Influence of body adiposity on structural characteristics of skeletal muscle in men and women

Influence of body adiposity on structural characteristicsof skeletal muscle in men and womenClaudio L. Lafortuna, Daniele Tresoldi and Giovanna Rizzo

Istituto di Bioimmagini e Fisiologia Molecolare del Consiglio Nazionale delle Ricerche, Segrate, Milan, Italy

Summary

CorrespondenceClaudio L. Lafortuna, Istituito di Bioimmagini

e Fisiologia Molecolare del C.N.R., via Cervi,

93, I-20090 Segrate, Milan, Italy

E-mail: [email protected]

Accepted for publicationReceived 10 April 2013;

accepted 31 May 2013

Key words

ageing; computed tomography imaging; muscle

quality; muscle quantity; overweight and obesity

The structure of skeletal muscle (SM) can be characterized by quantitative (size) andqualitative (composition) attributes, which are disparately reported to be influencedby body adiposity. This study tests the hypothesis that body adiposity exerts a sys-tematic influence on these muscle characteristics and evaluates the possible func-tional implications for movements. Lower limb SM volume (VSM) and attenuation(ATTSM), an inverse measure of lipid infiltration in muscle, were determined withcomputed tomography in 21 men (BMI = 21–36 kg m�2; age = 31–71 years.)and 18 women (BMI = 19–35 kg m�2; age = 32–76 years.). After adjusting forage, a multivariate regression analysis revealed that body adiposity positively corre-lated (P<0�05–0�001) with absolute VSM and cross-sectional area (CSA) in bothgenders, while VSM per unit body mass (VSM/BM) decreased with adiposity(P<0�001) in women and was constant in men. ATTSM was higher in men(P<0�05) and decreased (P<0�05) with adiposity in both genders. The product ofATTSM by average muscle CSA (predictor of maximal strength) and by VSM/BM(predictor of maximal dynamic performance) was lower in women (P<0�001) andwas reduced by age in both genders (P<0�05–0�01), while obesity had a negativeeffect (P<0�001) only on the predictor of performance. In conclusion, body adipos-ity significantly increases SM size and reduces ATTSM. Structural indicators account-ing for both quantitative and qualitative characteristics of SM may be usefulpredictors of the effects of obesity on motor function at different ages. With risingbody adiposity and advancing age, women appear mostly affected by the decline ofSM features relevant for motor performance.

Introduction

Specific motor functional capabilities are intrinsically related to

the dimensions of involved skeletal muscle (SM) (Maughan

et al., 1983; Fukunaga et al., 2001). Several common conditions

like body adiposity and ageing, beside inactivity, bed resting/

disuse and chronic illness influence structural properties of SM

with effects on the inherent capability of strength and power

generation due to a relative or absolute variation in muscle vol-

ume (Doherty, 2003; Lafortuna et al., 2005; Evans 2010).

Due to the recent surge of obesity epidemics with its asso-

ciated complications as well as the rising prevalence of obesity

in older adults (Flegal et al., 2002), the negative effects of adi-

posity excess on SM characteristics and performance in the

ages of life have gained a relevant clinical impact. In fact, an

important role is played by the restriction of the individual’s

work capacity in the accomplishment of basic daily activities

concurring to a good quality of life, as well as in the decline

of the functional status and overall increased risk of disability

(Janssen et al., 2002; Walter et al., 2009).

