REVIEW
Ae obic Exe cise in he Managemen o Me abolic
Dys unc ion Associa ed Fa y Li e Disease
Ma iana Ve delho Machado
1,2
1
Se iço de Gas en e ologia, Hospi al de
Vila F anca de Xi a, Vila F anca de Xi a,
Po ugal;
2
Faculdade de Medicina,
Uni e sidade de Lisboa, Lisboa, Po ugal
Abs ac : Seden a ism is he pandemic o mode n imes. I is associa ed wi h se e al
medical condi ions including obesi y, ype 2 diabe es melli us, ca dio ascula diseases and
also li e disease, pa icula ly me abolic dys unc ion associa ed a y li e disease (MAFLD).
In an e a when MAFLD is he mos p e alen ch onic li e disease wo ldwide, whils no
pha macological he apy has been app o ed o i , exe cise has p o ed o be e ec i e in
imp o ing li e s ea osis. In e es ingly, exe cise dec eases li e a e en in he absence o
weigh loss. The challenge o he clinician is o mo i a e he obese pa ien wi h MAFLD,
and associa ed co-mo bidi ies, who has c ys allized a seden a y beha io , a imes when
e e y need is a he dis ance o a click on he In e ne , and he en i e wo ld can be isi ed
behind a sc een. In his e iew, he agg ega e e idence on he mechanisms and e ec s o
exe cise in he managemen o MAFLD is summa ized, wi h simple ecommenda ions o
e e yday clinical p ac ice.
Keywo ds: me abolic dys unc ion-associa ed a y li e disease, physical ac i i y, ae obic
exe cise
In oduc ion
Seden a ism and unheal hy die ing a e he pandemic beha io s o he XXI cen u y.
1
A ound 85% o he US popula ion achie e less han wha is p econized by he
Wo ld Heal h O ganiza ion o daily physical ac i i y o heal h.
2
Up o one hi d o
he wo ld’s popula ion is physically inac i e, which is s ongly associa ed wi h
obesi y, ype 2 diabe es melli us, ca dio ascula diseases and o e all mo ali y.
3–5
Physical inac i i y is also associa ed wi h me abolic dys unc ion-associa ed a y
li e disease (MAFLD), independen ly o body weigh .
6
MAFLD e e s o he ec opic accumula ion o a in he hepa ocy es, which can
be explained by me abolic dys unc ion associa ed wi h adiposopa hy. Adiposopa hy
is he consequence o an ene gy o e load in he adipose issue, usually in o e -
weigh /obese pa ien s. An o e whelmed adipose issue can also a ise in subjec s
wi h no mal body mass index, in which he pe sonal a h eshold, ha is he
amoun o a he indi idual adipose issue can handle, is su passed.
7
The sick
adipose issue eleases a ha accumula es ec opically in he li e , bu also in he
ca dio ascula sys em, and p omo es sys emic in lamma ion, insulin esis ance, and
he me abolic synd ome. The a y li e u he enhances insulin esis ance and
de angemen s in lipid me abolism, ensuing in a loop o me abolic dys unc ion.
8
Recen ly, an in e na ional panel o expe s p oposed he ollowing diagnos ic
c i e ia o MAFLD:
9
p esence o hepa ic s ea osis in pa ien s wi h ype 2 diabe es
Co espondence: Ma iana Ve delho
Machado
Faculdade de Medicina, Uni e sidade de
Lisboa, A enida P o esso Egas Moniz,
Lisboa, 1649-035, Po ugal
Tel +35 1912620306
Email m e [email p o ec ed]
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy 2021:14 3627–3645 3627
© 2021 Machado. This wo k is published and licensed by Do e Medical P ess Limi ed. The ull e ms o his license a e a ailable a h ps://www.do ep ess.com/ e ms.php
and inco po a e he C ea i e Commons A ibu ion – Non Comme cial (unpo ed, 3.0) License (h p://c ea i ecommons.o g/licenses/by-nc/3.0/). By accessing he wo k
you he eby accep he Te ms. Non-comme cial uses o he wo k a e pe mi ed wi hou any u he pe mission om Do e Medical P ess Limi ed, p o ided he wo k is p ope ly a ibu ed. Fo
pe mission o comme cial use o his wo k, please see pa ag aphs 4.2 and 5 o ou Te ms (h ps://www.do ep ess.com/ e ms.php).
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy Do ep ess
open access o scien i ic and medical esea ch
Open Access Full Tex A icle
Recei ed: 25 May 2021
Accep ed: 29 July 2021
Published: 11 Augus 2021
Diabe es, Me abolic Synd ome and Obesi y downloaded om h ps://www.do ep ess.com/
Fo pe sonal use only.
melli us and/o who a e o e weigh /obese. In lean non-
diabe ic pa ien s, i equi es e idence o hepa ic s ea osis
and he p esence o a leas 2 o he ollowing me abolic
abno mali ies: (1) Wais ci cum e ence (WC) ≥ 102 and
88 cm in Caucasian men and women, espec i ely (o ≥ 90
and 80 cm in Asian men and women, espec i ely); (2)
Blood p essu e ≥ 130/85 mmHg o speci ic d ug ea men ;
(3) Plasma iglyce ides ≥ 150 mg/dL o speci ic d ug
ea men ; (4) Plasma high-densi y lipop o ein (HDL)-
choles e ol < 40 mg/dL o men and < 50 mg/dL o
women o speci ic d ug ea men ; (5) P ediabe es (ie,
as ing glucose le els 100–125 mg/dL, o 2-h pos -load
glucose le els 140–199 mg/dL o HbA1c 5.7–6.4%); (6)
Homeos asis model assessmen (HOMA) o insulin esis-
ance sco e ≥ 2.5; (7) Plasma high-sensi i i y C- eac i e
p o ein le el > 2 mg/L.
MAFLD,
9
is he li e pandemic o ou imes. I a lic s
up o one ou h o he global popula ion.
10
I is also he
mos apidly inc easing e iology o end-s age li e
disease,
11
being he second leading cause o ch onic li e
disease in pa ien s on wai lis o li e ansplan a ion
o e all, bu al eady he leading cause in women.
12
Impo an ly, MAFLD is no only associa ed wi h an
inc eased li e - ela ed mo ali y bu also associa ed wi h
inc eased all-cause mo ali y.
13
Indeed, e en hough
a ecen me a-analysis could no demons a e an associa-
ion be ween MAFLD and ca dio ascula mo ali y,
13
he
p esence o MAFLD inc eases o e 60% he isk o ha ing
ca dio ascula e en s, which canno be solely explained
by he associa ion be ween MAFLD, obesi y and he me a-
bolic synd ome.
14
Up o now, he e is no app o ed ea men o MAFLD,
and he managemen o hese pa ien s elies on he p omo-
ion o a heal hy li es yle, wi h die and exe cise, aiming
o weigh loss.
15
The de ini ion o seden a ism is no consensual and is
o en ende ed as si ing ime. Con e sely, physical ac i -
i y e e s o any ene gy- equi ing mo emen . Physical
i ness is a se o a ibu es ha e lec ole ance o physical
ac i i y and can be measu ed by speci ic es s. Exe cise
e e s o planned physical ac i i y ha is s uc u ed and
epe i i e, wi h a speci ic in ensi y, equency and
du a ion.
16
The in ensi y o exe cise can be g aded acco d-
ing o he me abolic equi alen asks (METs) spen . One
MET e e s o he amoun o oxygen consumed while
si ing a es , and co esponds o 3.5 mL o oxygen
pe kg o body weigh pe minu e. One MET is equi alen
o 1 kcal pe kg o body weigh pe hou .
17
Fo example,
walking a a speed o 4.8 kms pe hou is equi alen o 3
METs, while jogging a a speed o 6.4 o 8 kms pe hou is
equi alen o 7 METs. Exe cise is conside ed ligh when i
spends 1.1–3.9 METs; mode a e 4–6 METs and igo ous/
in ense o mo e han 6 METs. Ano he way o ep esen i
is acco ding o he VO
2
max, ha is, he maximum capa-
ci y o oxygen u iliza ion exp essed as L/min.
18
Exe cise is
conside ed mode a e when equi es 40–60% o VO
2
, and
igo ous when i equi es a leas 60%.
The e a e 3 di e en ypes o exe cise: ae obic, esis-
ance and lexibili y. Ae obic o endu ance exe cise is
hy hmic, can be main ained con inuously and elies on
la ge muscle g oups. Resis ance o s eng hening exe cise
exe s muscle o e load equi ing anae obic me abolism.
Las ly, lexibili y o s e ching exe cise aims o inc ease
he join ange o mo ion and muscle ex ensibili y.
19
In his e iew, we will c i ically summa ize he e i-
dence o he e ec o exe cise on he managemen o
MAFLD, wi h pa icula emphasis on ae obic exe cise.
Wha is he Role o Physical Ac i i y
in he De elopmen and
P og ession o MAFLD?
Epidemiological s udies displayed an in e se co ela ion
be ween physical ac i i y and he p e alence o MAFLD,
independen ly o he way physical ac i i y was assessed:
ecalls, dia ies, ques ionnai es o mo ion senso s/accele -
ome e s, as shown in Table 1.
In a c oss-sec ion Ko ean s udy wi h 3718 pa icipan s,
physical ac i i y e alua ed h ough s uc u ed ques ion-
nai es showed an in e se associa ion wi h he isk o
ha ing MAFLD, which was independen o isce al adi-
pose issue. Indeed, being on he highes qua ile o phy-
sical ac i i y dec eased by almos one hi d he isk o
ha ing MAFLD
20
and o hal he isk o de eloping de
no o MAFLD.
21
A la ge coho o 42,661 pa icipan s
om he Ne he lands showed simila associa ions.
22
E en lowe le els o physical ac i i y han he ecom-
mended ( ha is a leas 150 minu es pe week) con e ed
bene i o e being en i ely inac i e.
