Analysis o he adiponec in pa adox in heal hy olde
people
Ca ina O. Walowski
1
, Ca in He pich
2,3,4
, Janna Ende le
1
, Wiebke B aun
1
, Ma cus Bo h
5
, Ma io Hasle
6
,
Man ed J. Mülle
1
, K is ina No man
2,3,4,7
& Anja Bosy-Wes phal
1
*
1
Ins i u e o Human Nu i ion and Food Science, Ch is ian-Alb ech s-Uni e si y, Kiel, Ge many;
2
Ins i u e o Nu i ional Science, Uni e si y o Po sdam, Nu he al, Ge many;
3
Depa men o Ge ia ics and Medical Ge on ology, Cha i é Uni e si ä smedizin Be lin, Co po a e membe o F eie Uni e si ä Be lin and Humbold -Uni e si ä zu Be lin,
Be lin, Ge many;
4
Depa men o Nu i ion and Ge on ology, Ge man Ins i u e o Human Nu i ion, Po sdam-Rehb ücke, Nu he al, Ge many;
5
Depa men o Radiology and
Neu o adiology, Uni e si y Medical Cen e Schleswig-Hols ein, Kiel, Ge many;
6
Applied S a is ics, Facul y o Ag icul u al and Nu i ional Sciences, Ch is ian-Alb ech s-
Uni e si y, Kiel, Ge many;
7
Ge man Cen e o Ca dio ascula Resea ch (DZHK), Pa ne Si e Be lin, Be lin, Ge many
Abs ac
Backg ound I emains unknown why adiponec in le els a e associa ed wi h poo physical unc ioning, skele al muscle
mass and inc eased mo ali y in olde popula ions.
Me hods In 190 heal hy adul s (59–86 yea s, BMI 17–37 kg/m
2
, 56.8% emale), whole body skele al muscle mass
(no malized by heigh , SMI, kg/m
2
), muscle and li e a we e de e mined by magne ic esonance imaging. Bone min-
e al con en (BMC) and densi y (BMD) we e assessed by dual X- ay abso p iome y (n= 135). Le els o insulin-like
g ow h ac o 1 (IGF-1), insulin, inflamma ion ma ke s, lep in and fib oblas g ow h ac o 21 we e measu ed as po en-
ial de e minan s o he ela ionship be ween adiponec in and body composi ion.
Resul s Highe adiponec in le els we e associa ed wi h a lowe SMI ( =0.23, P<0.01), BMC ( =0.17, P<0.05)
and li e a ( =0.20, P<0.05) in he o al popula ion and wi h highe muscle a in women ( = 0.27, P<0.01). By
con as , IGF-1 showed posi i e co ela ions wi h SMI ( = 0.33), BMD ( = 0.37) and BMC ( = 0.33) (all P<0.01)
and a nega i e co ela ion wi h muscle a ( =0.17, P<0.05). IGF-1 was nega i ely associa ed wi h age ( =0.21,
P<0.01) and wi h adiponec in ( =0.15, P<0.05). S epwise eg ession analyses e ealed ha IGF-1, insulin and
lep in explained 18% o he a iance in SMI, and IGF-1, lep in and age explained 16% o he a iance in BMC, whe eas
adiponec in did no con ibu e o hese models.
Conclusions Associa ions be ween highe adiponec in le els and lowe muscle o bone mass in heal hy olde adul s
may be explained by a dec ease in IGF-1 wi h inc easing adiponec in le els.
Keywo ds Adiponec in pa adox; Olde adul s; Skele al muscle mass; Muscle quali y; Bone; Li e a
Recei ed:
18
May
2022
; Re ised:
4
Oc obe
2022
; Accep ed:
25
Oc obe
2022
*Co espondence o: Anja Bosy-Wes phal, Ch is ian-Alb ech s-Uni e si ä zu Kiel, Ins i u ü Humane näh ung und Lebensmi elkunde, Düs e nb ooke Weg
17
,
24105
Kiel,
Ge many. Email: [email p o ec ed]e
In oduc ion
Adiponec in is an abundan pep ide ho mone p ima ily
sec e ed by adipose issue (AT), and o a lesse ex en by skel-
e al muscle (SM) and bone ma ow adipocy es ( o a e iew,
see Fazeli e al.
1
). I is well-known o imp o ing insulin sen-
si i i y as well as o an i-inflamma o y and an i-a he ogenic
p ope ies ( o a e iew, see Robinson e al.
2
). Se e al me a-
bolic and ca dio ascula diso de s including ype 2 diabe es,
me abolic synd ome ( o a e iew, see Di Chia a e al.
3
),
a he oscle osis
4
and non-alcoholic a y li e disease
5
a e
hus accompanied by hypoadiponec inaemia. As a myokine,
adiponec in ac s as a myogenic ac o h ough he pa icipa-
ion in muscle di e en ia ion and issue egene a ion, and
influencing he beha iou o muscle cells ( o a e iew, see
Gambe i e al.
6
). Accumula ing e idence also sugges s ha
ORIGINAL ARTICLE
© 2022 The Au ho s. Jou nal o Cachexia, Sa copenia and Muscle published by John Wiley & Sons L d on behal o Socie y on Sa copenia, Cachexia and Was ing Diso de s.
This is an open access a icle unde he e ms o he C ea i e Commons A ibu ion-NonComme cial-NoDe i s License, which pe mi s use and dis ibu ion in any medium,
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Jou nal o Cachexia, Sa copenia and Muscle 2023; 14: 270–278
Published online 18 No embe 2022 in Wiley Online Lib a y (wileyonlinelib a y.com) DOI: 10.1002/jcsm.13127
adiponec in p omo es os eoblas ogenesis, while simul a-
neously inhibi ing os eoclas ogenesis ( o a e iew, see Lewis
e al.
7
). I is he e o e causally enigma ic why adiponec in
le els a e nega i ely associa ed wi h SM, muscle densi y,
physical unc ioning
8
o bone mine al densi y (BMD)
9
among
olde adul s. Adiponec in le els we e shown o inc ease wi h
age
10
and a e e en associa ed wi h highe a es o ca dio as-
cula and all-cause mo ali y in olde popula ions.
11
The
so-called adiponec in pa adox he e o e sugges s ha adipo-
nec in may no exe beneficial e ec s in olde adul s.
Di e en explana ions o he adiponec in pa adox in
olde people ha e been discussed including adiponec in
esis ance,
12
compensa o y e ec s o adiponec in o subclin-
ical pa hologies, impai ed enal unc ion and dec eased he-
pa ic clea ance o adiponec in ( o a e iew, see Kalkman
13
).
