Leading Edge
Review Integrative Biology of Exerci
John A.Hawley,1,2,*Mark Hargreaves,3Michael J.Joyner,4and Juleen R.Zierath5,6,*
1Exerci&Nutrition Rearch Group,School of Exerci Sciences,Australian Catholic University,Fitzroy,Victoria3065,Australia
2Rearch Institute for Sport and Exerci Sciences,Liverpool John Moores University,Meryside L35UA,UK
3Department of Physiology,The University of Melbourne,Parkville,Victoria3010,Australia
4Department of Anesthesiology,Mayo Clinic,Rochester,MN55905,USA
5Department of Molecular Medicine,Karolinska Institutet,von Eulers va¨g4a,17177Stockholm,Sweden
6The Novo Nordisk Foundation Center for Basic Metabolic Rearch,Faculty of Health and Medical Sciences,University of Copenhagen, 2200Copenhagen,Denmark
*Correspondence:john.hawley@acu.edu.au(J.A.H.),juleen.zierath@ki.(J.R.Z.)
dx.doi/10.ll.2014.10.029
Exerci reprents a major challenge to whole-body homeostasis provoking widespread pertur-bations in numerous cells,tissues,and organs that are caud by or are a respon to the incread metabolic activity of contracting skeletal muscles.To meet this challenge,multiple integrated and often redundant respons operate to blunt the homeostatic threats generated by exerci-induced increas in muscle energy and oxygen demand.The application of molecular techniques to exerci biology has provided greater understanding of the multiplicity and complexity of cellular networks involved in exerci respons,and recent discoveries offer perspectives on the mech-anisms by which muscle‘‘communicates’’with other organs and mediates the beneficial effects of exerci on health and performance.
Introduction
苹果手机连上wifi却上不了网怎么办Superior locomotive ability was once esntial for human survival and a fundamental reason that Homo sapiens evolved and prospered.Physical activity was obligatory for evading predators and food procurement.Evolutionary theory describes the mechanism of natural lection as‘‘survival of th
勇敢的心电影efittest,’’the underlying supposition being that the‘‘fit,’’as oppod to the ‘‘unfit,’’had a greater likelihood of survival.Modern day humans run faster,jump higher,and are stronger than at any time in his-tory.Yet exerci,particularly when undertaken to an individ-ual’s maximum,is a complex process involving the synchronized and integrated activation of multiple tissues and organs at the cellular and systemic level.Though the reductionist approach of discting biological systems into their constituent parts has been valuable in explaining the basis of many biochemical pro-cess,for exerci biologists,this approach has vere limita-tions:the integrative biology of exerci is extremely complex and can be neither explained nor predicted by studying the indi-vidual components of various entities.
Exerci reprents a major challenge to whole-body homeo-stasis,and in an attempt to meet this challenge,myriad acute and adaptive respons take place at the cellular and systemic levels that function to minimize the widespread disruptions. Previous reviews have considered the metabolic respons to exerci and the cellular mechanisms that underpin skeletal muscle adaptation to exerci training(Basl-Duby and Olson, 2006;Coffey and Hawley2007;Egan and Zierath,2013;Hop-peler et al.,2011).Here,we highlight that voluntary,dynamic, whole-body exerci provokes widespread changes in numerous cells,tissues,and organs that are caud by or are a res
pon to the incread metabolic activity of contracting skeletal muscle.To meet this challenge,multiple integrated and redundant respons operate to blunt the homeostatic threats generated by the incread energy and O2demand.In this‘‘muscle-centric’’view of exerci,the systemic(cardiovas-cular,respiratory,neural,and hormonal)respons are viewed as‘‘rvice functions,’’supplying the contracting muscles with fuel and O2to sustain a given level of activity.The fundamental premi is that multiscale and redundant respons simulta-neously operate to blunt the many challenges to whole-body ho-meostasis caud by the demands of the contracting muscles. The application of molecular biology techniques to exerci biology has provided a better understanding of the multiplicity and complexity of cellular pathways involved in the exerci respons.Recent discoveries offer perspectives on the role played by skeletal muscle in numerous homeostatic process and on the mechanisms by which muscle‘‘communicates’’with other organs such as adipo tissue,liver,pancreas, bone,and brain.
Why Study Exerci?