22
Fu he mo e,
pa ien s wi h insulin esis ance/ ype 2 diabe es melli us
and elde ly bene i ed he mos .
22
The associa ion be ween physical ac i i y, assessed by
ques ionnai es, and MAFLD was co obo a ed by se e al
s udies in di e en popula ions: Eu opean,
23
Is aeli,
24
Asian
Indians,
25
Chinese,
26
and Ko ean.
27
The agg ega e s udies
sugges ed a dose– esponse associa ion.
26
Fu he mo e, he
h ps://doi.o g/10.2147/DMSO.S304357
Do eP ess
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy 2021:14
3628
Machado Do ep ess
Powe ed by TCPDF (www. cpd .o g)
Table 1 Obse a ional S udies E alua ing he E ec o Physical Ac i i y on MAFLD
Re e ence Coun y S udy
Design
N E alua ion o
Physical Ac i i y
Diagnosis o
MAFLD
Main Resul s
Pe seghin G,
2007
23
I aly C oss-
sec ional,
Coho
191 Ques ionnai e
1
H-MRS ● In e se co ela ion be ween hepa ic a con en
and PA.
● ↓ p e alence o MAFLD acco ding o qua ile o
PA: 25 > 11 < 25 >2%
Zelbe -Sagi
S, 2008
24
Is ael C oss-
sec ional,
Coho
349 Sel - epo ed PA in
he las yea
Abdominal US ● The MAFLD g oup engaged in less ae obic o
esis ance PA
Kis le KD,
2011
42
USA C oss-
sec ional,
Coho
813
MAFLD
pa ien s
Sel - epo ed PA
ques ionnai e om
he NHANES
Li e biopsy ● Mode a e-in ensi y PA did no associa e wi h
s ea ohepa i is o ib osis s age
● Vigo ous PA ↓ isk o s ea ohepa i is: OR 0.65
[0.43–0.98]
● Doubling ecommended ime spen in igo ous
PA ↓ isk o ad anced ib osis: OR 0.53 [0.29–0.97]
Ge be L,
2012
32
USA C oss-
sec ional,
Coho
3056 Ac i i y coun s om
accele ome e
eadings o 7 days
FLI >60 ● Pa ien s wi h MAFLD spen less ime pa icipa ing
in ac i i y a any le el
● A e age PA was 28.7 coun s/minu e/day lowe in
MAFLD pa ien s han con ols
Bae JC,
2012
37
Ko ea C oss-
sec ional,
Coho
72359 Sel - epo ed
ques ionnai es
Abdominal US ● Subjec s who exe cised >3x/week, ≥30 min/
session, o 3 consecu i e mon hs p esen ed lowe
isk o MAFLD: OR 0.53–0.72
Miyake T,
2015
38
Japan C oss-
sec ional,
Coho
6370 Ques ionnai e Abdominal US ● Pe iodical exe cise ↓ isk o ha ing MAFLD: OR
0.707 [0.546–0.914]
Kwak MS,
2015
20
Ko ea C oss-
sec ional,
Coho
3718 PA ques ionnai e
om he NHANES
Abdominal US ● PA was in e sely associa ed wi h MAFLD:
● 4 h s 1s qua ile: OR 0.68 [0.54–0.85]
● 3 d s 1s qua ile: OR 0.74 [0.59–0.93]
Ryu S, 2015
6
Ko ea C oss-
sec ional,
Coho
139056 In e na ional PA
Ques ionnai e Sho
Fo m (Ko ean
e sion)
Abdominal US ● P e alence o MAFLD ↓ in physically ac i e s
inac i e:
● Minimally ac i e g oup: OR 0.94 [0.02–0.95]
● HEPA g oup: OR 0.8 [0.78–0.82]
● P e alence o MAFLD ↑ wi h inc easing si ing
ime:
● 5–9 hou s/day: OR 1.04 [1.02–1.07]
● ≥ 10 hou s/day: OR 1.09 [1.06–1.11]
Hallswo h
K, 2015
33
UK C oss-
sec ional,
Case-
con ol
37
MAFLD,
37
con ols
Seden a y beha iou ,
PA and E expendi u e
we e assessed by
a mul isenso a ay
o e 7 days
1
H-MRS ● MAFLD pa ien s compa ed o con ols:
● Spen an hou ex a pe day being seden a y
● Walked 18% ewe s eps
● ↓ ac i e E expendi u e by 40%
● ↓ o al E expendi u e by 8%
Tsunoda K,
2016
43
Japan P ospec i e
coho , FU
4.2 yea s
1149 Ques ionnai e MAFLD: by US;
s ea ohepa i is
by ↑ ALT o
AST
● Vigo ous PA p e en ed p og ession o
s ea ohepa i is: OR 0.55 [0.32–0.94]
● Mode a e o low in ensi y PA p esen ed no
associa ion wi h p og ession o s ea ohepa i is
(Con inued)
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy 2021:14 h ps://doi.o g/10.2147/DMSO.S304357
Do eP ess
3629
Do ep ess Machado
Powe ed by TCPDF (www. cpd .o g)Powe ed by TCPDF (www. cpd .o g)
Table 1 (Con inued).
Re e ence Coun y S udy
Design
N E alua ion o
Physical Ac i i y
Diagnosis o
MAFLD
Main Resul s
Sung KC,
2016
40
Ko ea P ospec i e
coho , FU
4.95 yea s
169347 In e na ional PA
Ques ionnai e Sho
Fo m (Ko ean
e sion)
Abdominal US ● ≥5x/week exe cise s no exe cise:
● ↓ isk o inciden s ea osis: OR 0.86 [0.80–0.92]
● ↑ likelihood o s ea osis esolu ion: OR 1.40
[1.25–1.55]
Wei H,
2016
28
China C oss-
sec ional,
Coho
2054
male
Sel - epo ed
ques ionnai e
FLI ≥60 ● Dose-dependen ↑ p e alence o MAFLD ac oss
he e iles o si ing ime.
● Si ing ime >7.1 hou s/day associa ed wi h ↑
p e alence o MAFLD (OR 1.09 [1.04–1.67])
Kea ing SE,
2016
34
Aus alia C oss-
sec ional,
Coho
82 Ac i i y coun s om
accele ome e
eadings o 4 days
1
H-MRS ● No associa ions be ween PA and seden a y
beha io and he p e alence o MAFLD
Kwak MS,
2017
21
Ko ea P ospec i e
coho , FU
4.2 yea s
1373 PA ques ionnai e
om he NHANES
Inciden
MAFLD by US
● To al and leisu e PA was in e sely associa ed wi h
inciden MAFLD
● ↓ PA a FU associa ed wi h ↑ inciden MAFLD: 4 h
qua ile s 1s qua ile o ↓ PA OR 1.45 [1.04–2.02]
Byambasukh
O, 2019
22
Ne he lands C oss-
sec ional,
Coho
42661 Sel epo ed
ques ionnai e o
e alua e HEPA
FLI ≥60 ● Highe mode a e/ igo ous PA was dose-
dependen ly associa ed wi h ↓ isk o MAFLD: OR
o PA quin iles: 0.78 [0.71–0.86] > 0.64 [0.58–0.70]
> 0.53 [0.48–0.59] > 0.51 [0.46–0.56]
● E en PA lowe han ecommenda ions was be e
han inac i i y
● Occupa ional PA o e s no clea heal h bene i s
Li YF, 2019
26
China C oss-
sec ional,
Case-
con ol
543
MAFLD,
543
con ols
In e na ional PA
Ques ionnai e Sho
Fo m (Chinese
e sion)
Abdominal US ● Bo h mode a e (OR 0.62 [0.41–0.92]) o igo ous
(OR 0.60 [0.40–0.91]) in ensi y PA associa ed wi h
↓ isk o MAFLD in men, independen ly o seden a y
ime o E expendi u e
Jang DK,
2019
27
Ko ea C oss-
sec ional,
Case-
con ol
32391 Sel epo ed
ques ionnai e o
e alua e HEPA
Hepa ic
s ea osis index
● PA nega i ely associa ed wi h MAFLD (mos s
leas ac i e: OR 0.7 [0.6–0.8]) and lean MAFLD (OR
0.5 [0.4–0.7])
Ge age AM,
2019
41
B azil P ospec i e
coho , FU
2.5 yea s
5860 In e na ional PA
Ques ionnai e
Abdominal US ● Lowe likelihood o imp o ing s ea osis in
subjec s who emained inac i e (OR 0.64) o
became inac i e (OR 0.66)
● Lowe isk o acqui ing MAFLD in subjec s who
emained ac i e (OR 0.75) o became ac i e (OR 0.75)
Bha SP,
2019
25
India C oss-
sec ional,
Case-
con ol
342 Ques ionnai e Abdominal US ● Mean PA was lowe in cases han con ols (33.3
±3.6 s 36.2±0.5 MET/min)
● To al E expendi u e was lowe in cases han
con ols (2707.6±505.6 s 2904.3±690.3 kcal)
C oci I,
2019
29
Aus alia C oss-
sec ional,
Coho
15781 Sel - epo ed
ques ionnai e
FLI ≥60 ● Fo each addi ional 1 hou /day o seden a y
beha io , he isk o ha ing MAFLD ↑ 4% [3–6]
● High ca dio espi a o y i ness a enua ed he
nega i e ole o seden a y beha io up o 7 hou s/
day on MAFLD.
(Con inued)
h ps://doi.o g/10.2147/DMSO.S304357
Do eP ess
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy 2021:14
3630
Machado Do ep ess
Powe ed by TCPDF (www. cpd .o g)Powe ed by TCPDF (www. cpd .o g)
p o ec i e e ec o physical ac i i y was equally s ong in
pa ien s wi h lean MAFLD.
27
A c oss-sec ional s udy on 139,056 Ko ean, who
unde wen a comp ehensi e annual o biennial heal h
examina ion, showed ha spending mo e han 5 hou s
si ing pe day inc eased he isk o ha ing ul asonog a-
phy-diagnosed MAFLD.