Under these perspectives, the understanding of the effects

of body adiposity on muscle size and composition during life

may have a relevant clinical importance. While the effects of

ageing processes per se on muscle mass and functions are well

established (see Doherty, 2003; for a review), the effects of

increased adiposity on muscle characteristics are still unde-

fined, estimation of SM in obese or overweight individuals

being mostly based on indirect evaluation of fat-free or lean

soft tissue mass, in spite of the considerable functional limita-

tions associated with body mass excess. In this condition, the

disproportionately augmented mass of fat tissue put muscles

at disadvantage during the execution of everyday life activities

as well as during specific exercise movements. In fact, body

mass excess imposes a burden limiting most motor capabili-

ties with a particularly disabling effect in women, who are

inherently endowed with a reduced amount of SM (Evers

Clin Physiol Funct Imaging (2014) 34, pp47–55 doi: 10.1111/cpf.12062

47© 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd 34, 1, 47–55

Larsson & Mattsson, 2001; Lafortuna, 2013). In spite of this,

several studies have evidenced a preservation or even an

increase in muscle strength in obese individuals during move-

ments of different body segments and under different condi-

tions (Hulens et al., 2001; Lafortuna et al., 2005), which was

no longer apparent when fat-free mass was accounted for,

suggesting that also the mass of involved muscles was aug-

mented in the condition of overweight/obesity.

Indeed, SM can be characterized by quantitative (size) and

qualitative (composition) structural attributes which concur in

determining functional performance and possibly impairment.

Abundant evidence supports a robust association between

muscle size and strength production on a general context

(Maughan et al., 1983; Fukunaga et al., 2001). On the other

side, disparate investigations have pointed out that also

changes in skeletal muscle composition due to a degree of fat

infiltration, such as observed in obesity, are associated with

reductions in muscle performance (Goodpaster et al., 2001;

Visser et al., 2005; Hilton et al., 2008). In spite of the apparent

effects of obesity on muscle size and composition, studies

exploring the variation in muscle dimension and fat infiltra-

tion are mainly focused on the contrast between groups of

persons in a specific condition and investigations on the sys-

tematic effect of the degree of body adiposity on trends of SM

characteristics are hardly available.

Methods based on different mathematical modelling of

body composition and using different principles of measure-

ments have been devised to achieve an indirect estimate of

total or regional SM mass (Janssen et al., 2000; Kim et al.,

2002). On the contrary, imaging techniques, such as com-

puted tomography (CT) and magnetic resonance imaging, can

provide a direct measurement of muscle tissue (Mitsiopoulos

et al., 1998; Ross et al., 2000). A major advantage of imaging

techniques is the tomographic visualization of body tissues,

which enables the volume reconstruction of total and regional

SM mass and avoids the approximation entailed in the use of

mathematical models and predictive equations. Moreover, SM

quality, related to adipose infiltration within the muscle, can

be studied with CT using voxel information about tissue atten-

uation (Goodpaster et al., 2000a).

Therefore, to test the hypothesis that body adiposity exerts

a direct influence on muscular characteristics and to evaluate

whether these changes may have functional implications for

movements, we determined volume and attenuation of the

lower limb SM from total CT images in a sample of individu-

als of both genders within a wide span of adiposity and age.

Subjects and methods

Subjects

Total body CT scans obtained in 39 subjects [21 males (mean

age � SD: 50�5 � 13�0 year, range: 31–71 year); 18 females

(mean age: 55�0 � 12�1 year, range: 32–76 year, P: not

significant)] were retrospectively analysed for lower limb

imaging. All subjects were undergoing a follow-up protocol

for melanoma diagnosed >24 months prior to the CT study

presently considered, and all were negative for a recurrence of

regional or distance disease thereafter, as assessed with repeated

routine total body clinical imaging (CT-Positron Emission

Tomography scans). Informed consent had been obtained from

all patients prior to the examinations in accordance with the

institutional ethics guidelines for clinical testing, and the pres-

ent analysis was anonymously conducted. For all patients, body

mass (males: mean, 80�4 � 12�1 kg, range, 60–120 kg;

females: mean, 64�5 � 12�4 kg, range, 49–90 kg, P<0�001)and height (males: mean, 1�75 � 0�06 m, range, 1�62–1�86 m; females: mean, 1�59 � 0�05 m, range, 1�50–1�67 m,

