ALIMENTAZIONE E INTEGRAZIONE POST WORKOUT copia

!
INTEGRATORI!E!ALIMENTAZIONE!
POST!WORKOUT!!
Antonio!Paoli!!
Dipar&mento,di,Scienze,Biomediche,
ALCUNI,CONCETTI…,
COSA,ACCADE,DOPO,L’ALLENAMENTO?,
D.W.D. West et al. / The International Journal of Biochemistry & Cell Biology 42 (2010) 1371–1375
eration, connective tissue and fat infiltration, calcium dysr
and muscle weakness among other effects.
Metabolismo,proteico,muscolare,,
esercizio,fisico,e,nutrizione,Am,J,Physiol,1997,
14,
16,
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14,
12,
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12,
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10,
8,
*!
*!
10,
8,
6,
6,
4,
4,
2,
2,
0,
0,
rest,
3h,
Sintesi,
24h,
48h,
Catabolismo,
Regime!ipocalorico!
rest,
3h,
Sintesi,
24h,
48h,
Catabolismo,
Regime!normocalorico!
ESISTE,LA,FINESTRA,ANABOLICA?,
The,&ming,of,protein,intake,for,recovery,ea&ng,and,at,
other,meals,in,the,day,(a,20–25g,serve,is,the,maximal,
need),is,more,important,than,the,total,daily,protein,
consump&on.,,
,
Bangsbo((at(al.(Scand(J(Med(Sci(Sports(2010:(20((Suppl.(2):(ii–iv((
Nutrient?driven(increases(in(MPS(are(of(finite(duraCon((~1.5(h);(switching?off(thereaJer(
despite(sustained(amino(acid(availability(and(intramuscular(anabolic(signaling.(
Intriguingly,(this(“muscle?full(set?point”(is(delayed(by(resistance(exercise((RE)((i.e.(the(
feeding×exercise(combinaCon(is(‘more(anabolic’(than(nutriCon(alone)(even(≥24(h(beyond(
a(single(exercise?bout;(casCng(doubt(on(the(importance(of(nutrient(Cming(vs.(sufficiency(
per(se.((
P.J.,Atherton,and,K.,Smith,,
The!Biomedical!Basis!of!Elite!Performance,
The!Queen!Elizabeth!II!Conference!Centre,!London,!UK,
19L21!March!2012,
•  I,due,principali,determinan&,della,proteostasi,del,muscolo,
scheletrico,sono,l’a_vità,fisica,e,la,disponibilità,di,nutrien&,
•  L’effebo,anabolico,della,nutrizione,è,correlata,principalmente,
dal,trasporto,e,dall’incorporazione,degli,aminoacidi,deriva&,dalle,
fon&,proteiche,alimentari,nel,muscolo,scheletrico,
•  Lo,scopo,dell’incorporazione,è,di,compensare,la,perdita,di,
proteine,muscolari,che,vengono,perse,,nei,periodi,di,
“digiuno”,(postabsorp&ve),dovu&,ad,esempio,all’ossidazione,di,
AA,o,alla,cessione,dello,scheletro,carbonioso,per,la,
gluconeogenesi,(Wackerhage,&,Rennie,,2006),
E’,l’equilibrio,dinamico,(in,condizioni,di,salute,e,mobilità,–,BED,
REST???),tra,ciclo,‘fastedjloss/fedjgain’,,,nella,proteostasi,che,
garan&sce,la,costanza,della,massa,muscolare.,
,
Ma,quali,sono,le,“componen&,anaboliche”,della,nutrizione?,
,
•  Primo,lavoro,su,effebo,anabolico,di,un,pasto,misto,abribuiva,
effebo,esclusivamente,ad,EAA,(Smith,et,al.,1992),
•  Il,gruppo,di,Atherton,(Cuthbertson,et,al.,2005),ha,dimostrato,
l’effebo,dose,dipendente,e,l’effebo,di,sturazione,di,10,g,di,EAA,
equivalen&,a,20,g,di,proteine,(Moore,et,al,2009),
TIME,COURSE,DELLA,SUPPLEMENTAZIONE,DI,PROTEINE,
1h,30’,
30’,
( 3jfold),,
2,h,
Atherton,et(al.(2010,,
Based(on(developmental(concept(introduced(by(Joe(
Millward(wherein(muscle(protein(accreCon(is(physically(
limited(by(the(inelasCc(collagen(connecCve(Cssue(of(the(
endomysium(surrounding(each(fibre((the(‘bag?full’(
hypothesis)(Millward(et(al.(1994).((
(
It,is,at,this,point,the,muscle,becomes,
refractory(to,s&mula&on,despite,
sustained,eleva&ons,of,Aas,.,,
,
‘musclejfull’,phenomenon,(Bohe,et(al.(
2001;,Atherton,et(al.(2010,,
,
INSULINA,
•  Proteine,da,sole,causano,!,insulina,simile,a,pasto,misto,
(Atherton,et,al.,2010),
•  Insulina,sembra,non,contribuire,,all’effebo,anabolico,di,EAA,su,
MPS,
EAA,infusates,robustly,s&mulate,MPS,even,when,insulin,is,‘clamped’,at,
postabsorp&ve,concentra&ons,(5,μIU,ml−1,with,the,βjcell,inhibitor,octreo&de;,
Greenhaff,et(al.(2008).,,