6
O he s udies in Asian and
Aus alian popula ions con i med a dose– esponse associa-
ion be ween si ing ime and he p e alence o
MAFLD.
28–30
Indeed, spending mo e han 7 hou s si ing
pe day inc eased by 10% he isk o MAFLD, indepen-
den ly o body mass index (BMI), insulin esis ance and
dyslipidemia.
28
The de imen al e ec o spending mo e
han 10 hou s si ing pe day pe sis ed e en in hose who
we e o he wise physically ac i e.
6
These esul s poin ou
o he di e ence be ween inac i i y and absence o exe -
cise. Indeed, a small s udy on 19 o e weigh o obese
adul s showed ha dec easing si ing ime h ough 2 min-
u es bou s o ligh o mode a e in ensi y walking was
e ec i e in dec easing insulin esis ance.
31
O he s udies used a mo e objec i e way o quan i y
physical ac i i y, such as accele ome e s. Indeed, a s udy
wi h 3056 pa icipan s om he Na ional Heal h and
Nu i ion Examina ion Su ey (NHANES) e alua ed he
physical ac i i y du ing 7 consecu i e days h ough accel-
e ome e eadings. When he accele ome e eco ded less
han 100 coun s pe minu e pe day, he pa ien was con-
side ed seden a y. MAFLD was diagnosed when a y li e
index (FLI) was highe han 60 and in he absence o o he
ch onic li e diseases. In his s udy, pa ien s wi h MAFLD
spen less ime pa icipa ing in any ac i i y, and p esen ed
an a e age o a ound less han 30 coun s/min/day as com-
pa ed o con ols.
32
Simila ly, a small s udy om
Newcas le, UK, e alua ed 7-days physical ac i i y and
ene gy expendi u e using a mul isenso y a ay on 37
pa ien s wi h MAFLD and 1000 heal hy con ols.
MAFLD pa ien s spen an ex a hou being seden a y,
walked up o one- i h ewe s eps and expended 40%
less ene gy being ac i e.
33
A small s udy om Aus alia
ailed o co obo a e his associa ion,
34
when hepa ic s ea-
osis was measu ed by magne ic esonance spec ome-
y (MRS).
Impo an ly, no all physical ac i i ies seem o equally
p omo e heal h. Indeed, i is leisu e o ec ea ional, and no
occupa ional, physical ac i i y ha seems o induce he
mos bene i s in heal h. Rec ea ional physical ac i i y
usually induces he con ac ion o la ge muscle g oups
while inc easing whole-body me abolism and ca diac ou -
pu . Du ing ec ea ional physical ac i i y one can es
when a igued. Occupa ional physical ac i i y mo e e-
quen ly in ol es hea y li ing, p olonged s anding, and
highly epe i i e mo emen s.
35
Epidemiologic s udies sug-
ges an in e se, dose– esponse associa ion be ween he
isk o hype ension and ec ea ional, bu no occupa ional,
physical ac i i y.
35
Fu he mo e, ec ea ional physical
ac i i y is associa ed nega i ely, whe eas occupa ional
posi i ely, wi h BMI, cen al obesi y and insulin
esis ance.
36
Simila ly, la ge-popula ion s udies ha e
shown ha ec ea ional, bu no occupa ional, physical
ac i i y seems o be p o ec i e agains ha ing MAFLD.
22
Rega ding he p ac ice o exe cise, a la ge popula ion
Ko ean s udy also showed ha subjec s ha p ac iced
exe cise a leas 3 imes pe week, o a leas 30 minu es
each ime o mo e han 3 mon hs, dec eased up o hal he
isk o ha ing MAFLD.
37
A c oss-sec ional s udy om
a subsample o 375 pa icipan s in he Is aeli Na ional
Heal h And Nu i ion Su ey showed ha engaging in
any kind o spo s dec eased one- hi d he isk o ha ing
Table 1 (Con inued).
Re e ence Coun y S udy
Design
N E alua ion o
Physical Ac i i y
Diagnosis o
MAFLD
Main Resul s
Joo JH,
2020
30
Ko ea C oss-
sec ional,
Coho
13518 In e na ional PA
Ques ionnai e
(Ko ean e sion)
Hepa ic
s ea osis index
● The o s o ha ing MAFLD inc eased ac oss
qua iles o si ing hou s: 1.07 [0.88–1.31] < 1.16
[1.06–1.41] < 1.34 [1.11–1.61]
Kim D,
2021
52
USA P ospec i e
coho , FU
10.6 yea s
5207
MAFLD
pa ien s
PA ques ionnai e Abdominal US ● ↑ du a ion o PA in e sely associa ed wi h all-
cause mo ali y (highe s lowe qua ile: OR 0.46
[0.28–0.75]) and ca dio ascula mo ali y (OR 0.28
[0.008–0.98]) in pa ien s wi h MAFLD
Abb e ia ions: E, ene gy; FLI, Fa y Li e Index; HEPA, heal h-enhancing physically ac i e; NHANES, Na ional Heal h and Nu i ion Examina ion Su ey; PA, physical
ac i i y; US, ul asound.
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy 2021:14 h ps://doi.o g/10.2147/DMSO.S304357
Do eP ess
3631
Do ep ess Machado
Powe ed by TCPDF (www. cpd .o g)Powe ed by TCPDF (www. cpd .o g)

MAFLD, pe each s anda d de ia ion inc ease in he phy-
sical ac i i y sco e. These associa ions we e s onge o
esis ance exe cise as compa ed o ae obic exe cise, which
was explained by p obable misclassi ica ion o sel -
epo ed physical ac i i y.
24
Simila esul s we e shown
on a la ge Japanese coho .
38
Fu he mo e, engagemen
in egula exe cise also seems o be associa ed wi h p o-
ec ion om inciden MAFLD, imp o emen and emis-
sion o MAFLD.
39–41
Those e ec s p esen ed a dose–
esponse pa e n and occu ed o any amoun o
exe cise.
40
Engaging in physical ac i i y no only seems o con e
p o ec ion om ha ing MAFLD, bu i is also associa ed
wi h less se e e disease, in a dose-dependen manne . Two
la ge-popula ion s udies om he US and Japan showed
ha engaging in igo ous, bu no mode a e, physical
ac i i y dec eased he chances o p og ession o s ea ohe-
pa i is and li e ib osis.
42,43
The au ho s hypo hesized ha
igo ous physical ac i i y consumes la ge amoun s o ATP,
which ac i a es AMP kinase, elici ing inc eased ATP p o-
duc ion h ough a y acids oxida ion and glucose
anspo .
44
Fu he mo e, igo ous physical ac i i y can
lead o deple ion o hepa ic glycogen, igge ing a
consump ion.
43
Ano he way o e alua e he ole o physical ac i i y on
he de elopmen o MAFLD is h ough physical i ness,
ansla ing he abili y o he subjec o engage physical
ac i i y. Physically i subjec s, assessed using maximal
eadmill exe cise es o cycle e gome e da a, seem less
suscep ible o ha ing MAFLD, s ea ohepa i is, and se e e
li e ib osis, independen ly o BMI.
45–50
A ecen s udy ollowed 125,264 pa icipan s om he
Nu ses' Heal h S udy and he Heal h P o essionals Follow
up S udy, o up o 25 yea s. I showed ha highe physical
ac i i y also p edic ed a lowe isk o li e - ela ed mo al-
i y, ac oss all he ange o BMI. Physical ac i i y could
e en ab oga e he excessi e li e - ela ed mo ali y
obse ed wi h obesi y. Indeed, walking a leas 3 hou s
pe week could ha e p e en ed 25% o li e - ela ed
dea hs.
51
Fu he mo e, engaging in physical ac i i y
seems o ha e a p o ound impac on he su i al o
pa ien s wi h MAFLD. A s udy ha e alua ed 5207 pa i-
cipan s om he NHANES ollowed hem o 10 yea s,
assessing physical ac i i y by accele ome e eadings. The
du a ion spen on physical ac i i y was in e sely asso-
cia ed wi h all-cause mo ali y. Subjec s wi h he highes
qua ile o physical ac i i y p esen ed a mo e han hal
dec eased isk o all-cause mo ali y compa ed o he
lowes qua ile o physical ac i i y. The e ec was e en
s onge o ca dio ascula mo ali y.
52
A di e en
Aus alian coho ha also ollowed MAFLD pa ien s
o e a 10-yea pe iod and showed ha low ca dio espi a-
o y i ness was associa ed wi h a 50% inc ease in all-
cause mo ali y.
29
Physiopa hology o Exe cise and
MAFLD
MAFLD occu s when he e is an imbalance be ween a
up ake and iglyce ides p oduc ion in he li e , and hepa-
ic a oxida ion. Mos o he a up ake in o he li e
de i es om he adipose issue, pa icula ly isce al adi-
pose issue. Insulin esis ance p omo es he elease o a
om he adipose issue ha can each he li e , and also,
inc eases hepa ic lipogenesis. In he li e , lipo oxici y can
induce cell s ess, h ough di e en mechanisms, such as
oxida i e s ess, ER s ess, impai ed au ophagy and cell
dea h.
8
Me abolic sys emic in lamma ion and gu dysbio a
also seem o play a ole in he de elopmen and p og es-
sion o MAFLD.
53
Physical ac i i y and exe cise can
p o ec agains MAFLD h ough se e al mechanisms, ac -
ing on di e en playe s, such as he adipose issue, he
muscle, di ec ly on he li e and on he gu mic obio a
54
(Figu e 1).
Exe cise can dec ease isce al adiposi y, pa icula ly
ae obic exe cise.
55
The dec ease in isce al adipose issue
dec eases he in lux o ee a y acids in o he li e .
56
I
also dec eases he me abolic-associa ed sys emic in lam-
ma ion while imp o ing he adipokine p o ile (inducing an
inc ease in adiponec in and a dec ease in lep in).