P<0�001) were obtained at the moment of examination and

body mass index (BMI) subsequently calculated (males: mean,

26�2 � 3�5 kg m�2, range, 21�4–35�9 kg m�2; females:

mean, 25�7 � 4�7 kg m�2, range, 19�0–34�7 kg m�2, p: not

significant). Waist circumference (WC) was determined from

the CT slice at mid-distance between iliac crest and rib cage,

according to the WHO criteria (World Health Organization,

1987). As an indicator of body adiposity, WC was expressed as

a ratio (WCr) with the values considered by the International

Diabetes Federation (Alberti et al., 2006) as the cut-off for cen-

tral obesity in Europids (i.e. 94 cm for males and 80 cm for

females). Average values of WCr were 1�02 � 0�12 (range

0�82–1�30) in men, and 1�10 � 0�17 (range 0�84–1�37) in

women, P: not significant. In both genders, a significant corre-

lation was found through linear regression between BMI and

WCr (men: BMI = 26�6 WCr–1�03, R2 = 0�811, P<0�001;women: BMI = 26�4 WCr–3�44, R2 = 0�877, P < 0�001).

Imaging technique

In all participant subjects, CT images were acquired by a Phi-

lips Gemini GXL tomograph (Philips Healthcare, Best, the

Netherlands) and consisted in a series of contiguous trans

axial slices, imaged as 512 9 512 voxel matrices with 5-mm

slice thickness and 1�17-mm pixel size.

A body segment comprised between the most cranial bor-

der of iliac crest and the apex of lateral malleolus was consid-

ered for image analysis in all subjects, and included buttock,

thigh and calf. The true anatomical length of the entire seg-

ment (LS) was calculated by accounting for knee and hip

angles possibly detected on CT images of the study, due to

occasional slight flexion spontaneously assumed by patients

during the examination. Slices were automatically processed

by a segmentation algorithm based on fuzzy c-mean approach

(Goldszal & Pham, 2000), using the public domain software

package (McAuliffe et al., 2001) Medical Image Processing,

Analysis and Visualization – MIPAV (Center for Information

Technology, National Institutes of health, available at http://

mipav.cit.nih.gov [last access 14 June 2013]).

After segmentation, voxels belonging to SM, adipose tissue

and bone were labelled with a component-specific numerical

values and could thus be discriminated. From the segmented

© 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd 34, 1, 47–55

Adiposity and human leg muscle features, C. L. Lafortuna et al.48

images, volumes of the different tissues were automatically

calculated as the sum of the voxels belonging to the specific

component multiplied by the voxel size. Volume rendering of

segmented images was achieved by means of a dedicated

commercial software (Amira v.4; Mercury Computer Systems,

Chelmsford, MA, USA) to visualize the three-dimensional

aspect of the lower limb tissue components. The volume of

SM (VSM) included all muscles with at least one insertion on

bone segments belonging to the lower limb, with exclusion

of ileus–psoas muscle. VSM was also expressed per unit limb

length (VSM/Ls), representing the ideal average muscle cross

section throughout lower limbs, and per unit body mass

(VSM/BM), representing the amount of muscle theoretically

available to support each unit of body load. Adipose tissue

volume was established by analysing slices representing the

true appendicular segment of lower limb, that is, ranging

from malleoli to a horizontal plane tangential to ischiatic

tuberosity, and included both subcutaneous and intermuscular

fat. Bone tissue comprised femur, patella, tibia and fibula. An

example of mid-thigh CT imaging, tissue segmentation and

whole limb tissue rendering representative of calculated

volumes is available in Fig. 1, for a typical male subject.

From the slices at mid-thigh, the mean CT attenuation coef-

ficient value for SM (ATTSM), which corresponds to the reci-

procal of lipid infiltration practically denoting the amount of

contractile elements within the muscle, was determined by

averaging the Hounsfield units intensity in voxels belonging

to the segmented muscle area.

To take into account the interaction between quantity and

quality of SM, the product VSM/Ls 9 ATTSM [related to mus-

cle section area, and expected to predict the strength capability

of the muscle (Maughan et al., 1983)] and VSM/BM 9 ATT-

SM [related to muscles volume relative to body mass, and

expected to predict the actual power performance (Lafortuna

et al., 2002)] were considered in the analysis.