,
•  Che,ruolo,Insulina?,
•  Riduzione,del,40j50%,proteolisi,
a,rise,in,insulin,to,just,15,μ,IU,ml−1,(3×,postabsorp&ve,concentra&ons),is,
sufficient,to,mimic,the,50%,inhibi&on,of,MPB,(NB,the,maximal,effect,size),
caused,by,a,mixed,meal,(Wilkes,et(al.(2009).,,
,
se in insulin
centrations)
f MPB (NB
meal (Wilkes
ffect cannot
ns (18 g h−1
stabsorptive
2008). Thus,
sponses via
se regulates
es. It follows
hat in MPB,
ent induced
o resistance
upon both
ysiological Society
exercise there is a latent period (prior to rises in MPS)
of a duration which seems to relate to the magnitude
Figure 1. The ‘muscle-full’ effect. Relationship between MPS,
AA and intramuscular signalling
Atherton,&,Smith,J,Physiol,2012,
molecular and cellular events that occur in skeletal
muscle in response to a single bout of exercise is
essential to understand how nutritional interventions
might modulate these responses and promote (or
inhibit) subsequent training adaptations. When such
a view on training is taken, it becomes clear that any
chronic training-induced adaptation is merely the
in muscle, together with the accompanying mechanical stress (particularly muscle damage caused by
physical contact and/or eccentric work), activate
several key kinases and phosphatases involved in
signal transduction. Chief among these are the
50 -adenosine
monophosphate-activated
protein
kinases (AMPK), several of the mitogen-activated
Figure 1. Schematic representation of the time-course of selected contraction-induced physiological, biochemical, and molecular responses
in skeletal muscle that lead to the training adaptation. Adapted and redrawn from Hood (2001).
Hawley,et,al,J,Sport,Sci,2006,
Upstream Regulatory Elements"
Exercise Stimuli
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"Nutrition
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" Enviroment "
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" Psychology"
Training mod."
D
O
W
N
S
T
R
E
A
M!
Physiological system "Cardiovascular
"Endocrine
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"Organs"
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"Tissues"
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"Receptors"
Cells and Cell Signaling"
Gene interactions Expression"
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" Immune, etc"
Stimoli per la crescita della massa
muscolare"
L’aumento della massa muscolare non è un effetto di
un’unica causa specifica, ma il prodotto della
sommazione di diversi adattamenti a differenti
stimoli specifici."
"
"
Non esiste un solo metodo per sviluppare ipertrofia
ma occorrono molteplici modalità di stimolazione
con effetti diversi"
Acute,increases,in,MPS,axer,exercise,in,the,absence,of,EAA,
nutri&on,provide,a,more,prolonged,rise,in,MPB,such,that,the,
net,effect,is,nega&ve,muscle,protein,balance,(Biolo,et(al.(
1995).,,
,
If,such,EAA,deficiency,persisted,throughout,training,,this,
would,lead,to,maladapta&on;,you,can’t,build,or,remodel,
muscle,without,amino,acids!,,
,
It,follows,that,increasing,dietary,EAA,availability,axer,exercise,
enhances,both,the,magnitude,and,dura&on,of,the,increase,in,
MPS,(Pennings,et(al.(2011).,,
,
,
Following,exercise,in,the,fasted,state,,the,rates,of,both,protein,
synthesis,and,breakdown,are,increased,but,,compared,with,
res&ng,condi&ons,,the,net,(nega&ve),balance,is,abenuated,
because,the,increase,in,protein,synthesis,is,greater,than,the,
increase,in,protein,breakdown,(Biolo,,Maggi,,Williams,,Tipton,,&,
Wolfe,,1995;,Phillips,,Tipton,,Aarsland,,Wolf,,&,Wolfe,,1997).,,
,
Inges&ng,a,mixture,of,carbohydrate,and,amino,acids,before,or,
immedij,ately,axer,comple&on,of,a,training,session,(Tipton,et,al.,,