57,58
Exe cise no only dec eases he quan i y o he adipose
issue bu also changes he s uc u e and unc ion o he
adipocy e. The impo ance o he quali a i e changes in
he adipose issue induced by exe cise can be illus a ed by
an in e es ing expe imen in which ecipien seden a y
mice we e ansplan ed wi h adipose issue om ained
dono mice ( olun a y wheel unning o 11 days). The
ecipien mice expe ienced a d ama ic imp o emen in
glucose ole ance.
59
Exe cise dec eases adiposi y by dec easing he size o
he adipocy es and i s lipid con en .
60
This is o ex eme
ele ance since he enla gemen o adipocy es induces
cellula s ess ( o example, oxida i e and ER s ess),
61,62
leading o a dis inc adipokine p o ile, o insulin
esis ance
63
(which inc eases i s lipoly ic capaci y by spil-
ling ou o ee a y acids in o he ci cula ion),
64
and o
h ps://doi.o g/10.2147/DMSO.S304357
Do eP ess
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy 2021:14
3632
Machado Do ep ess
Powe ed by TCPDF (www. cpd .o g)Powe ed by TCPDF (www. cpd .o g)
cell dea h
65
p omo ing adipose issue in lamma ion.
66
Fu he mo e, exe cise induces beijing o he whi e adipose
issue, con e ing a b own-like pheno ype, wi h inc eased
mi ochond ial ac i i y,
59
inc eased uncoupling p o eins
leading o inc eased he mogenesis and inc eased ene gy
expendi u e.
67,68
Exe cise also p o ec s agains MAFLD h ough i s
e ec s on he muscle. Regula exe cise inc eases he muscle
capaci y o oxygen consump ion and oxida i e unc ion, by
inc easing capilla y densi y and inc easing muscle mi o-
chond ial con en and unc ion,
69
o example h ough up e-
gula ion o p o eins in ol ed in mi ochond ial biogenesis,
such as pe oxisome p oli e a o -ac i a ed ecep o gamma
(PPAR-γ) co-ac i a o 1-alpha (PGC1α).
18
The muscle is he main issue o glucose up ake and
s o age.
70
Exe cise and muscle con ac ion p omo e mus-
cle glucose up ake by he ansloca ion o he glucose
ecep o GLUT-4 in o he cellula memb ane, indepen-
den ly o insulin ac ion, and by inc easing muscle insulin
sensi i i y.
71,72
Also, exe cise inc eases he muscle glucose
s o age as glycogen.
73,74
On he o he hand, du ing exe -
cise, he edis ibu ion o blood low om he splanchnic
ci cula ion o he wo king muscles, edi ec s ci cula ing
ee a y acids om he li e in o he muscle.
75
Indeed,
egula exe cise inc eases he up ake and oxida ion o a y
acids by he muscle, as well as he abili y o s o e a y
acids such as in amyocellula iglyce ides.
76
The ela i e
con ibu ion o glucose as uel, compa ed o a , inc eases
wi h wo k a e, bu declines wi h exe cise du a ion.
77
Fu he mo e, in he pos -exe cise pe iod, glucose oxida ion
dec eases a he expense o a oxida ion, in o de o
eplenish glycogen s o age.
78
Las ly, exe cise modula es myokines p oduc ion.
7
Exe cise induces he elease o i isin ha p omo es beijing
o whi e adipose issue, inc easing ene gy expendi u e.
68
I isin also has di ec an i-s ea ogenic e ec s on he li e ,
h ough ac i a ion o PPAR-γ and up egula ion o ib o-
blas g ow h ac o (FGF)-21.
79
On he o he hand, exe -
cise down egula es myos a in,
80
a myokine ha p omo es
adipose issue expansion h ough di ec e ec s on he
adipose issue and h ough down egula ion o i isin.
81,82
Myos a in can also p omo e hepa ic ib ogenesis h ough
di ec ac ion on hepa ic s ella e cells.
83
Mo eo e , exe cise
inc eases ansien ly he syn hesis o in e leukin(IL)-6,
84
Figu e 1 The an i-s ea ogenic mechanisms o exe cise.
Abb e ia ions: VAT, isce al adipose issue; WAT, whi e adipose issue; NEFA’s, non-es e i ied a y acids; ER, endoplasmic e iculum.
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy 2021:14 h ps://doi.o g/10.2147/DMSO.S304357
Do eP ess
3633
Do ep ess Machado
Powe ed by TCPDF (www. cpd .o g)Powe ed by TCPDF (www. cpd .o g)
which induces subsequen inc ease in IL-10, IL-1 ecep o
an agonis and co isol, wi h a ne an i-in lamma o y
e ec .
85
Exe cise has independen an i-s ea ogenic e ec s on
he li e . S udies on animal models showed ha exe cise
dec eases de no o lipogenesis by down egula ing he lipo-
genic ansc ip ion ac o s e ol egula o y-elemen bind-
ing p o ein-1c (SREBP-1c)
86,87
and dec easing he le els
and ac i i y o key enzymes in lipid syn hesis such as
ace yl CoA ca boxylase (ACC) and a y acids syn hase
(FAS).
88
Simul aneously, exe cise inc eases hepa ic mi o-
chond ial a y acids oxida ion, by up egula ing he lipo-
ly ic ansc ip ion ac o PPAR-γ
89
and inc easing he
ac i i y o key enzymes in be a-oxida ion such as be a-
hyd oxyacyl-CoA-dehyd ogenase (β-HAD), ci a e
syn hase and cy och ome c oxidase.
90–92
Exe cise has an an i-oxidan e ec on he li e , which
ansla es in o a dec ease in lipid pe oxida ion, an inc ease
in educed glu a hione con en , and an inc ease in he
ac i i y o an i-oxidan enzymes, such as ca alase, supe -
oxide dismu ase and glu a hione pe oxidase.
93–98
I also
has an an i-in lamma o y e ec , h ough a dec ease in
sys emic in lamma ion media ed by he adipose issue
99
and he muscle,
85
and h ough di ec e ec s on he li e .
Exe cise dec eases he hepa ic umo nec osis ac o -alpha
(TNF-α) and hepa ic esiden mac ophages
in il a ion.
100,101
Fu he mo e, i inhibi s he exp ession
o oll-like ecep o s (TLR) on monocy es and
mac ophages,
102
and inc eases he pool o T egula o y
cells.
103
Physical ac i i y/exe cise modula es o he impo -
an cellula pa hways: i p omo es hepa op o ec i e
au ophagy,
104
and i imp o es mi ochond ial unc ion, p o-
ec ing he mi ochond ia om s uc u al damage.
105–107
Mo eo e , exe cise a enua es mi ochond ial-dependen
hepa ocy e apop osis.
108–110
All hose ac ions a e hepa o-
p o ec i e, wi h he po en ial o dec ease he p og ession
om isola ed s ea osis o s ea ohepa i is and hepa ic ib o-
sis. Animal s udies also sugges ed exe cise o dec ease he
isk o hepa ocellula ca cinoma in s ea o ic li e s.
111–113
Finally, exe cise can modula e he gu mic obio a
owa ds a less s ea ogenic and insulin sensi ize pheno-
ype. Indeed, in humans, exe cise is associa ed wi h an
inc ease in mic obial ichness/di e si y,
114,115
an inc ease
in he ela i e p opo ion o Bac e oide es and
Eu ya chaeo a, whe eas a dec ease in Ac inobac e ia, a
he phylum le el.
116,117
Obesi y and MAFLD a e known o
be associa ed wi h a dec ease in he Bac e oide es/
Fi micu es a io, which is associa ed wi h highe e iciency
in ha es ing ene gy om he die .
53
Fu he mo e, exe cise
helps p ese e he in es inal ba ie , and imp o es bile
acids homeos asis.
118
Ae obic Exe cise and MAFLD
Se e al s udies, mos ly andomized con olled s udies, and
7 me a-analyses e alua ed he e ec o s uc u ed in e -
en ions on ae obic exe cise in MAFLD
119–125
as shown
in Table 2. S udies used di e en exe cise egimens, wi h
di e en in ensi ies, and wi h du a ions anging
121
om 1
week
109
o 1 yea .
126
Mos o hem showed imp o emen s
in hepa ic s ea osis.
54,127,128
A small pe cen age o pub-
lished s udies wi h nega i e esul s mo e o en used less
disc imina i e ools o quan i y li e a , such as CT
scan.
129
The e ec on li e a o exe cise-only in e en ions
anged om a dec ease o 2% up o 50%.
121
Exe cise also
had a modes e ec , dec easing amino ans e ases
le els.
120
Globally, he published s udies ound a signi ican posi-
i e co ela ion be ween changes in BMI and changes in
li e a con en .
54,130
Fo each 1% dec ease in body
weigh , s udies epo ed 1% dec ease in li e a
con en .
123
The e ec was also mo e p o ound when base-
line BMI was highe .
120
Howe e , imp o emen s in li e
s ea osis we e also epo ed in he absence o weigh
loss,
56,131–133
sugges ing ha exe cise exe s bene icial
e ec s on li e s ea osis ha a e independen o weigh
loss.
54
This may be, in pa , explained by a mo e consis-
en imp o emen in isce al/abdominal a wi h p ese a-
ion o muscle mass,
56,127,130,132,134–137
in insulin
esis ance and lipid p o ile,
135,136,138–140
and modi ica ion
o in e -o gan c oss- alk wi h a a o able cy okine exp es-
sion ( o example, adiponec in and myos a in) and educ-
ion o in lamma ion and oxida i e s ess,
141
a e an
exe cise in e en ion.
A p edic o o he e icacy o an exe cise in e en ion
in educing li e a was baseline ca dio espi a o y i ness,
independen ly o o al and isce al adipose issue loss o
exe cise in ensi y.
142
Ca dio espi a o y i ness p obably
e lec ed he unc ional consequences o gene ics and
ecen physical ac i i y habi s.