Statistical methods

All values are given as means � SD. Significance of differences

between males and females was assessed with a Student’s t-test

for unpaired data. Regression line equations were calculated

with the least-square method and the differences between

regression lines were tested using conventional regression

equation comparison methods (Zar, 1984). The independent

effect of age and adiposity on muscle volume, cross-sectional

area and composition was evaluated by bivariate regression

analysis performed in men and women, separately. Multivari-

ate analysis of variance was performed to assess the indepen-

dent effect of gender, degree of adiposity and age on variables

combining size and composition of SM, in the whole sample.

P values <0�05 were considered statistically significant.

Results

The average values of VSM, mid-thigh muscle cross-sectional

area (CSASM) and ATTSM in lower limbs are presented in

Table 1, along with the values of adipose tissue and bone vol-

ume, while lower limb regional distribution of average cross-

section area of SM, adipose tissue and bone in the subjects

taking part in the study is shown in Fig. 2, for males and

females. As expected, the size of limb segments was smaller in

women, due to a significantly lower volume of SM and bone

and in spite of a significantly larger adipose tissue volume.

Therefore, the total volume of lower limbs was significantly

smaller in women than in men (21�6 L � 4�6 versus

25�0 L � 4�9, P<0�05). Similar gender differences in the tis-

sues of lower limbs were detected also when expressing the

values per unit body mass (P<0�001 for all tissues) and per

unit limb length (P<0�001 for all tissues). As shown in

Table 1, also average ATTSM was significantly lower in

women.

(a) (c)

(b)

Figure 1 Mid-thigh CT imaging (A), tissuesegmentation (B; light grey: skeletal muscle;dark grey: adipose tissue; white: bone; black:background) and whole limb tissue rendering(C) representative of calculated volumes in atypical male subject (age: 40 y; body massindex: 24�1 kg/m2).


Adiposity and human leg muscle features, C. L. Lafortuna et al. 49

The independent effect of body adiposity, as represented by

WCr, and age on lower limb SM characteristics was assessed

by means of a multiple linear regression analysis and the

resulting coefficients are presented in Table 2. In both gen-

ders, the analysis revealed that body adiposity and age had an

opposite independent effect on SM dimensional variables

(VSM, VSM/Ls and CSASM), while only body adiposity had a

negative effect on SM composition (i.e. on ATTSM), especially

in women. Moreover, in women, adiposity influenced nega-

tively also VSM/BM, representing the amount of lower limb

SM which functionally contributes to body mass support and

movement, whereas no effect was detected in males.

Therefore, in the individual subjects, high body adiposity

and advanced age had opposite effects on lower limb SM size,

with important differences among genders. In Fig. 3, the

value of VSM adjusted for age and expressed in both absolute

terms (panel A) or normalized by unit limb length (panel B)

is plotted as a function of body adiposity. Statistical compari-

son of regression lines obtained in men and women revealed

significantly different slopes (VSM: t = 4�09, P<0�001; VSM/

Ls: t = 4�40; P < 0�001), while similar trends between the

genders were observed for the decrease in both VSM and

VSM/Ls as a function of age (data not shown). Also VSM/BM

was similarly decreased by age in both genders, but it was

significantly reduced in women by body adiposity while unaf-

fected in men, as it can be appreciated from Fig. 4.

To explore the interaction between the changes in SM quan-

tity and quality and the impact for the overweight/obesity

0

100

200

300

400

500

600

700

–40 –20 0 20 40 60 80 100

CSA (

cm2)

Total Skeletal muscle Adipose tissue Bone

Men

Thigh

Calf

Buttocks

Knee Trochanter Ankle

0

100

200

300

400

500

600

700

–40 –20 0 20 40 60 80 100

CSA (

cm2)

Relative limb appendicular length (%)

Total Skeletal muscle Adipose tissue Bone

Women

Calf Thigh Buttocks

Trochanter Ankle Knee

Figure 2 Spatial distribution of cross-sectional area (CSA) of skeletal muscle, adiposetissue, bone and total tissue along the lowerlimb, expressed as relative appendicular length(from ischiatic tuberosity to malleoli) in men(upper panel) and women (lower panel).