In addi ion, adiponec in was p oposed o be a bioma ke o
ad e se ca abolic p ocesses (i.e., a low SM due o sa copenia
ela ed o aging,
8,14
o cachexia associa ed wi h ch onic in-
flamma ion and p e-exis ing illness
15,16
). I emains unknown
i highe adiponec in le els in olde adul s a e a cause o a
low muscle mass by media ing ca abolic p ocesses o a he
a consequence o ca abolic p ocesses ha lead o a lowe
SM. The ela ionship be ween adiponec in and de ailed body
composi ion analysis he e o e needs o be in es iga ed in
heal hy olde adul s wi hou ca abolic disease o impai ed e-
nal unc ion.
The aim o he p esen s udy was he e o e (i) o in es i-
ga e he associa ion be ween adiponec in le els and SM (by
whole body magne ic esonance imaging, (MRI)), muscle a
and s eng h o bone mass and bone densi y in heal hy
communi y-dwelling olde adul s and (ii) o iden i y po en ial
endoc ine de e minan s o adiponec in le els.
Me hods
S udy popula ion
The p esen s udy was conduc ed a he ‘Ge man Re e ence
Cen e o Body Composi ion’(Ins i u e o Human Nu i ion
and Food Science a he Uni e si y o Kiel, Ge many) be ween
2019 and 2020. Exclusion c i e ia we e oedema, acu e dis-
eases, hea ailu e, enal ailu e, in ake o diu e ics, pa alysis
(e.g., a e a s oke), neu odegene a i e diseases, umou s in
ea men , ampu a ion o limbs, elec ical and me allic
implan s, cu en alcohol abuse, no emo able pie cings
and la ge a oos on he a ms o legs (because o possible in-
e e ence wi h MRI examina ions) as well as medica ion,
which could influence body composi ion. Subjec s we e e-
c ui ed using no ice boa d pos ings and local ad e isemen s.
W i en in o med consen was ob ained om each pa ici-
pan . The s udy p o ocol was app o ed by he medical e hics
commi ee o he Ch is ian-Alb ech s-Uni e si y o Kiel, Ge -
many, and ollowed he guidelines based on he ‘Decla a ion
o Helsinki’. The p ima y aim o he s udy was o alida e mea-
su es o bioelec ical impedance analysis s. e e ence
me hods in olde adul s. The ial was egis e ed a
ClinicalT ials.go as NCT04028648. The s udy popula ion was
expanded by a subg oup o 40 heal hy Caucasian olde pa ic-
ipan s as desc ibed in de ail elsewhe e.
17
F om he included
190 pa icipan s, da a o 173 adul s we e analysed (da a om
15 pa icipan s we e excluded because o mo ion a e ac s o
inco ec pa ien posi ioning in MRI. Fu he da a om wo
subjec s we e excluded due o missing endoc ine pa ame e s).
Body composi ion analysis
Body weigh was measu ed o he nea es 0.01 kg by an elec-
onic Tani a scale (Tani a, Tokyo, Japan) coupled o he BOD
POD® Body Composi ion Sys em (Cosmed s l, Rome, I aly)
wi h subjec s in unde wea . Heigh was de e mined wi hou
shoes using a s adiome e (SECA, Modell 285, Hambu g,
Ge many). Fa mass (FM) and a - ee mass (FFM) we e de-
e mined ia ai -displacemen ple hysmog aphy (BOD POD®
Cosmed s l, Rome, I aly) as p e iously desc ibed.
18
FM was
calcula ed using he equa ion by Si i e al.
19
FFM was calcu-
la ed om he di e ence be ween body weigh and FM. On
he basis o FM and FFM, FM-Index (FMI) and FFM-Index
(FFMI) we e calcula ed as FM (kg)/heigh (m
2
) and FFM
(kg)/heigh (m
2
).
SM and AT we e measu ed using whole body MRI as de-
sc ibed in de ail elsewhe e.
20
B iefly, subjec s we e examined
in a supine posi ion wi h a ms ex ended abo e hei heads.
Fo scans in abdominal and ho acic egions pa icipan s we e
equi ed o hold hei b ea h. Images we e ob ained using a
1.5 T scanne (Magne om A an o, Siemens Medical Sys ems,
E langen, Ge many) wi h a T1-weigh ed-g adien echo
sequence ( epe i ion ime (TR): 157 ms; echo ime (TE):
4 ms o scans o a ms, legs and abdominal egion). The
whole body was scanned om w is o ankle using
con inuous axial images wi h a slice hickness o 8 mm and
2 mm in e slice gaps o a ms, legs and unk. Volumes o
SM, subcu aneous adipose issue (SAT) and isce al adipose
issue (VAT) we e manually segmen ed using SliceOma ic
4.3 so wa e (Tomo ision, Mon eal, Canada). VAT was e alu-
a ed om he op o he li e o emo al heads. Volumes o
o al SM (excluding head and neck muscles, hands and ee ),
SAT and VAT we e de e mined om he sum o issue a eas
(cm
2
) mul iplied by he slice hickness. Tissue olumes we e
hen con e ed in o masses using he assumed densi ies o
1.04 g cm
3
o SM and 0.92 g cm
3
o SAT and VAT.
21
SM
was no malized o heigh squa ed o calcula e skele al mus-
cle mass index (SMI, (kg)/heigh (m
2
)).
In a subg oup o 135 subjec s, whole body bone mine al
con en (BMC), BMD and T-Sco e we e quan ified using
dual ene gy X- ay abso p iome y (DXA) (HOLOGIC Disco e y
Analysis o he adiponec in pa adox in heal hy olde people 271
Jou nal o Cachexia, Sa copenia and Muscle 2023; 14: 270–278
DOI: 10.1002/jcsm.13127
1353921906009, 2023, 1, Downloaded om h ps://onlinelib a y.wiley.com/doi/10.1002/jcsm.13127 by Uni e si a sbiblio hek Kiel, Wiley Online Lib a y on [18/08/2023]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
A (S/N 82686), Inc., Bed o d, MA, USA). Be o e daily measu e-
men s, a spine phan om calib a ion was pe o med. Scans
we e analysed using manu ac u e ’s so wa e ( e sion
12.6.1:3, Hologic, Inc.). Resul s we e summed up o bo h
a ms and legs as well as he head.
Li e a was de e mined by MRI (Magne om A an o, Sie-
mens Medical Sys ems, E langen, Ge many) based on he
wo-poin Dixon me hod wi h a olume ic in e pola ed
b ea h-hold examina ion sequence as desc ibed in de ail
elsewhe e.
