo RL et al (2009) Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging. Proc Natl Acad Sci USA 106:20405–20410PubMedCentral PubMed CrossRef
  Wilson GJ, Wilson JM, Manninen AH (2008) Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: a review. Nutr Metab (Lond) 5:1CrossRef
  Wolfe RR (2006) The underappreciated role of muscle in health and disease. Am J Clin Nutr 84:475–482PubMed
  Wu G (2013) Amino acids: biochemistry and nutrition. CRC Press, Boca RatonCrossRef
  Wu ZD, Puigserver P, Andersson U et al (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124PubMed CrossRef
  Wu H, Naya FJ, Mckinsey TA et al (2000) MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type. EMBO J 19:1963–1973PubMedCentral PubMed CrossRef
  Wu H, Rothermel B, Kanatous S et al (2001) Activation of MEF2 by muscle activity is mediated through a calcineurin-dependent pathway. EMBO J 20:6414–6423PubMedCentral PubMed CrossRef
  Wu H, Kanatous SB, Thurmond FA et al (2002) Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science 296:349–352PubMed CrossRef
  Wu G, Bazer FW, Dai ZL, Li DF, Wang JJ, Wu ZL (2014) Amino acid nutrition in animals: protein synthesis and beyond. Annu Rev Anim Biosci 2:387–417PubMed CrossRef
  Yan Z, Okutsu M, Akhtar YN et al (2011) Regulation of exercise-induced fiber type transformation, mitochondrial biogenesis, and angiogenesis in skeletal muscle. J Appl Physiol 110:264–274PubMedCentral PubMed CrossRef
  Yang Y, Wu ZL, Meininger CJ et al (2015) L-Leucine and NO-mediated cardiovascular function. Amino Acids 47:435–447PubMed CrossRef
  Yi D, Hou YQ, Wang L et al (2015) L-Glutamine enhances enterocyte growth via activation of the mTOR signaling pathway independently of AMPK. Amino Acids 47:65–78PubMed CrossRef
  Yin YL, Yao K, Liu ZJ et al (2010) Supplementing l -leucine to a low-protein diet increases tissue protein synthesis in weanling pigs. Amino Acids 39:1477–1486PubMed CrossRef
  Zanchi NE, Gerlinger-Romero F, Guimaraes-Ferreira L et al (2011) HMB supplementation: clinical and athletic performance-related effects and mechanisms of action. Amino Acids 40:1015–1025PubMed CrossRef
  Zhang D, Mott JL, Farrar P et al (2003) Mitochondrial DNA mutations activate the mitochondrial apoptotic pathway and cause dilated cardiomyopathy. Cardiovasc Res 57:147–157PubMed CrossRef
  Zierath JR, Hawley JA (2004) Skeletal muscle fiber type: influence on contractile and metabolic properties. PLoS Biol 2:1523–1527CrossRef
  
• 作者单位：Xi He (1) (2)
  Yehui Duan (3) (4)
  Kang Yao (1) (3)
  Fengna Li (3)
  Yongqing Hou (5)
  Guoyao Wu (3) (5) (6)
  Yulong Yin (1) (3) (5)
  
  1. College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China
  2. Hunan Co-Innovation Center of Animal Production Safety, Changsha, 410128, China
  3. Scientific Observation and Experiment Station of Animal Nutrition and Feed Science in South-Central China, Ministry of Agriculture, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, No. 644 Yuanda Road, Furong District, Changsha, 410125, Hunan, China
  4. University of Chinese Academy of Sciences, Beijing, 100039, China
  5. Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China
  6. Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Analytical Chemistry
  Biochemical Engineering
  Life Sciences
  Proteomics
  Neurobiology
  
• 出版者：Springer Wien
• ISSN：1438-2199

文摘

The metabolic roles of mitochondria go far beyond serving exclusively as the major producer of ATP in tissues and cells. Evidence has shown that mitochondria may function as a key regulator of skeletal muscle fiber types and overall well-being. Maintaining skeletal muscle mitochondrial content and function is important for sustaining health throughout the lifespan. Of great importance, β-hydroxy-β-methylbutyrate (HMB, a metabolite of l-leucine) has been proposed to enhance the protein deposition and efficiency of mitochondrial biogenesis in skeletal muscle, as well as muscle strength in both exercise and clinical settings. Specifically, dietary supplementation with HMB increases the gene expression of peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α), which represents an upstream inducer of genes of mitochondrial metabolism, coordinates the expression of both nuclear- and mitochondrion-encoded genes in mitochondrial biogenesis. Additionally, PGC-1α plays a key role in the transformation of skeletal muscle fiber type, leading to a shift toward type I muscle fibers that are rich in mitochondria and have a high capacity for oxidative metabolism. As a nitrogen-free metabolite, HMB holds great promise to improve skeletal muscle mass and function, as well as whole-body health and well-being of animals and humans. Keywords β-Hydroxy-β-methylbutyrate Mitochondrial biogenesis Fiber-type transformation Skeletal muscle health