There are veral broad reasons to study exerci.Hypothes generated over the last two decades from comparative physiol-ogists(Hochachka et al.,1999)and anthropologists(Bramble and Lieberman,2004)suggest that the combined traits of supe-rior endurance capacity and an impressive
ability to thermoreg-ulate permitted ancestral humans from the high plains of East Africa to succeed as game hunters and thereby obtain high-pro-tein sources of food that were esntial for the emergence of larger brains and complex cooperative behavior.Human skeletal muscles,limbs,and the supporting ventilatory,cardiovascular, and metabolic systems were well suited for upright
locomotion,
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with economy of movement for bipedal walking and running far exceeding that of other primates(Bramble and Lieberman, 2004;Brooks,2012).At this time,lifestyle and energy availability were inextricably linked to the periodic cycles of feasts and famines,with certain genes evolving to regulate efficient storage and utilization of endogenous fuel stores,the so-called‘‘thrifty genes’’(Neel,1962).Expanding on Neel’s original concept,sur-vival during feast-famine cycles throughout the hunter-gatherer period was accompanied by the lection of genes and traits to supp档案室工作总结
ort a‘‘physical activity cycle’’(Booth et al.,2002;Chak-ravarthy and Booth,2004),and under the constraints most of the prent human genome evolved.During modern times, tho alleles and traits that evolved for energy storage and locomotion are now expod to an inactive lifestyle and access to energy-den foods over an extended lifespan,thereby increasing the risk of chronic dia.Therefore,thefirst reason to study exerci is to provide insight into the pathogenic pro-cess underpinning the numerous contemporary physical inactivity-mediated disorders.
The recent emergence of noncommunicable dias as ma-jor killers in industrialized nations(Bauer et al.,2014)and the role of physical activity in preventing and/or treating the conditions is a cond reason to study exerci.A dentary life is now so prevalent that it has become common to refer to exerci as hav-ing‘‘healthy benefits’’even though the exerci-trained state is the biologically normal condition.It is a lack of exerci that is abnormal and carries health risks(Booth and Lees,2006).Phys-ical inactivity increas the incidence of at least17unhealthy conditions and related chronic dias(Booth et al.,2000), whereas a low exerci capacity is an independent predictor of all-cau mortality(Blair et al.,1996;Myers et al.,2002)and morbidity(Willis et al.,2012).Yet exerci in both biological rearch and as primary preventative therapy continues to be undervalued and underutilized by the scientific and medical communities.Conquently,a third re
ason to study exerci is to determine the preci mechanisms by which it promotes whole-body health and to establish molecular links between specific exerci interventions and dia prevention.Although the last decade has en major advances in unraveling the mechanism(s)by which cellular,molecular,and biochemical pathways are affected by exerci,the understanding of how the effects are linked to health benefits is still lacking.In this context,epidemiological evidence suggests that only half of the protective effects of exerci can be explained on the basis of traditional risk factors like reductions in blood pressure(BP) and blood lipids(Joyner and Green,2009).
A fourth reason to study exerci is to understand the capacity of various mammalian species to function in extreme environ-ments and to test hypothes about physiological regulation under such conditions.In this context,humans are competent athletes,but our capacity for locomotion is paltry compared with that of other species that are more powerful and faster and posss greater endurance.With respect to speed,the cheetah(Acinonyx jubatus)reigns supreme among terrestrial mammals,achieving maximum velocities of113km/hr(Sharp, 1997),making the world’s fastest human(with a top speed of 48km/hr)em rather pedestrian.The pronghorn antelope(Anti-locapra Americana)can sustain speeds of>80km/hr for4–5km,and the Greyhound and sled dog are similarly
capable of extraor-dinary bursts of speed(Poole and Erickson,2011).Notwith-standing such comparisons,rearch into the‘‘limits’’of athletic capacity provides insight into the roles of various organ systems involved in maximizing human performance(Joyner and Coyle, 2008).Such enquiry is not new.In1925,Nobel Laureate A.V. Hill published a paper on the physiological basis of athletic re-cords(Hill,1925)and was thefirst to describe the concept of an individual’s maximum oxygen uptake(VO2max)as an index of the highest energy demand that can be met aerobically while exercising.Hill propod that an individual’s VO2max was the sin-gle best measure of cardio-respiratory performance and could be ud for quantifying the adaptation of many organ systems to physical activity or inactivity(Bastt,2002).Perhapsfittingly, the test for VO2max for the asssment of athletic potential orig-inally propod by Hill is now recognized as a better predictor of mortality than any other established risk factor or biomarker for cardiovascular dia(Myers et al.,2002).Clearly the biology underlying maximal exerci performance confers advantages beyond the athletic arena!