22
B iefly, a T1-weigh ed g adien -echo sequence
wi h in-phase and ou -o -phase imaging was conduc ed (TR:
10.4 ms; TE: 4.76 (in-phase) and 7.14 (opposed-phase) ms;
flip angle, 10° ma ix, 80 × 128; and field o iew, 440 mm;
slice hickness/in e slice gap: 5/1 mm; o al scan ime:
19 s). F om in-phase and opposed-phase images, he wa e -
only (WO) and a -only (FO)-images we e calcula ed:
WO:1
2in-phase þopposed-phaseðÞ(1)
FO:1
2in-phase þopposed-phaseðÞ(2)
WO and FO-images we e han analysed using ImageJ so -
wa e (US NIH, Be hesda, MD, USA
22
) o de e mine hepa ic
a ac ion (HFF). In each o fi e adjacen HFF images, a sin-
gle con inuous egion o in e es (ROI) was defined
(20.62 × 20.62) and was placed in he li e pa enchyma,
a oiding ascula s uc u es. The quan i y o li e a was a -
e aged o he fi e HFF images and was de e mined as pe -
cen age o he o al li e co e.
In e muscula adipose issue (IMAT) in a single mid- high
MRI slice and muscle a by he wo-poin Dixon me hod
we e used o assess muscle quali y in 173 and 172 subjec s,
espec i ely (Figu es 1and 2).
IMAT was defined as isible AT be ween muscle g oups
ha is loca ed wi hin a muscle and benea h he muscle as-
cia. I was assessed in single c oss-sec ional MRI images a
he le el o he mid- high. The midpoin o he high was de-
fined as hal way be ween he emo al head and he ibial
pla eau. Masses o IMAT we e manually de e mined by using
a semi-au oma ic segmen a ion so wa e (SliceOma ic 4.3,
Tomo ision, Mon eal, Canada).
Muscle a was de e mined based on he Dixon me hod
using ImageJ so wa e (US NIH, Be hesda, MD, USA
22
). In
lumba egion o mul ifidus and e ec o spinae muscles, a sin-
gle con inuous ROI was defined (10.75 × 10.75) in each o fi e
adjacen muscle a ac ion images and was placed in he
same a ea o all epea ed measu emen s. Muscle a was
quan ified as pe cen age o he o al muscle a ea and was a -
e aged o he fi e muscle a ac ion images. All p ocedu es
we e conduc ed by he same obse e .
In 173 subjec s, hand g ip s eng h (HGS) was measu ed
using a hyd aulic SAEHAN® handg ip dynamome e (SH5001,
Masan, Sou h Ko ea). 135 subjec s conduc ed he es in a
s anding posi ion and 38 in a si ing posi ion and he elbow
was flexed a 90 deg ees wi h he shoulde a ached o he
o so. In 135 subjec s, HGS o he le and igh hand was
de e mined h ee imes and he g ea es alue o he
dominan hand was included in he analysis, whe eas in 38
subjec s, HGS was de e mined only wice.
Endoc ine pa ame e s
Se um and plasma blood samples we e aken om an
an ecubi al ein a e >10 h o e nigh as . The subjec s
we e ins uc ed o e ain om igo ous exe cise and alcohol
in ake o 24 h p io o blood sampling. A e collec ion, se-
Figu e 1 In e muscula adipose issue (IMAT) in a single mid- high magne ic esonance imaging (MRI) slice segmen ed in pu ple using SliceOma ic
so wa e, acqui ed as axial T1-weigh ed g adien -echo sequence. Resul o o al IMAT was 9.30 g.
272 C.O. Walowski e al.
Jou nal o Cachexia, Sa copenia and Muscle 2023; 14: 270–278
DOI: 10.1002/jcsm.13127
1353921906009, 2023, 1, Downloaded om h ps://onlinelib a y.wiley.com/doi/10.1002/jcsm.13127 by Uni e si a sbiblio hek Kiel, Wiley Online Lib a y on [18/08/2023]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
um samples we e s o ed a oom empe a u e in an up igh
posi ion o 30 min o comple e clo o ma ion. Plasma and
se um we e ob ained by cen i uga ion a 2000 g o
10 min a 20°C and s o ed a 40°C. Sample analyses we e
pe o med a he ‘Ge man Ins i u e o Human Nu i ion’,
Po sdam-Rehb ücke, Depa men o Nu i ion and Ge on ol-
ogy, Nu he al, Ge many and a labo a o y in Kiel, Ge many.
In 172 subjec s, lep in (in a-assay CV: 4.2–7.6%,
in e -assay CV: 4.4–6.7%; BioVendo , B no, Czech Republic),
adiponec in (in a-assay CV: 2.8–3.9%, in e -assay CV: 5.9–
6.4%; Immundiagnos ik AG, Bensheim, Ge many) as well as
insulin-like g ow h ac o 1 (IGF-1) (in a-assay CV: 5.1–
6.7%, in e -assay CV: 5.5–6.6%; BioVendo , B no, Czech
Republic) we e measu ed by comme cial ELISA ki s. As adipo-
nec in exp ession is egula ed by he hepa ic ho mone fib o-
blas g ow h ac o 21 (FGF-21), also FGF-21 concen a ions
we e quan ified by ELISA (in a-assay CV: 1.6–2.4%,
in e -assay CV: 3.1–3.5%; BioVendo , B no, Czech Republic)
in a subg oup o 135 subjec s. As inflamma o y pa ame e s,
in e leukin 6 (IL-6) (in a-assay CV: 4.2–5.1%, in e -assay CV:
4.7–5.0%; BioVendo , B no, Czech Republic) was de e mined
in 135 pa icipan s using comme cial ELISA ki , and high-sen-
si i i y C- eac i e p o ein (hsCRP) (in a-assay CV: 0.73–
5.73%, in e -assay CV: 1.50–5.76%; BECKMAN COULTER,
B ea, CA, USA) was measu ed using an
immuno- u bidime ic es . Insulin was de e mined by chemi-
luminescen mic opa icle immunoassay (in a-assay CV: 1.4–
2.1%, in e -assay CV: 1.5–2.2%; Abbo , Wiesbaden,
Ge many). Inflamma ion was based on hsCRP >3 mg/L and
ele a ed insulin le els we e se a >25.0 mU/L.
S a is ical analysis
S a is ical analyses we e pe o med using SPSS s a is ical so -
wa e (SPSS 28.0, Inc., Chicago, IL, USA). All da a a e gi en as
means ±SD. Di e ences be ween independen samples we e
analysed using unpai ed - es . E alua ion o no mali y was
pe o med using he Shapi o–Wilk es and esidual analysis.
Pea son’s and Spea man’s co ela ion coe ficien s we e calcu-
la ed o iden i y bi a ia e associa ions be ween and wi hin
body composi ion, endoc ine and unc ional pa ame e s. Pa -
ial co ela ions we e used o adjus o a ious con ounde s.
S epwise mul iple eg ession analyses we e pe o med o as-
sess ac o s independen ly associa ed wi h SMI, BMC and
lumba muscle a . All es s we e wo-sided and le el o sig-
nificance was se a P<0.05.