2001),counteracts,this,catabolic,state,by,increasing,amino,acid,
availability,and,transport,into,muscle,(Biolo,,Tipton,,Klein,,&,
Wolfe,,1997).,In,this,situa&on,,protein,synthesis,is,increased,
(Biolo,et,al.,,1997;,Borsheim,,Tipton,,Wolf,,&,Wolfe,,2002),,while,
the,increase,in,protein,breakdown,is,abenuated,(Biolo,et,al.,,
1997),resul&ng,in,a,net,posi&ve,protein,balance.,,
,
,
,
Recently,,Karlsson,et,al.,(2004),,examined,the,effect,of,resistance,
exercise,alone,or,in,combina&on,with,oral,intake,of,branchjchain,
amino,acids,(BCAA),on,the,signalling,pathways,responsible,for,
transla&onal,control,of,protein,synthesis.,In,that,study,,a,single,
bout,of,resistance,training,led,to,a,robust,and,persistent,(2,–,3,h),
increase,in,p70S6k,phosphoryla&on,that,was,further,enhanced,by,
BCAA,inges&on.,These,workers,speculated,that,BCAA,
supplementa&on,enhances,protein,synthesis,during,recovery,from,
resistance,training,through,a,p70S6kj,dependent,signalling,cascade,
(Karlsson,et,al.,,2004).,,
,
•  Dopo,RT,CHO,+,PRO,maggiore,sint,proteica,e,più,a,lungo,che,
solo,CHO,(isoenerge&co),(Borsheim,,Aarsland,,&,Wolfe,,2004),
ma,da&,più,recen&,invece,suggeriscono,che,non,ci,sia,
differenza,(Staples,et,al,2011),
,
•  Meglio,immediatamente,dopo,T,(Tipton,et,al,2001),anche,se,
alcuni,autori,suggeriscono,che,sia,irrilevante,(basta,che,sia,
nelle,24h),
,
•  Dose,minima,6,g,,max,20,g,in,più,assunzioni,giornaliere,
PROTEIN TURNOVER, EXERCISE, INTAKE, AND SEX DIFFERENC
Fig. 2. Resistance training induces
which likely sensitizes the muscle
time should result in a greater MP
Fig. 1. A: changes in muscle protein synthesis (MPS) and muscle protein
breakdown (MPB) in response to feeding (i.e., amino acids). B: changes in
MPS and MPB in response to resistance exercise and feeding. Chronic
application of these anabolic stimuli, as in B, results in muscle hypertrophy.
Burd,et,al,J,Appl,Physiol,,2009.,,
fasted
state is currently unknown but likely involves one or all
of the major proteolytic pathways (calpains, caspases, lysomes,
Phillips SM, unpublished
anabolic opportunity” may
resistance exercise; howeve
offer some additional advan
stimulated to the greatest ex
the effect of feeding there
the protein source (i.e., a
quantity, the timing of poste
of carbohydrate to stimulat
feeding, MPS may also be i
and/or training overload (i
68, 75, 107). A valid que
short-term changes we obs
long-term chronic change
Some evidence exists to
studies short-term changes
tatively predictive of long
•  Abituale,consumo,di,proteine,influenza,metabolismo,proteico,
muscolare,
•  Harber,et,al,(2005),",MPS,basal,aumentata,dopo,7,giorni,di,
dieta,iperproteica,(35%,Kcal,tot).,–,Da,considerare,però,bilancio,
tra,MPS,e,MPB,
•  Abituale,consumo,proteico,riduce,risposta,sintesi,proteica,a,
esercizio?(Volpi,et,al,2001),
Presumably,(the(increased(protein(synthesis(was(mediated(by(increased(signalling(
of(the(translaCon(iniCaCon(pathways.(However,(increased(muscle(protein(synthesis(
occurred(without(increased(phos?(phorylaCon(of(two(proteins(downstream(of(mTOR(
(ribosomal(protein(S6(and(eIF4G).(This(finding(suggests(that(muscle(protein(
synthesis(is(enhanced(by(high(protein(intake,(but(may(not(be(associated(with(a(
chronic(alteraCon(in(components(of(the(mTOR(signalling(pathway((
(
tile intensity and whether it interplays with feeding is not understood.
This was investigated following two distinct resistance exercise (RE)
contraction intensities using an intrasubject design in the fasted (n !
10) and fed (n ! 10) states. RE consisted of 10 sets of knee
extensions. One leg worked against light load (LL) at 16% of
one-repetition maximum (1RM), the other leg against heavy load
(HL) at 70% 1RM, with intensities equalized for total lifted load.