黎明使者锐雯Voluntary Exerci:More Than Muscle Contraction
What We Mean When We Talk about Exerci
Exerci is the voluntary activation of skeletal muscle for recre-ational,sporting,or occupational activities.The distinction be-tween voluntary,whole-body in vivo respons to exerci versus tho evoked by other experimental models is important. Ex vivo electrical stimulation of an isolated skeletal muscle,for instance,evokes an action potential and‘‘contraction’’and trig-gers intracellular pathways with putative roles in training adapta-tion(Fitts and Holloszy,1978).However,whole-body,voluntary exerci induces a range of additional physiological respons that are critical for muscle performance(and movement). Accordingly,many effects obrved in animals and isolated sys-tems frequently differ from tho en in humans in vivo,and care should be taken when extrapolating respons from one t of conditions or a given experimental model to another (Schlegel and Stainier,2007).
Voluntary exerci encompass many elements beyond simple muscle contraction.Volitional effort generated in the mo-tor cortex of the brain drives the spinal cord to recruit motor units,resulting in specific movement patterns.In parallel with neural signals to skeletal muscle,there are also powerful neural feedforward signals to the cardiovascular,respiratory,and metabolic and hormonal systems,along with neural feedback from the contracting skeletal muscles,that generally permit metabolic demands to be met with limited disruption of homeo-stasis(Figure1).
Numerous issues relating to the speed,force,duration,and in-tensity of muscle contractions,along with the total muscle mass engaged in the activity,are important for a complete understand-ing of the physiological respons to exerci.An isometric or static contraction of high force but short duration compress blood vesls in the contracting musculature and limits blood flow and O2delivery to tho muscles while simultaneously increasing BP.In contrast,during sustained rhythmic exerci like cycling or running,the contraction times are short,there is little disruption of muscle bloodflow,and perturbations in BP Cell159,November6,2014ª2014Elvier Inc.739
are minimized.The muscle mass engaged in exerci is critical,as it determines both the absolute O 2flux and total fuel require-ments.For most aerobic-bad activities,such as running or cycling,active muscle mass amounts to 15kg in a 70kg athlete (Coyle et al.,1991),although for rowing and cross-country skiing (for which the athlete is substantially taller and heavier),this is markedly higher (Hagerman 1984).The nomenclature relating to the quantification of exerci intensity is also relevant becau the prevailing work rate exerts a major role in determining the overall physiological respons to exerci.For exerci lasting >5min,intensity is typically expresd as a percentage of an in-dividual’s VO 2max .Low-,moderate-,and high-intensity exerci correspond to <45%,45%–75%,and >75%of individual VO 2max ,respectively.
Skeletal Muscle Energy Metabolism
佩雷尔曼ATP is required to fuel the cellular process supporting muscle contraction.The include the maintenance of sarcolemmal excitability (Na +/K +ATPa),reuptake of Ca 2+into the sarco-plasmic reticulum (Ca 2+ATPa),and force generation via actin-myosin cross-bridge cycling (myosin ATPa).Intramus-cular [ATP]is remarkably well maintained over a wide range of exerci intensities and durations,and while [ATP]declines under certain exerci and/or environmental conditions,the magnitude of change is small when considered against the total turnover of ATP within active myocytes.During sprint exerci,ATP turnover can increa 100-fold above rest (Gaitanos et al.,1993;Parolin et al.,1999),a range of metabolic activity exceeding that in all other tissues and one that pos a major energetic challenge to the contracting myofibers.Given that intramuscular [ATP]is relatively small,metabolic pathways responsible for ATP resynthesis are rapidly activated.During short-term ( 30–60s)maximal exerci,this is achieved primar-ily through substrate-level phosphorylation via the breakdown of creatine phosphate and during the conversion of gluco units,derived almost entirely from intramuscular glycogen,to lactate (Gaitanos et al.,1993;Parolin et al.,1999).The mobilization of extramuscular substrates is also critical to maintain skeletal muscle metabolism during prolonged exerci (van Loon et al.,2005;Wasrman,2009).Thus,the liver increas the
relea
Figure 1.The Physiological Respons to Voluntary,Dynamic Exerci
Multiple organ systems are affected by exerci,initiating diver homeostatic respons.
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of gluco into the circulation (initially derived from glycogenolysis and later from gluconeogenesis),and the adipo-cyte increas the hydrolysis of its triglyc-eride stores and the relea of long-chain nonesterified fatty acids into the blood-stream.