Resul s
In o al, 173 olde adul s (101 women and 72 men) aged 59–
86 yea s wi h a BMI be ween 18 and 37 kg/m
2
we e included
in he s udy. Desc ip i e cha ac e is ics a e summa ized in
Table 1. Men we e significan ly olde and had a highe BMI,
FFMI, SM, SMI, IMAT, VAT, HGS as well as BMC, BMD and
T-Sco e compa ed wi h women. Acco ding o WHO c i e ia,
26.6% o women and 30.6% o men we e o e weigh o
obese. In a subpopula ion o 135 subjec s wi h DXA esul s,
he p e alence o a educed muscle mass was 7.40% acco d-
ing o he ecommended FFMI h esholds o he ‘Global Lead-
e ship Ini ia i e on Malnu i ion’(FFMI cu -o s: <15 and
<17 kg/m
2
in women and men, espec i ely
23
).
Po en ial endoc ine de e minan s o adiponec in le els a e
summa ized in Table 2. Adiponec in le els we e lowe in men
compa ed wi h women. Insulin and IGF-1 le els we e highe
and lep in le els we e lowe in men compa ed wi h women.
P e alence o ele a ed hsCRP and insulin le els we e 20.2%
and 2.3%, espec i ely.
Co ela ions be ween adiponec in o IGF-1 le els and
body composi ion pa ame e s a e p esen ed in Table 3.In
Figu e 2 Lumba muscle a in he egion o mul ifidus and e ec o spinae muscles wi h a yellow 10.75 × 10.75 egion o in e es (ROI) de e mined
using ImageJ so wa e, acqui ed as axial T1-weigh ed g adien -echo Dixon sequence. Resul o he pe cen age o muscle a was 9.54%.
Analysis o he adiponec in pa adox in heal hy olde people 273
Jou nal o Cachexia, Sa copenia and Muscle 2023; 14: 270–278
DOI: 10.1002/jcsm.13127
1353921906009, 2023, 1, Downloaded om h ps://onlinelib a y.wiley.com/doi/10.1002/jcsm.13127 by Uni e si a sbiblio hek Kiel, Wiley Online Lib a y on [18/08/2023]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
acco dance wi h he adiponec in pa adox, highe adiponec in
le els we e associa ed wi h a lowe SMI and BMC in he o al
s udy popula ion. No co ela ion was obse ed be ween adi-
ponec in and HGS. Lowe adiponec in le els we e associa ed
wi h a highe BMI ( =0.34, P<0.01) and FMI in men and
wi h g ea e VAT in he o al popula ion. The associa ion be-
ween adiponec in and SMI emained significan a e adjus -
men o VAT ( =0.16, P<0.04). No ela ionships be ween
adiponec in and FGF-21, lep in, IL-6 o hsCRP and insulin we e
ound.
In con as o adiponec in, IGF-1 le els we e posi i ely as-
socia ed wi h SMI in he o al popula ion and in he sub-
g oups o men and women. Fu he mo e, IGF-1 concen a-
ions we e co ela ed wi h BMC, BMD and T-Sco e in he
o al popula ion and BMD and T-Sco e in women. IGF-1 le els
we e also posi i ely associa ed wi h HGS ( = 0.31, P<0.05,
all; = 0.35, P<0.01, men) and nega i ely wi h age
( =0.21, P<0.01, all; =0.20, P<0.05, women;
=0.33, P<0.01, men) and adiponec in le els
( =0.15, P<0.05). To es , i he pa adoxical associa ion
be ween highe adiponec in and lowe SMI could be ex-
plained by lowe IGF-1 le els wi h highe age, pa ial co ela-
ion analysis be ween adiponec in and SMI adjus ed o IGF-1
was pe o med. The nega i e co ela ion be ween SMI and
adiponec in in he o al s udy popula ion pe sis ed, bu was
sligh ly weakened ( =0.20, P= 0.01).
S epwise eg ession analyses wi h SMI o BMC as depen-
den a iables and adiponec in, IGF-1, insulin, IL-6, hsCRP,
lep in and age ( o SMI) and adiponec in, IGF-1, IL-6, lep in
and age ( o BMC), espec i ely as independen a iables
we e pe o med (Table 4). Insulin, IGF-1 and lep in explained
18.4% o he a iance in SMI. A e conside ing sex as u he
Table 1 Cha ac e is ics o he s udy popula ion
All subjec s Women Men
n173 101 72
Age (yea s) 70.7 ± 5.3 70.0 ± 4.9* 71.7 ± 5.7
Heigh (m) 1.68 ± 0.10 1.62 ± 0.06*** 1.77 ± 0.1
Weigh (kg) 73.3 ± 15.2 65.1 ± 11.0*** 84.7 ± 12.7
BMI (kg/m
2
) 25.7 ± 3.8 24.9 ± 4.0*** 27.0 ± 3.2
FMI (kg/m
2
) 9.2 ± 3.4 9.9 ± 3.6*** 8.1 ± 2.7
SAT (kg) 17.4 ± 6.5 18.8 ± 6.8*** 15.5 ± 5.5
VAT (kg) 2.2 ± 1.6 1.4 ± 0.9*** 3.3 ± 1.7
FFMI (kg/m
2
) 16.6 ± 2.3 15.0 ± 1.2*** 18.8 ± 1.2
SM (kg) 22.2 ± 5.9 18.0 ± 2.5*** 28.0 ± 4.1
SMI (kg/m
2
) 7.7 ± 1.4 6.9 ± 0.8*** 8.9 ± 1.1
BMC (kg) 2.07 ± 0.54 1.71 ± 0.27*** 2.61 ± 0.35
BMD (g/cm
2
) 1.00 ± 0.14 0.92 ± 0.10*** 1.12 ± 0.10
T-Sco e 1.5 ± 1.2 2.1 ± 1.1*** 0.7 ± 1.0
Li e a (%) 8.4 ± 4.2 8.1 ± 4.5 8.8 ± 3.8
Lumba muscle a (%) 9.5 ± 3.7 9.3 ± 3.8 9.6 ± 3.7
IMAT single mid- high (g) 4.5 ± 2.3 3.4 ± 2.1*** 5.4 ± 2.3
HGS (kg) 31.9 ± 10.3 25.0 ± 5.0*** 41.4 ± 7.9
Abb e ia ions: BMC, bone mine al con en ; BMD, bone mine al densi y; BMI, body mass index; FFMI, a - ee mass index; FMI, a mass
index; HGS, hand g ip s eng h; IMAT, in e muscula adipose issue; SAT, subcu aneous adipose issue; SM, skele al muscle; SMI, skele al
muscle mass index; VAT, isce al adipose issue.