The bene icial e ec s o exe cise on li e a we e
ans e sal ac oss he li espan, wi h posi i e esul s om
s udies on adolescen s
143
o he elde ly.
144
Howe e , he
e ec seemed o be mo e p onounced in he elde ly.
Exe cise was also bene icial in pa ien s wi h MAFLD
who had no mal weigh a baseline.
7
h ps://doi.o g/10.2147/DMSO.S304357
Do eP ess
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy 2021:14
3634
Machado Do ep ess
Powe ed by TCPDF (www. cpd .o g)Powe ed by TCPDF (www. cpd .o g)
Table 2 Randomized Con olled S udies E alua ing he E ec o Ae obic Exe cise on MAFLD
Re e ence Coun y N In e en ion Con ols Main Findings
In ensi y Sessions/
Week
Du a ion
Sulli an S,
2012
131
USA 19 obese
MAFLD
pa ien s
45–55 VO
2
peak, 30–60
minu es
5 16 No exe cise ● Exe cise ↓ IHLC (10.3±4.6%)
● Exe cise had no e ec on weigh o
% o body a
Hallswo h
K, 2015
33
UK 23 MAFLD
pa ien s
H-I in e al
aining
3 12 weeks S anda d o
ca e
● Exe cise associa ed wi h:
● ↓ li e a and whole body a mass
● ↓ ALT and AST
● ↑ ea ly dias olic illing a e
● No e ec on glucose o lipid
me abolism
Kea ing SE,
2015
58
Aus alia 48 inac i e
o e weigh /
obese adul s
1. L/M-I (50% VO
2
peak),
60 min, 4x/week
2. H-I (70% VO
2
peak),
45 min, 3x/week
3. L/M-I (50% VO
2
peak),
45 min, 3x/week
8 weeks No exe cise ● L/M-I, 60 min, 4x/week: ↓ IHLC 2.62
±1.00%, ↓ VAT 386.8±119.5 cm
2
● H-I, 45 min, 3x/week: ↓ IHLC 2.38
±0.73%, ↓ VAT 258.4±87.2 cm
2
● L/M-I, 45 min, 3x/week: ↓ IHLC 0.84
±0.45%, ↓ VAT 212.9±105.5 cm
2
● Placebo: ↑ IHLC 1.10±0.62%, ↑ VAT
92.6±83.5 cm
2
Zhang HS,
2016
126
China 220 MAFLD
pa ien s
wi h cen al
obesi y
1. H-I: 65–80%
maximal HR
2. M-I: 45–55%
maximal HR
150
minu es
6 mon hs No exe cise ● No di e ence on IHLC in M-I s
H-I exe cise, e en hough H-I exe cise
associa ed wi h highe dec ease in
body weigh
● No e ec on amino ans e ases
Shojaee-
Mo adie F,
2016
127
UK 27
seden a y
MAFLD
pa ien s
1 hou a 40–
60% HR
ese e
4–5 16 weeks Con en ional
li e-s yle
ad ice
● Exe cise e sus con ol ↓ IHLC,
isce al a and subcu aneous
abdominal a and ↑ VLDL clea ance
Cu hbe son
DS, 2016
140
UK 69 MAFLD
pa ien s
30% HR
ese e 30
minu es →
60% HR
ese e 45
minu es
3 → 5 16 weeks Counseling ● G ea e ↓ o IHLC in in e en ion
g oup (4.7% [0.01–9.4]), imp o emen
on insulin sensi i i y and SC
abdominal a
Rezende R,
2016
132
B azil 40
seden a y
pos -
menopausal
women
T eadmill
ae obic
exe cise
120
minu es
24 weeks No exe cise ● Exe cise associa ed wi h ↓ wais
ci cum e ence
● Exe cise did no associa e wi h
imp o emen s on s ea osis (by CAP-
Fib oscan) o glucose me abolism
Cheng S,
2017
139
China 115 pa ien s
wi h
MAFLD and
IR, 50–65
yea s
60–75% VO
2
max, 30–60
minu es
± ibe -
en iched die
2–3 8.6
mon hs
No
in e en ion
● E ec on IHLC:
● exe cise alone: ↓ 24.4%
● die alone: ↓ 23.2%
● exe cise + die : ↓ 47.9%
● no in e en ion: ↓ 20.9%
● Only exe cise associa ed wi h ↓
HbA1c
(Con inued)
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy 2021:14 h ps://doi.o g/10.2147/DMSO.S304357
Do eP ess
3635
Do ep ess Machado
Powe ed by TCPDF (www. cpd .o g)Powe ed by TCPDF (www. cpd .o g)
73. Be gs öm J, He mansen L, Hul man E, Sal in B. Die , muscle
glycogen and physical pe o mance. Ac a Physiol Scand. 1967;71
(2–3):140–150. doi:10.1111/j.1748-1716.1967. b03720.x
74. Ca ee GD, Fa a RP. Exe cise aining induces glycogen spa ing
du ing exe cise by old a s. J Appl Physiol. 1988;64(1):259–265.
doi:10.1152/jappl.1988.64.1.259
75. Wol e RR, Klein S, Ca a o F, Webe JM. Role o iglyce ide- a y
acid cycle in con olling a me abolism in humans du ing and a e
exe cise. Am J Physiol. 1990;258(2 P 1):E382–E389.
76. Wa MJ, Heigenhause GJF, Sp ie LL. In amuscula iacylgly-
ce ol u iliza ion in human skele al muscle du ing exe cise: is he e
a con o e sy? J Appl Physiol. 2002;93(4):1185–1195. doi:10.11
52/japplphysiol.00197.2002
77. Johnson NA, Kea ing SE, Geo ge J. Exe cise and he li e :
implica ions o he apy in a y li e diso de s. Semin Li e
Dis. 2012;32(1):65–79. doi:10.1055/s-0032-1306427
78. De lin JT, Ho on ES. E ec s o p io high-in ensi y exe cise
on glucose me abolism in no mal and insulin- esis an men.
Diabe es. 1985;34(10):973–979. doi:10.2337/diab.34.10.973
79. Bhanji RA, Na ayanan P, Allen AM, Malhi H, Wa KD.
Sa copenia in hiding: he isk and consequence o unde es ima -
ing muscle dys unc ion in nonalcoholic s ea ohepa i is.
Hepa ology. 2017;66(6):2055–2065. doi:10.1002/hep.29420
80. Huh JY. The ole o exe cise-induced myokines in egula ing
me abolism. A ch Pha m Res. 2018;41(1):14–29. doi:10.1007/
s12272-017-0994-y
81. Li F, Li Y, Duan Y, Hu CAA, Tang Y, Yin Y. Myokines and
adipokines: in ol emen in he c oss alk be ween skele al muscle
and adipose issue. Cy okine G ow h Fac o Re . 2017;33:73–82.
doi:10.1016/j.cy og .2016.10.003
82. Konopka AR, Wol CA, Sue MK, Ha be MP. Rela ionship be ween
in e muscula adipose issue in il a ion and myos a in be o e and
a e ae obic exe cise aining. Am J Physiol Regula In eg Comp
Physiol. 2018;315(3):R461–R468. doi:10.1152/ajp egu.00030.2018
83. Deloglu W, Caligiu i A, P o enzano A, e al. Myos a in egula es
he ib ogenic pheno ype o hepa ic s ella e cells ia c-jun
N- e minal kinase ac i a ion. Diges Li e Dis. 2019;51
(10):1400–1408. doi:10.1016/j.dld.2019.03.002
84. Fische CP. In e leukin-6 in acu e exe cise and aining: wha is
he biological ele ance? Exe c Immunol Re . 2006;12:6–33.
85. S eensbe g A, Fische CP, Kelle C, Mølle K, Pede sen BK. IL-6
enhances plasma IL-1 a, IL-10, and co isol in humans. Am
J Physiol Endoc inol Me ab. 2003;51(2):E433–E437. doi:10.11
52/ajpendo.00074.2003
86. Thy aul JP, Rec o RS, Up e g o e GM, e al. Ra s selec i ely
b ed o low ae obic capaci y ha e educed hepa ic mi ochond ial
oxida i e capaci y and suscep ibili y o hepa ic s ea osis and
inju y. J Physiol. 2009;587(8):1805–1916. doi:10.1113/jphysiol.
2009.169060
87. Fuen e FP, Quezada L, Sepúl eda C, e al. Exe cise egula es lipid
d ople dynamics in no mal and a y li e . Biochim E Biophys
Ac a Mol Cell Biol Lipids. 2019;1864(12):158519. doi:10.1016/j.
bbalip.2019.158519
88. Rec o RS, Thy aul JP, Mo is RT, e al. Daily exe cise inc eases
hepa ic a y acid oxida ion and p e en s s ea osis in O suka
Long-E ans Tokushima Fa y a s. Am J Physiol Gas oen e ol
Li e Physiol. 2008;294(3):G619–G626. doi:10.1152/ajpgi.004
28.2007
89. Pe idou A, Tsalouhidou S, Tsalis G, Schulz T, Michna H,
Mougios V. Long- e m exe cise inc eases he DNA binding ac i -
i y o pe oxisome p oli e a o -ac i a ed ecep o gamma in a
adipose issue. Me abolism. 2007;56(8):1029–1036. doi:10.1016/
j.me abol.2007.03.011
90. Rec o RS, Thy aul JP, Laye MJ, e al. Cessa ion o daily exe -
cise d ama ically al e s p ecu so s o hepa ic s ea osis in O suka
Long-E ans Tokushima Fa y (OLETF) a s. J Physiol. 2008;586
(17):4241–4249. doi:10.1113/jphysiol.2008.156745
91. Rec o RS, Up e g o e GM, Mo is EM, e al. Daily exe cise s.
calo ic es ic ion o p e en ion o nonalcoholic a y li e dis-
ease in he OLETF a model. Am J Physiol Gas oen e ol Li e
Physiol. 2011;300(5):G874–G883. doi:10.1152/ajpgi.00510.2010
92. Linden MA, Sheldon RD, Mee s GM, e al. Ae obic exe cise aining
in he ea men o non-alcoholic a y li e disease ela ed ib osis.