Males were infused with [13C]leucine, and vastus lateralis biopsies
were obtained bilaterally at rest as well as 0.5, 3, and 5.5 h after RE.
Western blots were run on muscle lysates and phosphospecific antibodies used to detect phosphorylationAmstatus
of targets involved in
J Physiol Endocrinol Metab 298: E257–E269, 2010.
First
published
November
10,
2009; doi:10.1152/ajpendo.00609.2009.
regulation of FSR. The intramuscular collagen
FSR was evenly
increased following LL- and HL-RE and was not affected by feeding.
Myofibrillar
FSR wasaffect
unaffected
by LL-RE,
whereas HL-RE
resulted
Contraction intensity
and feeding
collagen
and myofibrillar
protein
a delayed in
improvement
(0.14 muscle
" 0.02%/h, P # 0.05). Myofibrillar
synthesis rates in
differently
human skeletal
FSR was increased at rest by feeding (P # 0.05) and remained
1
3
3
in the
postexercise
compared
the
fasting
Lars Holm,elevated
Gerrit van late
Hall,2 Adam
J. Rose,
Benjamin F.period
Miller,1 Simon
Doessing,1with
Erik A.
Richter,
1
and Michaelcondition.
Kjaer
The Rp-s6k-4E-binding protein-1 (BP1) and the mitogenInstitute of Sports Medicine, Bispebjerg Hospital and Center of Healthy Aging, Department of Biomedical Sciences, Faculty
activated
protein
kinase
(MAPk)
activated
by the HL
of Health Sciences,
and Section
of Human
Physiology,
Department pathways
of Exercise and were
Sport Sciences,
University
of Copenhagen,
Copenhagen,and
Denmark
intensity
were suggested to be responsible for regulating myofiSubmitted 2 October
2009; accepted
final form
3 November 2009
brillar
FSR in in
response
to adequate contractile activity. Feeding
predominantly affected Rp-s6k and eukaryotic elongation factor 2
Holm L, van Hall G, Rose AJ, Miller BF, Doessing S, Richter EA, have been shown to exert divergent effects on muscle protein
Kjaer M. Contraction intensity
and feeding affect collagen andin
myofibrillar
phosphorylations
correspondence
with rates
the (95,
observed
changes
in
turnover and synthesis
101). However,
except from
protein synthesis rates differently in human skeletal muscle. Am J Physiol differences in exercise intensity, decisive differences in conmyofibrillar
FSR,November
whereas
4E-BP1
remained to respond only to the
Endocrinol Metab 298: E257–E269,
2010. First published
10, traction
type and exercise volume characterize various kinds of
2009; doi:10.1152/ajpendo.00609.2009.—Exercise stimulates muscle
exercises;
differences
the response
because of
HL contraction intensity. Thus
the thus,
study
designin allows
usmay
to be
conclude
protein fractional synthesis rate (FSR), but the importance of contracseveral
varying
and
uncontrolled
parameters.
Therefore,
the
tile intensity and whether itthat
interplays
feeding is not
understood.
thewithMAPkand
mammalian
target
of rapamycin-dependent
sigisolated
effect
of
contraction
intensity
cannot
be
extracted
from
This was investigated following two distinct resistance exercise (RE)
studies, nor
can it be elongation
done from a comparison
the
naling
responds
activity,
whereas
mainly of
was
contraction intensities using
an intrasubject
design in to
the contractile
fasted (n ! these
10) and fed (n ! 10) states. RE consisted of 10 sets of knee number of studies investigating just one exercise type (9, 17,
found to respond to feeding. Furthermore, although functionally
extensions. One leg worked against light load (LL) at 16% of 27, 36, 70, 78, 80, 89). The present insight of how contraction
one-repetition maximum (1RM),
the other
leg against heavyand
load the
intensity
alone affects
the muscle
protein synthesis
rates is to
linked,
the contractile
supportive
matrix
structures
upregulate
(HL) at 70% 1RM, with intensities equalized for total lifted load. our knowledge based on few studies. In 2005, Atherton et al.
protein
synthesis
rate quite
differently
in response
to feeding
andat
Males were infused with [their
C]leucine,
and vastus
lateralis biopsies
(3) stimulated
the extensor
digitorum longus
muscle in rats
were obtained bilaterally atcontractile
rest as well as 0.5,
3, and 5.5 hand
after RE.
two frequencies, designed to mimic endurance- or resistanceactivity
intensity.