No e: Values a e means ± SD; n, no. o subjec s.
*
P<0.05.
***
P<0.001 sex di e ences by - es , wo-sided.
Table 2 Adiponec in le els and i s po en ial endoc ine de e minan s
All subjec s Women Men
n173 101 72
Adiponec in (mg/L) 19.8 ± 16.4 22.8 ± 19.3** 15.5 ± 9.8
IGF-1 (μg/L) 151.3 ± 56.8 140.3 ± 52.5** 166.7 ± 59.4
FGF-21 (pg/mL) 212.2 ± 212.2 233.5 ± 255.3 180.3 ± 117.3
Lep in (ng/mL) 11.2 ± 11.0 14.2 ± 12.7*** 6.6 ± 5.5
IL-6 (pg/mL) 10.11 ± 24.52 6.72 ± 6.47 15.20 ± 37.58
hsCRP (mg/L) 2.31 ± 3.07 2.12 ± 2.60 2.58 ± 3.63
Insulin (μU/L) 9.8 ± 6.1 8.9 ± 4.3* 10.9 ± 7.8
Abb e ia ions: FGF-21, fib oblas g ow h ac o 21; hsCRP, high-sensi i i y C- eac i e p o ein; IGF-1, insulin-like g ow h ac o 1; IL-6, in-
e leukin 6.
No e: Values a e means ± SD; n, no. o subjec s.
*
P<0.05.
**
P<0.01.
***
P<0.001 sex di e ences by - es , wo-sided.
274 C.O. Walowski e al.
Jou nal o Cachexia, Sa copenia and Muscle 2023; 14: 270–278
DOI: 10.1002/jcsm.13127
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co a ia e, sex and insulin oge he explained 65.1% o he
a iance in SMI. IGF-1, lep in and age explained 16.4% o
he a iance in BMC. A e addi ional adjus men o sex, only
sex was en e ed in he equa ion and explained 68.5% o he
a iance in BMC.
A e excluding subjec s wi h ele a ed hsCRP le els,
he nega i e associa ion be ween adiponec in concen a-
ions and BMC in he o al popula ion was no longe signi -
ican (P= 0.08), whe eas nega i e co ela ions be ween
adiponec in le els and insulin ( =0.18, P<0.05), BMI
( =0.18, P<0.05) and HGS ( =0.18, P<0.05)
could be obse ed. The nega i e associa ion be ween
IGF-1 and adiponec in le els in he o al popula ion
pe sis ed ( =0.18, P<0.05).
Conce ning ec opic a , highe adiponec in le els we e as-
socia ed wi h lowe li e a in he o al s udy popula ion
and in he subg oup o men, whe eas adiponec in le els
we e pa adoxically posi i ely co ela ed wi h lumba muscle
a in women (Table 3). By con as , IGF-1 showed nega i e
co ela ions wi h lumba muscle a in women and in he
o al s udy popula ion. The nega i e associa ion be ween
adiponec in and lumba muscle a in women weakened
a e adjus men o IGF-1 ( = 0.19, P= 0.05). S epwise e-
g ession analysis wi h lumba muscle a as he dependen
a iable and adiponec in, IGF-1, lep in, insulin, IL-6, hsCRP,
FMI and age as independen a iables, e ealed ha only
FMI and IGF-1 independen ly explained 34.3% o he a i-
ance (Table 4).
Insulin, lep in, IL-6 and hsCRP we e posi i ely co ela ed
wi h ec opic a deposi ion in li e and muscle, whe eas
highe FGF-21 le els we e posi i ely co ela ed wi h li e a
con en . Fu he mo e, ec opic li e and muscle a showed
consis en posi i e associa ions wi h FMI and VAT anging be-
ween = 0.31 and = 0.61 (all P<0.05).
Table 3 Co ela ions be ween adiponec in o IGF-1 and body composi ion pa ame e s
All subjec s Women Men
Adiponec in (mg/L) IGF-1 (μg/L) Adiponec in (mg/L) IGF-1 (μg/L) Adiponec in (mg/L) IGF-1 (μg/L)
SMI (kg/m
2
)0.23** 0.33** - 0.22* - 0.39**
BMC (kg) 0.17* 0.33** ----
BMD (g/cm
2
) - 0.37** - 0.22* - -
T-Sco e - 0.34** - 0.22* - -
FMI (kg/m
2
) ----0.32** -
VAT (kg) 0.21** -----
Li e a (%) 0.20* - - - 0.26* -
Lumba muscle a (%) - 0.17* 0.27** 0.30** - -
IMAT single mid- high (g) ------
Abb e ia ions: BMC, bone mine al con en ; BMD, bone mine al densi y; FMI, a mass index; IGF-1, insulin-like g ow h ac o 1; IMAT,
in e muscula adipose issue; SMI, skele al muscle mass index; VAT, isce al adipose issue.
*
P<0.05.
**
P<0.01.
Table 4 S epwise mul iple eg ession analyses wi h SMI, BMC and lumba muscle a as dependen a iables
Dependen a iables and p edic o s βcoe ficien R
2
SEE P- alue VIF
SMI (kg/m
2
)
Model
a
S ep 1: insulin (μU/L) 0.073 0.101 0.018 <0.001 1.135
S ep 2: IGF-1 (μg/L) 0.005 0.150 0.002 0.015 1.053
S ep 3: lep in (ng/mL) 0.023 0.184 0.010 0.021 1.104
BMC (kg)
Model
b
S ep 1: IGF-1 (μg/L) 3.232 0.098 0.794 <0.001 1.044
S ep 2: lep in (ng/mL) 8.500 0.135 3.715 0.024 1.009
S ep 3: age (y) 16.918 0.164 7.949 0.035 1.040
Lumba muscle a (%)
Model
c
S ep 1: FMI (kg/m
2
) 0.56 0.296 0.100 0.100 1.020
S ep 2: IGF-1 (μg/L) 0.02 0.343 0.007 0.007 1.020
Abb e ia ions: BMC, bone mine al con en ; FMI, a mass index; IGF-1, insulin-like g ow h ac o 1; SEE, s anda d e o o es ima ion; SMI,
skele al muscle mass index; VIF, a iance infla ion ac o .
a
Model: independen a iables: adiponec in, IGF-1, insulin, IL-6, hsCRP, lep in and age.
b
Model: independen a iables: adiponec in, IGF-1, lep in, IL-6 and age.
c
Model: independen a iables: adiponec in, IGF-1, lep in, insulin, IL-6, hsCRP, FMI and age.