J Physiol. 2016;594(18):5271–5284. doi:10.1113/JP272235
93. Gomez-Cab e a MC, Domenech E, Viña J. Mode a e exe cise is
an an ioxidan : up egula ion o an ioxidan genes by aining.
F ee Radic Biol Med. 2008;44(2):126–131. doi:10.1016/j.
ee adbiomed.2007.02.001
94. Tung BT, Rod iguez-Bies E, Thanh HN, e al. O gan and
issue-dependen e ec o es e a ol and exe cise on an ioxidan
de enses o old mice. Aging Clin Expe imen Res. 2015;27
(6):775–783. doi:10.1007/s40520-015-0366-8
95. Lima FD, S amm DN, Della-Pace ID, e al. Swimming aining
induces li e mi ochond ial adap a ions o oxida i e s ess in a s
submi ed o epea ed exhaus i e swimming bou s. PLoS One.
2013;8(2):e55668. doi:10.1371/jou nal.pone.0055668
96. Lima TI, Mon ei o IC, Valença S, e al. E ec o exe cise aining
on li e an ioxidan enzymes in STZ-diabe ic a s. Li e Sci.
2015;128:64–71. doi:10.1016/j.l s.2015.01.031
97. A ula CPR, Fe nandes G. Modula ion o an ioxidan enzymes and
lipid pe oxida ion in sali a y gland and o he issues in mice by
mode a e eadmill exe cise. Aging. 1999;11(4):246–252.
98. Vendi i P, Di Meo S. E ec o aining on an ioxidan capaci y,
issue damage, and endu ance o adul male a s. In J Spo s Med.
1997;18(7):497–502. doi:10.1055/s-2007-972671
99. Gleeson M, Bishop NC, S ensel DJ, Lindley MR, Mas ana SS,
Nimmo MA. The an i-in lamma o y e ec s o exe cise: mechan-
isms and implica ions o he p e en ion and ea men o disease.
Na Re Immunol. 2011;11(9):607–615. doi:10.1038/n i3041
100. Kawanishi N, Yano H, Mizokami T, Takahashi M, Oyanagi E,
Suzuki K. Exe cise aining a enua es hepa ic in lamma ion, ib osis
and mac ophage in il a ion du ing die induced-obesi y in mice. B ain
Beha Immun. 2012;26(6):931–941. doi:10.1016/j.bbi.2012.04.006
101. El-Kade SMA, Al-Ji i O, Al-Sh ee FM. Ma ke s o li e unc ion
and in lamma o y cy okines modula ion by ae obic e sus esis ed
exe cise aining o nonalcoholic s ea ohepa i is pa ien s. A ican
Heal h Sci. 2014;14(3):551–557. doi:10.4314/ahs. 14i3.8
102. Gleeson M, McFa lin B, Flynn M. Exe cise and oll-like
ecep o s. Exe c Immunol Re . 2006;12:34–53.
103. Wang J, Song H, Tang X, e al. E ec o exe cise aining
in ensi y on mu ine T- egula o y cells and accina ion esponse.
Scand J Med Sci Spo s. 2012;22(5):643–652. doi:10.1111/j.1600-
0838.2010.01288.x
104. Guo R, Liong EC, So KF, Fung ML, Tipoe GL. Bene icial
mechanisms o ae obic exe cise on hepa ic lipid me abolism in
non-alcoholic a y li e disease. Hepa obil Panc ea Dis In .
2015;14(2):139–144. doi:10.1016/S1499-3872(15)60355-1
105. Bo e is A, Na a o A. Sys emic and mi ochond ial adap i e
esponses o mode a e exe cise in oden s. F ee Radic Biol Med.
2008;44(2):224–229. doi:10.1016/j. ee adbiomed.2007.08.015
106. Gonçal es IO, Oli ei a PJ, Ascensão A, Magalhães J. Exe cise as
a he apeu ic ool o p e en mi ochond ial degene a ion in nonalco-
holic s ea ohepa i is. Eu J Clin In es . 2013;43(11):1184–1194.
107. Gonçal es IO, Passos E, Rocha-Rod igues S, e al. Physical exe cise
p e en s and mi iga es non-alcoholic s ea ohepa i is-induced li e
mi ochond ial s uc u al and bioene ge ics impai men s.
Mi ochond ion. 2014;15:40–51. doi:10.1016/j.mi o.2014.03.012
h ps://doi.o g/10.2147/DMSO.S304357
Do eP ess
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy 2021:14
3642
Machado Do ep ess
Powe ed by TCPDF (www. cpd .o g)Powe ed by TCPDF (www. cpd .o g)

108. Gonçal es IO, Passos E, Diogo CV, e al. Exe cise mi iga es
mi ochond ial pe meabili y ansi ion po e and quali y con ol
mechanisms al e a ions in nonalcoholic s ea ohepa i is. Appl
Physiol Nu Me abol. 2016;41(3):298–306. doi:10.1139/apnm-
2015-0470
109. Fealy CE, Haus JM, Solomon TPJ, e al. Sho - e m exe cise
educes ma ke s o hepa ocy e apop osis in nonalcoholic a y
li e disease. J Appl Physiol. 2012;113(1):1–6. doi:10.1152/
japplphysiol.00127.2012
110. Hajighasem A, Fa zanegi P, Mazahe i Z. E ec s o combined
he apy wi h es e a ol, con inuous and in e al exe cises on
apop osis, oxida i e s ess, and in lamma o y bioma ke s in he
li e o old a s wi h non-alcoholic a y li e disease. A ch
Physiol Biochem. 2019;125(2):142–149. doi:10.1080/
13813455.2018.1441872
111. Pigue AC, Sa an U, Simillion C, e al. Regula exe cise
dec eases li e umo s de elopmen in hepa ocy e-speci ic
PTEN-de icien mice independen ly o s ea osis. J Hepa ol.
2015;62(6):1296–1303. doi:10.1016/j.jhep.2015.01.017
112. Gua ino M, Kuma P, Felse A, e al. Exe cise a enua es he
ansi ion om a y li e o s ea ohepa i is and educes umo
o ma ion in mice. Cance s. 2020;12(6):1407. doi:10.3390/
cance s12061407
113. A ian i A, Pok S, Ba n V, e al. Exe cise e a ds hepa oca cino-
genesis in obese mice independen ly o weigh con ol. J Hepa ol.
2020;73(1):140–148. doi:10.1016/j.jhep.2020.02.006
114. Ke n T, Blond MB, Hansen TH, e al. S uc u ed exe cise al e s
he gu mic obio a in humans wi h o e weigh and
obesi y-A andomized con olled ial. In J Obes. 2020;44
(1):125–135. doi:10.1038/s41366-019-0440-y
115. Hughes A, Dahmus J, Ri as G, e al. Exe cise aining e e ses
gu dysbiosis in pa ien s wi h biopsy-p o en nonalcoholic s ea o-
hepa i is: a p oo o concep s udy. Clin Gas oen e ol Hepa ol.
2020;S1542(20):31222–31224.
116. Hube Y, P i mann D, Gebha d I, e al. Imp o emen o
non-in asi e ma ke s o NAFLD om an indi idualised,
web-based exe cise p og am. Alimen Pha macol The . 2019;50
(8):930–939. doi:10.1111/ap .15427
117. Mo iani KK, Collado MC, Eskelinen JJ, e al. Exe cise aining
modula es gu mic obio a p o ile and imp o es endo oxemia. Med
Sci Spo s Exe c. 2020;52(1):94–104. doi:10.1249/MSS.000
0000000002112
118. Ca bajo-Pescado S, Po as D, Ga cıá-Media illa MV, e al.
Bene icial e ec s o exe cise on gu mic obio a unc ionali y
and ba ie in eg i y, and gu -li e c oss alk in an in i o model
o ea ly obesi y and non-alcoholic a y li e disease. Dis Models
Mechan. 2019;12(5):dmm039206. doi:10.1242/dmm.039206
119. Kea ing SE, Hacke DA, Geo ge J, Johnson NA. Exe cise and
non-alcoholic a y li e disease: a sys ema ic e iew and
me a-analysis. J Hepa ol. 2012;57(1):157–166. doi:10.1016/j.
jhep.2012.02.023
120. O ci LA, Ga iani K, Oldani G, Delaune V, Mo el P, Toso C.
Exe cise-based in e en ions o non-alcoholic a y li e disease:
a me a- analysis and me a- eg ession. Clin Gas oen e ol Hepa ol.
2016;14(10):1398–1411. doi:10.1016/j.cgh.2016.04.036
121. Kenneally S, Sie JH, Moo e JB. E icacy o die a y and physical
ac i i y in e en ion in non-alcoholic a y li e disease:
a sys ema ic e iew. BMJ Open Gas oen e ol. 2017;4(1):
e000139–e000151. doi:10.1136/bmjgas -2017-000139
122. Hashida R, Kawaguchi T, Bekki M, e al. Ae obic s. esis ance
exe cise in non-alcoholic a y li e disease: a sys ema ic e iew.
J Hepa ol. 2017;66(1):142–152. doi:10.1016/j.jhep.2016.08.023
123. Sa gean JA, G ay LJ, Bodicoa DH, e al. The e ec o exe cise
aining on in ahepa ic iglyce ide and hepa ic insulin sensi i -
i y: a sys ema ic e iew and me a-analysis. Obes Re . 2018;19
(10):1446–1459. doi:10.1111/ob .12719
124. Sma NA, King N, McFa lane JR, G aham PL, Diebe g G. E ec
o exe cise aining on li e unc ion in adul s who a e o e weigh
o exhibi a y li e disease: a sys ema ic e iew and
me a-analysis. B J Spo s Med. 2018;52(13):834–843. doi:10.