Western blots were run on muscle lysates and phosphospecific anti-
isolated effect of con
these studies, nor c
number of studies in
27, 36, 70, 78, 80, 8
intensity alone affec
Il,problema,è,la,complessità,delle,vie,coinvolte.,
our knowledge base
Sembra,che,l’alimentazione,agisca,su,alcune,vie,mentre,il,RT,su,
(3) stimulated the ex
two frequencies, des
altre,
type exercises. Desp
cluded that only afte
fibrillar protein synt
changes in mTOR-r
tein-1 (BP1) and euk
(3). Recently, Kuma
various contraction
fected myofibrillar p
sities at !60% onesubjects induced sig
concern though in
enhanced protein sy
shown elsewhere (7
presumably was cau
therefore might be s
synthesis rate at the
from the low exerci
Along with the m
cellular matrix and th
structure in the skele
type exercises. Despite unmatched exercise volume, they conbodies used to detect phosphorylation status of targets involved in
cluded that only after the resistance-type stimulation the myocollagen matrix for s
regulation of FSR. The intramuscular
collagen FSR was evenly
gas chromatography-combustion-isotope
ratio
mass
spectrometry;
fibrillar
protein
synthesis
rate
was
increased
with
concomitant
increased following LL- and HL-RE and was not affected by feeding.
the severe functiona
in mTOR-ribosomal
s6 kinase-binding proprotein
turnover;
molecular
signaling;
exercise; protein
nutrition
Myofibrillar FSR was unaffected
by LL-RE,
whereas HL-RE
resulted changes
tein-1
(BP1)
and
eukaryotic
elongation
factor
(eEF)2
signaling
in a delayed improvement (0.14 " 0.02%/h, P # 0.05). Myofibrillar
gen structures are p
FSR was increased at rest by feeding (P # 0.05) and remained (3). Recently, Kumar et al. (61) investigated how a range of
elevated late in the postexercise period compared with the fasting various contraction intensities in young and old humans afproteins increase the
1
2
3
Downloaded from http://ajpendo.physiology.org/ at Norges Idre
13
Mechanical Activation of mTOR Signaling
that confers insulin-induced
ansfected with FLAG-tagged
pamycin-resistant kinase-dead
ere preincubated with 50 nM
with 100 nM insulin. (A and
anti-FLAG resin followed by
2481 phosphorylated mTOR
s an autophosphorylation site
ivity.77 (C and D) Whole cell
KB [P-PKB(473)], or (D) phosmonstrate that RR-mTOR can
rom the inhibitory actions of
ctivity.
Figure 2. Schematic of the mechanisms involved in the regulation of
mTOR signaling by growth factors, amino acids and mechanical
stimuli. Growth factors, nutrients and mechanical stimuli activate
signaling to p70S6k and growth through an mTOR-dependent
pathway. Growth factors and nutrients activate mTOR signaling
through a wortmannin-sensitive mechanism, whereas mechanical
stimuli activate mTOR signaling through a wortmannin-independent
mechanism. The wortmainnin-independent mechanism employed by
mechanical stimuli involves a phospholipase D (PLD)-dependent
increase in phosphatidic acid (PA) which then binds to mTOR in the
FRB domain and activates mTOR signaling.
Hornberger,et,al,Cell,Cycle,5:13,,1391j1396,,1,July,2006,,
S6k
S6k
D.W.D. West et al. / The International Journal of Biochemistry & Cell Biology 42 (2010) 1371–1375
1373
Fig. 1. Cellular events contributing to muscle protein synthesis, protein accretion and hypertrophy. Dashed arrows with solid heads on left hand side depict broad hypothesized
patterns of force transmission. Tracings of IGF-1 and the satellite cell pathways rely primarily on animal data.
the myofibrils to the extracellular matrix). The costamere and
2008b) muscle following a period of unloading, or increased activathe myotendinous junction each permit the transmission of force
tion of FAK following increased muscle loading (Fluck et al., 1999).
D.W.D. West et al. / The International Journal of Biochemistry & Cell Biology 42 (2010) 1371–1375
from the force-generating myofibrillar apparatus to the extracelThus, in response to mechanical stress, integrins may serve as a
lular matrix and the mechanical deformation of transmembrane
regulatory node for the coordinated up-regulation of the synthesis
receptors (integrins) at these sites produce conformational changes
and incorporation of muscle proteins into the functional myofibre
eration,
connective tissue and fat infiltration, calcium dysr
in many of the receptor-associated multimodular proteins (Jani
(Fig. 3).
and Schock, 2009). In particular, mechanically induced conforma- and muscle weakness among other effects.
tional changes of focal adhesion kinase (FAK) proteins can elicit a
2.5. Proxy markers of hypertrophy
S6K