Analysis o he adiponec in pa adox in heal hy olde people 275
Jou nal o Cachexia, Sa copenia and Muscle 2023; 14: 270–278
DOI: 10.1002/jcsm.13127
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Discussion
Ou da a confi m he adiponec in pa adox in olde adul s
wi hou inflamma o y diseases. Highe adiponec in le els
we e associa ed wi h lowe SMI and BMC in he o al s udy
popula ion and highe lumba muscle a in women. These
obse a ions may explain he posi i e associa ion be ween
adiponec in and mo ali y ha was ound in p e ious s udies
e en independen o como bid condi ions like his o y o
cance ,
8
hype ension, diabe es, ca dio ascula disease, con-
ges i e hea ailu e
8,24
and ch onic kidney disease.
24
Howe e , adiponec in may no be causally ela ed o an
unheal hy body composi ion because o he nega i e associ-
a ion be ween adiponec in and IGF-1. IGF-1 has well-known
anabolic e ec s on muscle and bone ( o a e iew, see
Goma asca e al.
25
). In line wi h ou hypo hesis, s epwise
mul iple eg ession analyses e ealed ha adiponec in was
no significan p edic o o SMI, BMC and lumba muscle a
when conside ing IGF-1 as a dependen a iable (Table 4).
Simila o ou esul s in heal hy people, adiponec in le els
we e nega i ely ela ed o se um IGF-1 in ac omegaly
26
as
well as in men wi h ype 2 diabe es.
27
This co ela ion was
independen o BMI,
26,27
enal unc ion and age,
27
sugges ing
ha IGF-1 migh inhibi he exp ession o adiponec in. In
i o expe imen s in cul u ed 3T3-L1 adipocy es ha e indeed
shown dec eased adiponec in mRNA le els by IGF-1 o
insulin
28
and a s udy in a s demons a ed ha in usion o
ecombinan human IGF-1 dec eased plasma le els o
adiponec in.
29
By con as , IGF-1 supplemen a ion in pa ien s
wi h g ow h ho mone deficiency did no a ec se um adipo-
nec in le els.
30
In ou s udy, IGF-1 le els we e nega i ely co ela ed wi h
age and may he e o e explain highe adiponec in le els in
an olde popula ion. The nega i e associa ion be ween adipo-
nec in and IGF-1 in pa ien s wi h ype 2 diabe es
27
may be
due o impai ed insulin sec e ion and hus lowe IGF-1 le els
in hese pa ien s,
31
whe eas in pa ien s wi h ac omegaly,
o e p oduc ion o IGF-1 may con ibu e o lowe adiponec in
concen a ions. The e was a lack o associa ion be ween adi-
ponec in and IGF-1 le els in pa ien s wi h mo bid obesi y a -
e weigh loss induced by ba ia ic su ge y
32
whe eas in
young women wi h non-diabe ic obesi y a posi i e associa-
ion be ween IGF-1 and adiponec in was ound.
33
In he la e
s udy, a significan nega i e co ela ion be ween IGF-1 and
CRP was obse ed indica ing ha inflamma ion may be
causal o he posi i e associa ion be ween IGF-1 and adipo-
nec in because inflamma ion may impai he exp ession o
bo h ho mones
33–35
( o a e iew, see Ki k e al.
36
).
In con as o he associa ion be ween IGF-1 and muscle
mass, muscle a o bone mass, o he bes o ou knowledge
he e is no di ec causal e ec o IGF-1 on VAT o li e a .
The e o e, he plausible nega i e co ela ions be ween adipo-
nec in and VAT ( o al popula ion), FMI and li e a (especially
in men) we e e iden in ou hea hy olde popula ion (Table 3).
An al e na i e explana ion o he adiponec in pa adox is
ha highe adiponec in le els in people wi h a lowe SM
may be in e p e ed as a s a a ion signal (i.e. as a conse-
quence o poo nu i ional s a us
37
o his o y o weigh loss
among olde people
8
). In line wi h his a gumen , weigh loss
leads o an inc ease in adiponec in le els no only in people
wi h obesi y
32
bu also in heal hy lean subjec s.
38
In he p es-
en s udy, pa ial co ela ion be ween adiponec in and SMI
adjus ed o IGF-1 e ealed, ha he nega i e co ela ion
be ween SMI and adiponec in was only sligh ly weakened.
Because ou da a a e c oss-sec ional, we canno exclude he
possibili y ha a low SMI is causal o highe adiponec in
le els. Adiponec in is also sec e ed by myocy es, he e o e
he impac o ene gy a ailabili y on his e ec needs o be
in es iga ed. The in e p e a ion o highe adiponec in le els
as a s a a ion signal is howe e unlikely in a heal hy
non-malnou ished s udy popula ion o communi y-dwelling
olde people.
The p esen s udy has se e al s eng hs. Fi s , he sample
o olde communi y-dwelling Caucasians was heal hy, hus
con ounde s caused by disease can be excluded. In addi ion,
he popula ion was well cha ac e ized using whole body MRI,
which is conside ed as he gold s anda d me hod o
assessmen o SM and muscle a . Body composi ion was
complemen ed wi h HGS as a unc ional pa ame e . Ne e -
heless, ou findings should be conside ed in he con ex o
some limi a ions. Fi s , adiponec in ci cula es in blood in mul-
iple iso o ms wi h di e en physiologic unc ions.
39,40
As
only o al adiponec in concen a ions we e measu ed, he e -
ec s o he di e en iso o ms canno be examined. Finally,
ou esul s need o be confi med using a longi udinal s udy
design. Fo example, nu i ion in e en ions migh a ec ad-
iponec in le els media ed by IGF-1. I has been demons a ed
ha IGF-1 le els dec ease in esponse o as ing and
sho - e m calo ic es ic ion o p o ein es ic ion
41
( o a e-
iew, see Thissen e al.
42
). The e ec o p o ein supplemen a-
ion in heal hy olde people on adiponec in le els emains o
be in es iga ed.
In conclusion, ou esul s sugges ha adiponec in is no
causally ela ed o impai ed mass and unc ion o he
musculoskele al sys em in heal hy olde people bu he as-
socia ions a e media ed by an age- ela ed decline in IGF-1
le els ha con ibu e o an inc ease in adiponec in. These
esul s suppo he hypo hesis o a unc ional in e play
be ween IGF-1 and adiponec in ha had been p oposed
by O ù e al.
43
Acknowledgemen s
The s udy p o ocol was app o ed by he medical e hics com-
mi ee o he Ch is ian-Alb ech s-Uni e si y o Kiel, Ge many,
and ollowed he guidelines based on he ‘Decla a ion o Hel-
276 C.O. Walowski e al.
Jou nal o Cachexia, Sa copenia and Muscle 2023; 14: 270–278
DOI: 10.1002/jcsm.13127
1353921906009, 2023, 1, Downloaded om h ps://onlinelib a y.wiley.com/doi/10.1002/jcsm.13127 by Uni e si a sbiblio hek Kiel, Wiley Online Lib a y on [18/08/2023]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
sinki’. W i en in o med consen was ob ained om each pa -
icipan . The au ho s ce i y ha hey comply wi h he e hical
guidelines o au ho ship and publishing in he Jou nal o Ca-
chexia, Sa copenia and Muscle.