The relative contribution of carbohy-drate and lipid to oxidative metabolism is determined primarily by the prevailing exerci intensity (Romijn et al.,1993)and is influenced by prior diet,training status,x,and environmental condi-tions (Jeukendrup 2003).The contribution from the oxidation of carbohydrate-bad fuels ris with increasing exerci inten-sity,with a concomitant reduction in lipid oxidation.Converly,during prolonged exerci at a fixed level of moderate intensity,rates of carbohydrate oxidation decline as lipolysis and fat oxidation increa.The regulation of fuel mobilization and utiliza-tion involves a combination of local factors such as sarcoplasmic [Ca 2+],intramuscular levels of ATP breakdown products (ADP,AMP,IMP,Pi),and muscle temperature and intramuscular sub-strate availability,as well as systemic factors such as the plasma level of key hormones (epinephrine,insulin,and glucagon)and circulating metabolites (Hawley et al.,2006).The factors are not only involved in mediating the acute respon to exerci,but also activate signaling pathways critical for many of the chronic adaptations to regular exerci training.Recent reviews have summarized the various cellular and molecular factors involved in the regulation of skeletal mu
scle carbohydrate (Jen-n and Richter,2012;Richter and Hargreaves,2013)and lipid (Jeppen and Kiens,2012)metabolism during exerci,as well as the interactions between them (Spriet,2014).Oxygen Transport System
At rest,whole-body O 2consumption in healthy,young,adult humans averages about 3.5ml/kg/min,with 20%–25%of this ud by resting skeletal muscle.Thus,for a 70kg person,resting O 2consumption is 250ml/min,with 50ml/min taken up by skeletal muscle.In lean,healthy,untrained adults,VO 2max is typically 10–15times resting values.In elite endurance-trained athletes,VO 2max values can exceed 85ml/kg/min (Saltin and A
˚strand,1967).Though O 2fluxes in humans are high,they are marginal compared to values achieved by elite racehors with VO 2max values of 110l/min,equating to 220ml/kg/min (Poole and Erickson,2011).
VO 2max is determined by the combined capacities of the cen-tral nervous system to recruit motor units,the pulmonary and cardiovascular systems to deliver O 2to contracting skeletal muscles,and the ability of tho muscles to consume O 2in the oxidative,metabolic pathways.Associated with large increas in O 2consumption during maximal exerci in humans are peak values for cardiac output (Q)and ventilation of 40and 200l/min,
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reprenting 8-and 20-fold increas,respectively,above rest.In addition,blood flow to active skeletal muscle can increa 100times above basal levels,accounting for up to 80%–90%of Q.Notably,there is only a modest ( 20%)increa in mean arterial blood pressure (MAP),whereas values for arterial PO 2,PCO 2,and pH remain esntially identical to rest until maximal exerci intensities are reached.
The cardiovascular adjustments to exerci require an intact autonomic nervous system and are driven by three signals:(1)feedforward ‘‘central command’’related to motor output,which activate lected areas in the brainstem cardiovascular (and res-piratory)centers to stimulate increas in heart rate (HR),BP,and ventilation;(2)afferent feedback from thinly myelinated and unmyelinated type III and IV afferents in contracting muscles that increa sympathetic activation;and (3)baroreceptors in the carotid sinus and aortic arch that provide feedback on BP to the brainstem cardiovascular centers.The HR respon to ex-erci is driven primarily by central command-mediated vagal withdrawal and activation of sympathetic outflow to the heart.Both factors also augment cardiac stroke volume,and the action of the so-called ‘‘muscle pump’’ensures that venous return from the active muscle vasculature maintains diastolic filling and stroke volume (SV).The central motor drive
and central com-mand are subject to ‘‘fine-tuning’’via feedback signals that monitor substrate levels,MAP,blood gas and pH,fluid status,and body temperature despite the marked ho-meostatic challenges associated with high-intensity exerci (Figure 2).
The primary mechanism responsible for skeletal muscle hy-peremia during exerci is vasodilation in the active skeletal muscle,most notably in the small arterioles.Mechanical,neu-ral,and humoral factors,including tho relead from con-tracting skeletal muscle,have been implicated in this respon.Becau the ri in muscle blood flow is cloly coupled to metabolic rate,vasodilating signal(s)relead from contracting skeletal muscles roughly in proportion to their O 2demand is(are)responsible (Hellsten et al.,2012).Candidate dilator sub-stances and mechanisms include inward rectifying K +chan-nels,adenosine,ATP from various sources,products of skeletal muscle metabolism,and reactive O 2species.However,no sin-gle substance can fully account for the increas in muscle blood flow,and the molecular identity of one or more of the signals is unknown.