1136/bjspo s-2016-096197
125. Wang ST, Zheng J, Peng HW, e al. Physical ac i i y in e en ion o
non-diabe ic pa ien s wi h non-alcoholic a y li e disease: a
me a-analysis o andomized con olled ials. BMC Gas oen e ol.
2020;20(1):66–77. doi:10.1186/s12876-020-01204-3
126. Zhang HJ, Pan LL, Ma ZM, e al. Long- e m e ec o exe cise on
imp o ing a y li e and ca dio ascula isk ac o s in obese
adul s: a 1-yea ollow-up s udy. Diabe es Obes Me ab. 2017;19
(2):284–289. doi:10.1111/dom.12809
127. Shojaee-Mo adie F, Cu hbe son DJ, Ba e M, e al. Exe cise
aining educes li e a and inc eases a es o VLDL clea ance
bu no VLDL p oduc ion in NAFLD. J Clin Endoc inol Me abol.
2016;101(11):4219–4228. doi:10.1210/jc.2016-2353
128. Why e MB, Shojaee-Mo adie F, Sha a SE, e al. HDL-apoA-I
kine ics in esponse o 16 wk o exe cise aining in men wi h
nonalcoholic a y li e disease. Am J Physiol Endoc inol Me ab.
2020;318(6):E839–E847. doi:10.1152/ajpendo.00019.2020
129. De ies MC, Samjoo IA, Hamadeh MJ, Ta nopolsky MA. E ec
o endu ance exe cise on hepa ic lipid con en , enzymes, and
adiposi y in men and women. Obesi y. 2008;16(10):2281–2288.
doi:10.1038/oby.2008.358
130. B ouwe s B, Sch auwen-Hinde ling VB, Jelenik T, e al. Exe cise
aining educes in ahepa ic lipid con en in people wi h and people
wi hou nonalcoholic a y li e . Am J Physiol Endoc inol Me ab.
2018;314(2):E165–E173. doi:10.1152/ajpendo.00266.2017
131. Sulli an S, Ki k EP, Mi endo e B, Pa e son BW, Klein S.
Randomized ial o exe cise e ec on in ahepa ic iglyce ide
con en and lipid kine ics in nonalcoholic a y li e disease.
Hepa ology. 2012;55(6):1738–1745. doi:10.1002/hep.25548
132. Rezende REF, Dua e SMB, S e ano JT, e al. Randomized clinical
ial: bene i s o ae obic physical ac i i y o 24 weeks in pos me-
nopausal women wi h nonalcoholic a y li e disease. Menopause.
2016;23(8):876–883. doi:10.1097/GME.0000000000000647
133. Winn NC, Ying L, Rec o RS, Pa ks EJ, Ibdah JA, Kanaley JA.
Ene gy-ma ched mode a e and high in ensi y exe cise aining
imp o es nonalcoholic a y li e disease isk independen o changes
in body mass o abdominal adiposi y – a andomized ial. Me abolism.
2018;78:128–140. doi:10.1016/j.me abol.2017.08.012
134. Dekke MJ, Lee SJ, Hudson R, e al. An exe cise in e en ion
wi hou weigh loss dec eases ci cula ing in e leukin-6 in lean and
obese men wi h and wi hou ype 2 diabe es melli us. Me abolism.
2007;56(3):332–338. doi:10.1016/j.me abol.2006.10.015
135. Abdelbasse WK, Tan awy SA, Kamel DM, Alqah ani BA,
Soliman GS. A andomized con olled ial on he e ec i eness o
8-week high-in ensi y in e al exe cise on in ahepa ic iglyce ides,
isce al lipids, and heal h- ela ed quali y o li e in diabe ic obese
pa ien s wi h nonalcoholic a y li e disease. Medicine. 2019;98
(12):e14918. doi:10.1097/MD.0000000000014918
136. Abdelbasse WK, Tan awy SA, Kamel DM, e al. E ec s o
high-in ensi y in e al and mode a e- in ensi y con inuous ae obic
exe cise on diabe ic obese pa ien s wi h nonalcoholic a y li e
disease: a compa a i e andomized con olled ial. Medicine.
2020;99(10):e19471. doi:10.1097/MD.0000000000019471
137. Bacchi E, Neg i C, Ta ghe G, e al. Bo h esis ance aining and
ae obic aining educe hepa ic a con en in ype 2 diabe ic
subjec s wi h nonalcoholic a y li e disease ( he RAED2 ando-
mized ial). Hepa ology. 2013;58(4):1287–1295. doi:10.1002/
hep.26393
138. Cassidy S, Thoma C, Wo hswo h K, e al. High in ensi y in e mi en
exe cise imp o es ca diac s uc u e and unc ion and educes li e a
in pa ien s wi h ype 2 diabe es: a andomised con olled ial.
Diabe ologia. 2016;59(1):56–66. doi:10.1007/s00125-015-3741-2
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy 2021:14 h ps://doi.o g/10.2147/DMSO.S304357
Do eP ess
3643
Do ep ess Machado
Powe ed by TCPDF (www. cpd .o g)Powe ed by TCPDF (www. cpd .o g)
139. Cheng S, Ge J, Zhao C, e al. E ec o ae obic exe cise and die
on li e a in p e-diabe ic pa ien s wi h non-alcoholic- a y-li e -
disease: a andomized con olled ial. Sci Rep. 2017;7(1):15952.
doi:10.1038/s41598-017-16159-x
140. Cu hbe son DJ, Shojaee-Mo adie F, Sp ung VS, e al.
Dissocia ion be ween exe cise-induced educ ion in li e a and
changes in hepa ic and pe iphe al glucose homoeos asis in obese
pa ien s wi h non-alcoholic a y li e disease. Clin Sci. 2016;130
(2):93–104. doi:10.1042/CS20150447
141. Oh KW, Tsujimo o T, Kim B, e al. Weigh -loss-independen
bene i s o exe cise on li e s ea osis and s i ness in Japanese
men wi h NAFLD. JHEP Rep. 2021;3(3):100253. doi:10.1016/j.
jhep .2021.100253
142. Kan a zis K, Thame C, Pe e A, e al. High ca dio espi a o y
i ness is an independen p edic o o he educ ion in li e a
du ing a li es yle in e en ion in non-alcoholic a y li e disease.
Gu . 2009;58(9):1281–1288. doi:10.1136/gu .2008.151977
143. an de Heijden GJ, Wang ZJ, Chu ZD, e al. A 12-week ae obic
exe cise p og am educes hepa ic a accumula ion and insulin
esis ance in obese, Hispanic adolescen s. Obesi y. 2010;18
(2):384–390. doi:10.1038/oby.2009.274
144. Finucane FM, Sha p SJ, Pu slow LR, e al. The e ec s o ae obic
exe cise on me abolic isk, insulin sensi i i y and in ahepa ic
lipid in heal hy olde people om he He o dshi e Coho
S udy: a andomised con olled ial. Diabe ologia. 2010;53
(4):624–631. doi:10.1007/s00125-009-1641-z
145. Na h P, Panig ahi MK, Sahu MK, e al. E ec o exe cise on
NAFLD and i s isk ac o s: compa ison o mode a e e sus low
in ensi y exe cise. J Clin T ansl Hepa ol. 2020;8(2):120–126.
doi:10.14218/JCTH.2019.00012
146. S Geo ge A, Bauman A, Johns on A, Fa ell G, Chey T,
Geo ge J. Independen e ec s o physical ac i i y in pa ien s
wi h nonalcoholic a y li e disease. Hepa ology. 2009;50
(1):68–76. doi:10.1002/hep.22940
147. Kea ing SE, Geo ge J, Johnson NA. The bene i s o exe cise o
pa ien s wi h non-alcoholic a y li e disease. Expe Re
Gas oen e ol Hepa ol. 2015;9(10):1247–1250. doi:10.1586/
17474124.2015.1075392
148. Zhang HJ, He J, Pan LL, e al. E ec s o mode a e and igo ous
exe cise on nonalcoholic a y li e disease: a andomized clinical
ial. JAMA In e n Med. 2016;176(8):1074–1082. doi:10.1001/
jamain e nmed.2016.3202
149. Oh S, Shida T, Yamagishi K, e al. Mode a e o igo ous physical
ac i i y olume is an impo an ac o o managing nonalcoholic
a y li e disease: a e ospec i e s udy. Hepa ology. 2015;61
(4):1205–1215. doi:10.1002/hep.27544
150. Bake CJ, Ma inez-Huenchullan FS, D’Souza M, e al. E ec o
exe cise on hepa ic s ea osis: a e bene i s seen wi hou die a y
in e en ion? A sys ema ic e iew and me a-analysis. J Diabe es.
2021;13(1):63–77. doi:10.1111/1753-0407.13086
151. Tamu a Y, Tanaka Y, Sa o F, e al. E ec s o die and exe cise on
muscle and li e in acellula lipid con en s and insulin sensi i i y
in ype 2 diabe ic pa ien s. J Clin Endoc inol Me abol. 2005;90
(6):3191–3196. doi:10.1210/jc.2004-1959
152. Shah K, S u lebam A, Hil on TN, Sinaco e DR, Klein S,
Villa eal DT. Die and exe cise in e en ions educe in ahepa ic
a con en and imp o e insulin sensi i i y in obese olde adul s.
Obesi y. 2009;17(12):2162–2168. doi:10.1038/oby.2009.126
153. La son-Meye DE, Newcome BR, Heilb onn LK, e al. E ec o
6-mon h calo ie es ic ion and exe cise on se um and li e lipids
and ma ke s o li e unc ion. Obesi y. 2008;16(6):1155–1362.
doi:10.1038/oby.2008.201
154. Goodpas e BH, Delany JP, O o AD, e al. E ec s o die and
physical ac i i y in e en ions on weigh loss and ca diome abolic
isk ac o s in se e ely obese adul s: a andomized ial. JAMA.