44
This wo k was suppo ed by
a g an o seca gmbh & co.kg., Ge many (2019/2020) and he
Danone Ins i u e-Nu i ion o Heal h, Ge many (2013/14).
We hank B i a Jux and he Clinic o Diagnos ic Radiology,
Uni e si y medical Cen e Schleswig-Hols ein, Kiel (Ge many)
o he help wi h MRI scanning.
Open Access unding enabled and o ganized by P ojek
DEAL.
Conflic o in e es
Anja Bosy-Wes phal se es a consul an o seca gmbh & co.
kg. The o he au ho s decla e no conflic o in e es .
Re e ences
1. Fazeli PK, Ho owi z MC, MacDougald OA,
Schelle EL, Rodehe e MS, Rosen CJ, e
al. Ma ow a and bone--new pe spec-
i es. J Clin Endoc inol Me ab 2013;98:
935–945.
2. Robinson K, P ins J, Venka esh B. Clinical
e iew: Adiponec in biology and i s ole in
inflamma ion and c i ical illness. C i Ca e
2011;15:221.
3. Di Chia a T, A gano C, Co ao S, Scaglione R,
Lica a G. Hypoadiponec inemia: A Link be-
ween Visce al Obesi y and Me abolic Syn-
d ome. J Nu Me ab 2012;2012:175245.
4. Hui E, Xu A, Chow W-S, Lee PCH, Fong CHY,
Cheung SCW, e al. Hypoadiponec inemia
as an independen p edic o o he p o-
g ession o ca o id a he oscle osis: A
5-yea p ospec i e s udy. Me ab Synd
Rela Diso d 2014;12:517–522.
5. Engl J, S u m W, Sandho e A, Kase S,
Tschone A, Ta a czyk T, e al. E ec o p o-
nounced weigh loss on isce al a , li e
s ea osis and adiponec in iso o ms. Eu J
Clin In es 2008;38:238–244.
6. Gambe i T, Maghe ini F, Fiaschi T. Adipo-
nec in in Myopa hies. In J Mol Sci 2019;
20:1544.
7. Lewis JW, Edwa ds JR, Naylo AJ,
McGe ick HM. Adiponec in signalling in
bone homeos asis, wi h age and in disease.
Bone Res 2021;9:1.
8. Bake JF, Newman AB, Kanaya A, Leona d
MB, Zemel B, Miljko ic I, e al. The Adipo-
nec in Pa adox in he Elde ly: Associa ions
Wi h Body Composi ion, Physical Func ion-
ing, and Mo ali y. J Ge on ol A Biol Sci
Med Sci 2019;74:247–253.
9. Michaëlsson K, Lind L, F ys yk J, Fly bje g
A, Gedebo g R, Be ne C, e al. Se um adi-
ponec in in elde ly men does no co ela e
wi h ac u e isk. J Clin Endoc inol Me ab
2008;93:4041–4047.
10. Oba a Y, Yamada Y, Takahi Y, Baden MY,
Saisho K, Tamba S, e al. Rela ionship be-
ween se um adiponec in le els and age
in heal hy subjec s and pa ien s wi h ype
2 diabe es. Clin Endoc inol (Ox ) 2013;79:
204–210.
11. Menzaghi C, T ischi a V. The Adiponec in
Pa adox o All-Cause and Ca dio ascula
Mo ali y. Diabe es 2018;67:12–22.
12. Ue ani E, Taba a Y, Kawamo o R, Onuma H,
Koha a K, Osawa H, e al. CDH13 Geno-
ype–Dependen Associa ion o High–Mo-
lecula Weigh Adiponec in Wi h All-Cause
Mo ali y: The J-SHIPP S udy. Diabe es Ca e
2014;37:396–401.
13. Kalkman HO. An Explana ion o he Adipo-
nec in Pa adox. Pha maceu icals (Basel)
2021;14:1266.
14. Sa a N, Nelson SM. Adiponec in, Diabe-
es, and Co ona y Hea Disease in Olde
Pe sons: Un a eling he Pa adox. J Clin
Endoc inol Me ab 2008;93:3299–3301.
15. Szabó T, Sche bako N, Sandek A, Kung T,
on Haehling S, Lainscak M, e al. Plasma
adiponec in in hea ailu e wi h and wi h-
ou cachexia: Ca abolic signal linking
ca abolism, symp oma ic s a us, and p og-
nosis. Nu Me ab Ca dio asc Dis 2014;24:
50–56.
16. Bake JF, on Feld JM, Mos oufi-Moab S,
Kim W, Ta a u a E, Leona d MB. Insulin-like
G ow h Fac o 1 and Adiponec in and As-
socia ions wi h Muscle Defici s, Disease
Cha ac e is ics, and T ea men s in Rheu-
ma oid A h i is. J Rheuma ol 2015;42:
2038–2045.
17. Schwei ze L, Geisle C, Johannsen M, Glüe
C-C, Mülle MJ. Associa ions be ween body
composi ion, physical capabili ies and pul-
mona y unc ion in heal hy olde adul s.
Eu J Clin Nu 2017;71:389–394.
18. Bosy-Wes phal A, Mas M, Eichho n C,
Becke C, Ku zne D, Helle M, e al. Valida-
ion o ai -displacemen ple hysmog aphy
o es ima ion o body a mass in heal hy
elde ly subjec s. Eu J Nu 2003;42:
207–216.
19. Si i WE. Body composi ion om fluid
spaces and densi y: Analysis o me hods
1961. Nu i ion 1993;9:480–491.
20. Hübe s M, Geisle C, Plach a-Danielzik S,
Mülle MJ. Associa ion be ween indi idual
a depo s and ca dio-me abolic ai s in
no mal- and o e weigh child en, adoles-
cen s and adul s. Nu Diabe es 2017;7:
e267.
21. Snyde WS, Cook MJ, Nasse ES, Ka hausen
LR, Howells GP, Tip on IH. Repo o he
Task G oup on Re e ence Man. (ICRP 23).
Ox o d: Pe gamon P ess, 1975. Ann ICRP
1979;3:iii–iii.
22. Ma J. Dixon echniques o wa e and a
imaging. J Magn Reson Imaging 2008;28:
543–558.
23. Cede holm T, Jensen GL, Co eia MITD,
Gonzalez MC, Fukushima R, Higashiguchi
T, e al. GLIM c i e ia o he diagnosis o
malnu i ion –A consensus epo om
he global clinical nu i ion communi y. Clin
Nu 2019;38:1–9.