Blood flow is redistributed away from the kidney,liver,other visceral organs,and inactive muscle via vasoconstriction in the vascular beds,condary to incread sympathetic activ-ity during exerci.This permits a higher fraction of Q to be deliv-ered to active skeletal muscle and partially off
ts the fall in total peripheral resistance as a result of skeletal muscle vasodilation.Blood flow to the central nervous system remains either un-changed or increas slightly,and coronary blood flow in-creas.Becau evaporation of sweat is the major mechanism for dissipation of heat during exerci,especially at higher envi-ronmental temperatures,there is an increa in skin blood flow
and sweating-induced fluid loss with exerci (Gonza
´lez-Alonso et al.,2008).With incread exerci intensity,the skin becomes a target for vasoconstriction as skeletal muscle blood flow in-creas despite incread metabolic heat production.To main-tain MAP,skeletal muscle takes priority over skin blood flow.As exerci approaches VO 2max ,the finite cardiac pumping capac-ity means that active skeletal muscle is also subject to vasocon-striction (Calbet et al.,2004).With incread environmental stress,the combination of progressive hyperthermia and dehy-dration further challenges the cardiovascular system during pro-longed,strenuous exerci (Gonza
´lez-Alonso et al.,2008).The critical functions of the pulmonary system are to maintain arterial oxygenation and to facilitate the removal of CO 2produced during oxidative metabolism.This is achieved by incread ventilation in proportion to exerci intensity,and arte-rial PO 2and PCO 2are
generally maintained at resting levels until heavy exerci.The factors responsible for the marked increa in ventilation include descending central command in parallel with motor cortical activation of skeletal muscle that stimulates the brainstem respiratory centers and feedback stimulation from type III and IV afferents (Dempy et al.,2014).In most healthy individuals exercising at a level,arterial oxyhemo-globin saturation (SaO 2)is well maintained.However,in some highly trained endurance athletes,high-intensity exerci results in a significant drop in SaO 2that impairs O 2delivery to contract-ing skeletal muscle and results in impaired exerci capacity (Amann et al.,2006).Another threat to locomotor muscle O 2de-livery and performance during high-intensity exerci is
reflex
Figure 2.Complex and Redundant Physio-logical Control Mechanisms during Volun-tary,Dynamic Exerci
怀旧的唯美句子Motor cortical drive leads to skeletal muscle contraction,as well as parallel activation (‘‘central command’’)of key neuro-endocrine respons,fuel mobilization,and support systems that in-crea oxygen and substrate delivery to con-tracting skeletal muscle.The integrated respon is fine-tuned by afferent feedback,involving me-chano-and chemo-nsitive type III and IV affer-ents in active skeletal muscle,but also by critical nsors that monitor various parameters,including mean arterial blood pressure (MAP),blood gluco concentration,oxygen and carbon dioxide levels,body temperature,and blood volume.
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sympathetic vasoconstriction of the limb skeletal muscle vascu-lature,condary to activation of type III and IV afferents in respiratory muscles(Dempy et al.,2002).Increas in respira-tory muscle work during heavy exerci result in incread metabolite accumulation and activation of the afferents.This reflex rves to direct a greater proportion of the limited Q to the respiratory muscles b
ut at the expen of the locomotor muscles and exerci performance.
The acute cardiovascular adaptations to both dynamic and isometric exerci lead to patterns of long-term remodeling and adaptations that increa VO2max and minimize disruptions in whole-body homeostasis.The autonomic and nsory feed-back systems described previously are subject to chronic ret-ting so that,during dynamic exerci,somewhat lower BPs are tolerated,thus permitting greater increas in skeletal muscle bloodflow.This is accompanied by cellular changes in the brain-stem cardiovascular center that tend to be pro-vagal and sym-pathoinhibitory.The changes partly explain why exerci at any given submaximal work rate after training is accompanied by a lower HR and BP.They also contribute to the chronic BP lowering effects of exerci in general.Adaptations to resistance training are less well characterized.However,during maximal weight lifting,BP can exceed480/350mmHg(MacDougall et al.,1985),consistent with the idea that compression of the blood vesls in the contracting skeletal muscles evokes re-spons designed to overcome‘‘under perfusion’’by substan-tially increasing BP.