Table 1 Average values (� SD) of skeletal muscle volume (VSM),mid-thigh muscle cross-sectional area (CSASM) and attenuation(ATTSM), together with volumes of adipose tissue (VAT) and bone(VBO) measured in lower limbs of the subjects taking part in the study.

Males (n = 21) Females (n = 18)

LS (cm) 97�5 � 4�6 87�1 � 3�3***VSM (L) 15�83 � 2�11 10�34 � 1�21***CSASM (cm2) 144�1 � 23�6 101�8 � 13�8***ATTSM (HU) 46�33 � 3�62 43�57 � 4�15*VAT (L) 6�84 � 3�09 9�48 � 3�94*VBO (L) 2�11 � 0�22 1�39 � 0�17***

LS denotes the length of lower limb segment considered for analysis(comprised between the most cranial border of iliac crest and theapex of lateral malleolus). CSASM was determined on right limbs. Adi-pose tissue volume was assessed in the appendicular segment of lowerlimb (comprised between a horizontal plane tangential to ischiatictuberosity and the apex of lateral malleolus); bone volume includesfemur, patella, tibia and fibula (see Methods for further details). Sig-nificance of differences between males and females is assessed with aStudent’s t-test for unpaired data.*P<0�05.***P<0�001.



condition, the product VSM/Ls 9 ATTSM (accounting for aver-

age muscle section area) and VSM/BM 9 ATTSM (accounting

for average muscles volume relative to body mass) were consid-

ered. These variables were analysed with a multivariate analysis

of variance after stratifying the whole sample for gender, for

BMI (normal weight, NW, with BMI ≤ 25 kg m�2; overweight

and obese, OW&OB, with BMI > 25 kg m�2) and for age

(younger and older, using the median age (i.e. 53 year.) as a

cut-off). The average values for men and women and for the

different strata of adiposity and age are shown in Table 3 along

with the results of the multivariate analysis. It appears that

VSM/BM 9 ATTSM (expected to predict the individual’s maxi-

mal power performance) is negatively affected by female gen-

der, overweight/obesity and advancing age, whereas VSM/

Ls 9 ATTSM (expected to predict strength maximal capability)

Table 2 Coefficients from multiple linear regression analysis model-ling the independent effect of age and body adiposity (as representedby WCr) on lower limb skeletal muscle characteristics in men andwomen taking part in the study: volume in absolute terms (VSM) orrelative to anatomical length (VSM/LS) and body mass (VSM/BM);mid-thigh cross-sectional area (CSASM) and attenuation (ATTSM).

Coefficient T P Multiple R2

Males (n = 21)VSM (L)Constant 4�960 2�361 0�030 0�759Body adiposity 15�622 7�062 <0�001Age �0�106 �5�178 <0�001

VSM/LS (cm2)Constant 58�60 2�336 0�031 0�658Body adiposity 146�9 5�561 <0�001Age �0�967 �3�959 <0�001

VSM/BM (cm3 kg�1)Constant 260�0 9�504 <0�001 0�305Body adiposity �41�48 �1�440 0�167Age �0�439 �1�650 0�116

CSASM (cm2)Constant 41�80 1�359 0�191 0�587Body adiposity 152�4 4�704 <0�001Age �1�067 �3�563 0�002

ATTSM (HU)Constant 63�803 11�00 <0�001 0�338Body adiposity �14�40 �2�287 0�035Age �0�054 �0�922 0�369

Females (n = 18)VSM (L)Constant 9�915 5�363 <0�001 0�393Body adiposity 3�067 2�051 0�058Age �0�054 �2�652 0�018

VSM/LS (cm2)Constant 110�0 6�034 <0�001 0�425Body adiposity 34�80 2�359 0�016Age �0�543 �2�711 0�025

VSM/BM (cm3 kg�1)Constant 312�5 16�00 <0�001 0�824Body adiposity �124�1 �8�041 <0�001Age �0�217 �1�036 0�316

CSASM (cm2)Constant 111�9 5�213 <0�001 0�376Body adiposity 24�35 1�402 0�181Age �0�672 �2�854 0�012