24. Poehls J, Wassel CL, Ha is TB, Ha el PJ,
Swa b ick MM, Cummings SR, e al.
Associa ion o adiponec in wi h mo ali y
in olde adul s: The Heal h, Aging, and
Body Composi ion S udy. Diabe ologia
2009;52:591–595.
25. Goma asca M, BanfiG, Lomba di G.
Myokines: The endoc ine coupling o skele-
al muscle and bone. Ad Clin Chem 2020;
94:155–218.
26. Fukuda I, Hizuka N, Ishikawa Y, I oh E,
Yasumo o K, Mu akami Y, e al. Se um adi-
ponec in le els in adul g ow h ho mone
deficiency and ac omegaly. G ow h Ho m
IGF Res 2004;14:449–454.
27. Kanazawa I, Yamaguchi T, Sugimo o T. Se-
um insulin-like g ow h ac o -I is nega-
i ely associa ed wi h se um adiponec in
in ype 2 diabe es melli us. G ow h Ho m
IGF Res 2011;21:268–271.
28. Lam KS-L, Xu A, Tan KC-B, Wong L-C, Tiu
S-C, Tam S. Se um adiponec in is educed
in ac omegaly and no malized a e co ec-
ion o g ow h ho mone excess. J Clin
Endoc inol Me ab 2004;89:5448–5453.
29. Yamaza H, Koma su T, To K, Toyama H,
Chiba T, Higami Y, e al. In ol emen o
Insulin-Like G ow h Fac o -1 in he E ec
o Calo ic Res ic ion: Regula ion o Plasma
Adiponec in and Lep in. J Ge on ol A Biol
Sci Med Sci 2007;62:27–33.
30. Schmid C, Bianda T, Zwimp e C, Zap J,
Wiesli P. Changes in insulin sensi i i y
induced by sho - e m g ow h ho mone
(GH) and insulin-like g ow h ac o I (IGF-I)
ea men in GH-deficien adul s a e no
associa ed wi h changes in adiponec in
le els. G ow h Ho m IGF Res 2005;15:
300–303.
31. Suda K, Ma sumo o R, Fukuoka H, Iguchi G,
Hi o a Y, Nishizawa H, e al. The influence
o ype 2 diabe es on se um GH and IGF-I
le els in hospi alized Japanese pa ien s.
G ow h Ho m IGF Res 2016;29:4–10.
32. Pa dina E, Fe e R, Baena-Fus egue as JA,
Lecube A, Fo JM, Va gas V, e al. The
ela ionships be ween IGF-1 and CRP, NO,
lep in, and adiponec in du ing weigh loss
in he mo bidly obese. Obes Su g 2010;
20:623–632.
33. Si bu A, Gologan S, A banas T, Copaescu C,
Ma in S, Albu A, e al. Adiponec in, body
mass index and hepa ic s ea osis a e inde-
Analysis o he adiponec in pa adox in heal hy olde people 277
Jou nal o Cachexia, Sa copenia and Muscle 2023; 14: 270–278
DOI: 10.1002/jcsm.13127
1353921906009, 2023, 1, Downloaded om h ps://onlinelib a y.wiley.com/doi/10.1002/jcsm.13127 by Uni e si a sbiblio hek Kiel, Wiley Online Lib a y on [18/08/2023]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
penden ly associa ed wi h IGF-I s a us in
obese non-diabe ic women. G ow h Ho m
IGF Res 2013;23:2–7.
34. Sa as ano S, Di Somma C, Pizza G, de Rosa
A, Nedi V, Rossi A, e al. Li e -spleen axis,
insulin-like g ow h ac o -(IGF)-I axis and
a mass in o e weigh /obese emales. J
T ansl Med 2011;9:136.
35. Ouchi N, Kiha a S, Funahashi T, Nakamu a
T, Nishida M, Kumada M, e al. Recip ocal
associa ion o C- eac i e p o ein wi h
adiponec in in blood s eam and adipose
issue. Ci cula ion 2003;107:671–674.
36. Ki k B, Feehan J, Lomba di G, Duque G.
Muscle, Bone, and Fa C oss alk: The Bio-
logical Role o Myokines, Os eokines, and
Adipokines. Cu Os eopo os Rep 2020;18:
388–400.
37. Hyun YY, Lee K-B, Oh K-H, Ahn C, Pa k SK,
Chae DW, e al. Se um adiponec in and
p o ein-ene gy was ing in p edialysis
ch onic kidney disease. Nu i ion 2017;33:
254–260.
38. Mülle MJ, Ende le J, Pou hassan M, B aun
W, Eggeling B, Lage pusch M, e al.
Me abolic adap a ion o calo ic es ic ion
and subsequen e eeding: The Minneso a
S a a ion Expe imen e isi ed. Am J Clin
Nu 2015;102:807–819.
39. Waki H, Yamauchi T, Kamon J, I o Y, Uchida
S, Ki a S, e al. Impai ed mul ime iza ion o
human adiponec in mu an s associa ed
wi h diabe es. Molecula s uc u e and
mul ime o ma ion o adiponec in. J Biol
Chem 2003;278:40352–40363.
40. Sche e PE, Williams S, Fogliano M, Baldini
G, Lodish HF. A No el Se um P o ein
Simila o C1q, P oduced Exclusi ely in
Adipocy es. J Biol Chem 1995;270:
26746–26749.
41. Smi h WJ, Unde wood LE, Clemmons DR.
E ec s o calo ic o p o ein es ic ion
on insulin-like g ow h ac o -I (IGF-I)
and IGF-binding p o eins in child en and
adul s. J Clin Endoc inol Me ab 1995;80:
443–449.
42. Thissen JP, Ke elslege s JM, Unde wood LE.
Nu i ional egula ion o he insulin-like
g ow h ac o s. Endoc Re 1994;15:
80–101.
43. O ù S, Nig o E, Mandola A, Alfie i A,
Buono P, Daniele A, e al. A Func ional In-
e play be ween IGF-1 and Adiponec in.
In J Mol Sci 2017;18:2145.
44. on Haehling S, Coa s AJS, Anke SD.
E hical guidelines o publishing in he
Jou nal o Cachexia, Sa copenia and Mus-
cle: Upda e 2021. J Cachexia Sa copenia
Muscle 2021;12:2259–2261.
278 C.O. Walowski e al.
Jou nal o Cachexia, Sa copenia and Muscle 2023; 14: 270–278
DOI: 10.1002/jcsm.13127
1353921906009, 2023, 1, Downloaded om h ps://onlinelib a y.wiley.com/doi/10.1002/jcsm.13127 by Uni e si a sbiblio hek Kiel, Wiley Online Lib a y on [18/08/2023]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License