With dynamic exerci,there is considerable remodeling of the vascular system,especially in the skeletal muscles subjected to training,including an increa in the diameter of large con-ducting vesls like the femoral artery for leg exerci(Green et al.,2012).There is also an increa in the nu
mber of arterioles and incread capillary density in the trained musculature.This structural remodeling is driven by a complex and redundant quence of events that includes NO,prostaglandins,and vascular endothelial growth factor(VEGF)signaling pathways (Hoier and Hellsten,2014).The time cour of remodeling also varies by blood vesl size.Early in exerci training,there is a marked increa in nitric oxide syntha(NOS)expression in the large conducting vesls in respon to incread shear stress.However,as the caliber of the vesl increas with training,the shear stress normalizes and NOS expression returns to baline values.Though many of the adaptations are restricted to the vascular beds of the working muscle,improved endothelial function appears to be a whole-body respon to exerci training.
Dynamic exerci training is associated with an increa in cardiac chamber size,but not wall thickness,that facilitates the increa in SV caud by this mode of training.Endurance training promotes volume hypertrophy,whereas resistance training does not cau major changes in the thickness of cardiac muscle.The stimulus for cardiac volume hypertrophy with dynamic exerci training is stretch of the ventricle caud by the incread venous return from the periphery.This stretch is facilitated by training-induced increas in blood volume and catecholamine concentrations.The cellular mechanisms responsible for cardiac hypertrophy with exerci training in
volve activation of a number of pathways,including the insu-lin-like growth factor1(IGF-1)-phosphatidylinositide3-kina (PI3K)-Akt/protein kina B axis(Ellison et al.,2012),in particular PI3K(p110a).Downstream of Akt,exerci-induced cardiomyo-cyte hypertrophy and proliferation appears to be associated with reduced C/EBP b expression and a concomitant increa in CITED4expression(Bostro¨m et al.,2010).Cardiac hypertrophy also involves de novo cardiomyocyte formation by activation of both circulating and tissue-specific cardiac progenitor cells.
In highly motivated young,healthy individuals,VO2max does not appear to be limited by muscle mitochondrial oxidative capacity(Boushel et al.,2011).Rather,O2delivery to skeletal muscle is rate limiting,and although this is determined by both convective and diffusive mechanisms,central cardiovascular function and the ability to increa active skeletal muscle blood flow appear to be critical(Gonza´lez-Alonso and Calbet,2003). However,muscle mitochondrial oxidative capacity does appear to be an important determinant of endurance exerci perfor-mance(Joyner and Coyle,2008).Thus,treadmill running time at submaximal exerci intensity is ud as a physiological correlate of transgenic interventions that impact muscle oxida-tive capacity(Potthoff et al.,2007;Wang et al.,2004). Skeletal Muscle Matters
Skeletal Muscle Fiber Type and Adaptation Plasticity The application of surgical techniques to exerci
biochemistry in the1960s(Bergstro¨m and Hultman1966)made it possible to obtain small(100–150mg)samples of human skeletal muscle for histological and biochemical studies to identify specific morphological,contractile,and metabolic properties.Using the approaches,differentfiber types have been identified along with their contractile characteristics,and the have been related to functional and metabolic properties of skeletal muscle during exerci(Saltin et al.,1977).The metabolic poten-tial of muscle has also been evaluated by determining different substrate and enzyme activities.Comprehensive discussion of skeletal musclefiber types and the gene programs responsible forfiber-specific properties are beyond the scope of this Review and have been summarized elwhere(Basl-Duby and Olson 2006;Saltin et al.,1977;Schiaffino and Reggiani1996;Zierath and Hawley2004).However,a brief overview of the classification of human musclefiber types and their metabolic potential is warranted.
Histologically,skeletal muscle appears uniform but is comprid of myofibers that are heterogeneous with respect to size,metabolism,and contractile function.On the basis of spe-cific myosin heavy-chain isoform expression,myofibers can be classified into type I,type IIa,type IId/x,and type IIbfibers, with types I and IIa exhibiting high oxidative potential and capil-lary supply and with types IIx and IIbfiber being primarily glyco-lytic(Pette and Staron2000;Saltin et al.,1977;Schiaffino and Reggiani1996).Typ
e I myofibers are typically referred to as ‘‘slow-twitchfibers’’becau they exert slow contraction time to peak tension,owing to the ATPa activity associated with the type I myosin,whereas type IIfibers are termed‘fast-twitch’myofibers and have quicker contraction time but a rapid fatigue profile(Basl-Duby and Olson2006;Saltin et al.,1977).With endurance training,the enhancement of the oxidative potential of type IIx and IIbfibers is markedly incread,resulting in a
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