2010;304(16):1795–1802. doi:10.1001/jama.2010.1505
155. Linden MA, Fle che JA, Mo is EM, e al. T ea ing NAFLD in
OLETF a s wi h igo ous-in ensi y in e al exe cise aining.
Med Sci Spo s Exe c. 2015;47(3):556–567. doi:10.1249/
MSS.0000000000000430
156. Hickman IJ, By ne NM, C oci I, e al. A pilo andomised s udy
o he me abolic and his ological e ec s o exe cise in
non-alcoholic s ea ohepa i is. J Diabe es Me ab. 2013;4
(8):1000300.
157. O’Go man P, Naimimohasses S, Monaghan A, e al. Imp o emen
in his ological endpoin s o MAFLD ollowing a 12-week ae obic
exe cise in e en ion. Alimen Pha macol The . 2020;52
(8):1387–1398.
158. Oh S, So R, Shida T, e al. High-in ensi y ae obic exe cise
imp o es bo h hepa ic a con en and s i ness in seden a y
obese men wi h nonalcoholic a y li e disease. Sci Rep.
2017;7:43029–43041. doi:10.1038/s ep43029
159. Kea ing SE, Adams LA. Exe cise in NAFLD: jus do i .
J Hepa ol. 2016;65(4):671–673. doi:10.1016/j.jhep.2016.06.022
160. Wilson JM, Loenneke JP, Jo E, Wilson GJ, Zou dos MC, Kim JS.
The e ec s o endu ance, s eng h, and powe aining on muscle
ibe ype shi ing. J S eng h Condi ion Res Publish. 2012;26
(6):1724–1729. doi:10.1519/JSC.0b013e318234eb6
161. Yang Z, Sco CA, Mao C, Tang J, Fa me AJ. Resis ance exe -
cise e sus ae obic exe cise o ype 2 diabe es: a sys ema ic
e iew and me a-analysis. Spo s Med. 2014;44(4):487–499.
doi:10.1007/s40279-013-0128-8
162. Ca doso CG, Gomides RS, Quei oz ACC, e al. Acu e and
ch onic e ec s o ae obic and esis ance exe cise on ambula o y
blood p essu e. Clinics. 2010;65(3):317–325. doi:10.1590/S1807-
59322010000300013
163. Hughes DC, Elle sen S, Baa K. Adap a ions o endu ance and
s eng h aining. Cold Sp ing Ha b Pe spec Med. 2018;8(6):
a029769. doi:10.1101/cshpe spec .a029769
164. Slen z CA, Ba eman LA, Willis LH, e al. E ec s o ae obic s.
esis ance aining on isce al and li e a s o es, li e enzymes,
and insulin esis ance by HOMA in o e weigh adul s om
STRRIDE AT/RT. Am J Physiol Endoc inol Me ab. 2011;301
(5):E1033–E1039. doi:10.1152/ajpendo.00291.2011
165. Shamsoddini A, Sobhani V, Cheh eh MEG, Ala ian SM, Za ee A.
E ec o ae obic and esis ance exe cise aining on li e
enzymes and hepa ic a in I anian men wi h nonalcoholic a y
li e disease. Hepa Mon. 2015;15(10):e31434. doi:10.5812/
hepa mon.31434
166. Kim HJ, Lee HJ, So B, Son JS, Yoon D, Song W. E ec o
ae obic aining and esis ance aining on ci cula ing i isin le el
and hei associa ion wi h change o body composi ion in o e -
weigh /obese adul s: a pilo s udy. Physiolog Res. 2016;65
(2):271–279. doi:10.33549/physiol es.932997
167. Ghama cheh eh ME, Shamsoddini A, Ala ian SM. In es iga ing
he impac o eigh weeks o ae obic and esis ance aining on
blood lipid p o ile in elde ly wi h non-alcoholic a y li e dis-
ease: a andomized clinical ial. Gas oen e ol Hepa ol Bed
Bench. 2019;12(3):190–196.
168. Hallswo h K, Fa akho a G, Hollingswo h KG, e al. Resis ance
exe cise educes li e a and i s media o s in non-alcoholic a y
li e disease independen o weigh loss. Gu . 2011;60
(9):1278–1283. doi:10.1136/gu .2011.242073
169. Zelbe -Sagi S, Buch A, Yeshua H, e al. E ec o esis ance
aining on non-alcoholic a y-li e disease a
andomized-clinical ial. Wo ld J Gas oen e ol. 2014;20
(15):4382–4392. doi:10.3748/wjg. 20.i15.4382
170. Ga be CE, Blissme B, Deschenes MR, e al. Quan i y and
quali y o exe cise o de eloping and main aining ca dio espi a-
o y, musculoskele al, and neu omo o i ness in appa en ly
heal hy adul s: guidance o p esc ibing exe cise. Med Sci
Spo s Exe c. 2011;43(7):1334–1359.
h ps://doi.o g/10.2147/DMSO.S304357
Do eP ess
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy 2021:14
3644
Machado Do ep ess
Powe ed by TCPDF (www. cpd .o g)Powe ed by TCPDF (www. cpd .o g)
171. Younossi ZM, Co ey KE, Lim JK. AGA clinical p ac ice upda e
on li es yle modi ica ion using die and exe cise o achie e weigh
loss in he managemen o nonalcoholic a y li e disease: expe
e iew. Gas oen e ology. 2021;160(3):912–918. doi:10.1053/j.
gas o.2020.11.051
172. Chalasani N, Younossi ZM, La ine JE, e al. The diagnosis and
managemen o nonalcoholic a y li e disease: p ac ice guidance
om he Ame ican associa ion o he s udy o li e diseases.
Hepa ology. 2018;67(1):328–357.
173. Ma chesini G, Day CP, Du ou JF, e al. EASL-EASD-EASO
clinical p ac ice guidelines o he managemen o non-alcoholic
a y li e disease. J Hepa ol. 2016;64(6):1388–1402.
174. Glen J, Flo os L, Day CP, P yke R. Non-alcoholic a y li e
disease (NAFLD): summa y o NICE guidance. BMJ. 2016;354:
i4428. doi:10.1136/bmj.i4428
175. LaB ecque DR, Abbas Z, Anania F, e al. Wo ld Gas oen e ology
O ganisa ion global guidelines: nonalcoholic a y li e disease
and nonalcoholic s ea ohepa i is. J Clin Gas oen e ol. 2014;48
(6):467–473. doi:10.1097/MCG.0000000000000116
176. Rognmo Ø, Mohold T, Bakken H, e al. Ca dio ascula isk o
high- e sus mode a e-in ensi y ae obic exe cise in co ona y hea
disease pa ien s. Ci cula ion. 2012;126(12):1436–1440.
doi:10.1161/CIRCULATIONAHA.112.123117
177. Ma chesini G, Pe a S, Dalle G a e R. Die , weigh loss, and li e
heal h in nonalcoholic a y li e disease: pa hophysiology, e i-
dence, and p ac ice. Hepa ology. 2016;63(6):2032–2043.
doi:10.1002/hep.28392
178. F i h J, Day CP, Robinson LE, Ellio C, Jones DEJ, New on JL.
Po en ial s a egies o imp o e up ake o exe cise in e en ions in
non-alcoholic a y li e disease. J Hepa ol. 2010;52(1):112–116.
doi:10.1016/j.jhep.2009.10.010
179. S ine JG, So iano C, Sch eibman I, e al. B eaking down ba ie s
o physical ac i i y in pa ien s wi h nonalcoholic a y li e
disease. Dig Dis Sci. 2020;1–8. doi:10.1007/s10620-020-06673-w
180. Aoike DT, Ba ia F, Kamimu a MA, Ammi a i A, Cuppa i L.
Home-based e sus cen e -based ae obic exe cise on ca diopul-
mona y pe o mance, physical unc ion, quali y o li e and quali y
o sleep o o e weigh pa ien s wi h ch onic kidney disease. Clin
Exp Neph ol. 2018;22(1):87–98. doi:10.1007/s10157-017-1429-2
181. Ande sen RE, Wadden TA, Ba le SJ, Zemel B, Ve de TJ,
F anckowiak SC. E ec s o li es yle ac i i y s s uc u ed ae obic
exe cise in obese women: a andomized ial. JAMA. 1999;281
(4):335–340. doi:10.1001/jama.281.4.335
182. Mange i F, Mon esi L, Fo lani G, Dalle G a e R, Ma chesini G.
A s anda d ball oom and La in dance p og am o imp o e i ness
and adhe ence o physical ac i i y in indi iduals wi h ype 2
diabe es and in obesi y. Diabe ol Me abol Synd . 2014;6:74.
doi:10.1186/1758-5996-6-74
183. Mosca iello S, Di Luzio R, Bugianesi E, e al. Cogni i e-
beha io al ea men o nonalcoholic a y li e disease:
a p opensi y sco e-adjus ed obse a ional s udy. Obesi y.
2011;19(4):763–770. doi:10.1038/oby.2010.254
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy Do ep ess
Publish you wo k in his jou nal
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy is
an in e na ional, pee - e iewed open-access jou nal commi ed o he
apid publica ion o he la es labo a o y and clinical indings in he
ields o diabe es, me abolic synd ome and obesi y esea ch. O iginal
esea ch, e iew, case epo s, hypo hesis o ma ion, expe opinion
and commen a ies a e all conside ed o publica ion. The manu-
sc ip managemen sys em is comple ely online and includes a e y
quick and ai pee - e iew sys em, which is all easy o use. Visi
h p://www.do ep ess.com/ es imonials.php o ead eal quo es om
published au ho s.
Submi you manusc ip he e: h ps://www.do ep ess.com/diabe es-me abolic-synd ome-and-obesi y- a ge s-and- he apy-jou nal
Diabe es, Me abolic Synd ome and Obesi y: Ta ge s and The apy 2021:14 Do eP ess
3645
Do ep ess Machado
Powe ed by TCPDF (www. cpd .o g)Powe ed by TCPDF (www. cpd .o g)