ATTSM (HU)Constant 60�153 9�625 <0�001 0�339Body adiposity �11�14 �2�529 0�023Age �0�081 �1�130 0�276

R = 0·683P < 0·001

R = 0·214P = 0·05

0

5

10

15

20

25

0·65 0·85 1·05 1·25 1·45

SM

volu

me

(l)

Men

Women

(a)

R = 0·602P < 0·001

R = 0·275P < 0·05

80

100

120

140

160

180

200

220

0·65 0·85 1·05 1·25 1·45

Body adiposity (WCr)

SM

volu

me

per

lim

b len

gth

(cm

2)

Men

Women

(b)

2

2

2

2

Figure 3 The relationship between lower limb skeletal muscle vol-ume and body adiposity. Muscle volume is adjusted for age andexpressed in absolute terms (panel A) or normalized by unit limblength (panel B). Regression lines through the data are also shown.Men (filled circles); women (open circles).

R = 0·039P = 0·392

R = 0·725P < 0·001

0·05

0·10

0·15

0·20

0·25

0·30

0·65 0·85 1·05 1·25 1·45

Body adiposity (WCr)

SM

volu

me

per

BM

(l kg

–1) Men

Women 2

2

Figure 4 The ratio between lower limb skeletal muscle and bodymass (BM) is plotted against body adiposity. Regression lines throughthe data are also shown. Men (filled circles); women (open circles).



is reduced by effect of female gender and advancing age but not

by the degree of body adiposity.

Discussion

The purpose of the study was to assess the effect of body adi-

posity on the characteristics of SM determined with CT imag-

ing and to evaluate the possible functional implications for

movement execution.

Well-grounded evidences indicate that CT imaging is a reli-

able reference method to estimate appendicular skeletal muscle

size and composition, and regional tissue distribution (Mitsio-

poulos et al., 1998; Goodpaster et al., 2000b). Using a correla-

tion approach in a sample of men and women within a

relatively wide range of adiposity (from normal weight to

obesity) and ages (from young adulthood to older age), this

study quantified the (age-independent) influence of body adi-

posity on SM characteristics, which consisted in a gender-spe-

cific positive linear effect on muscle size counterbalanced by a

significant decrease in muscle tissue density.

Although the loss of SM size with advancing age, also pres-

ently detected, is widely known (Doherty, 2003), the effect

of body adiposity on SM quantity and quality has been fairly

less well explored systematically.

Body adiposity and muscle size

The rise of BMI in the continuum from normal weight to

obesity was associated with a progressive increase in absolute

and relative lower limb volume and cross-sectional area of

SM, with a different trend in the two genders. Such a finding

can be viewed as the result of an adaptive muscle response to

increased body mass which acts as a chronic training load

during everyday motor activity. Accordingly, previous studies

detected a gender-related increase also in the amount of fat-

free mass (FFM) as a function of the degree of body adipos-

ity (Hulens et al., 2001; Lafortuna et al., 2005). Indeed, SM is

an adaptable tissue actively responding to mechanical loading,

besides to growth factors and nutrients, and is finely

regulated by a complex and not completely understood cellu-

lar signalling network ultimately controlling muscle protein

synthesis and sarcomere addition (Miyazaki & Esser, 2009).

Unfortunately, at present, no study has been performed to

detect the involvement of any regulatory process possibly

controlling the muscle response to the obesity-related

mechanical overload.

From present results, it can be established that overall leg

muscle volume increases on average by about 2�4 kg every

five BMI units in man and about 1�3 kg in women, when

variations due to age are accounted for.

We detected that women have in general less SM in lower

limbs and more adipose tissue than men, even when adjusted

for the different body size, as a reflection of a gender-related

difference in body composition. Moreover, men and women

seem also to undergo different changes in body composition

along with the increase in body adiposity. Due to the lower

enlargement of SM volume with raising adiposity, in women

of the present study, the ratio VSM/BM (which represents the

amount of the movement actuator in lower limbs available

per unit body mass) decreases considerably as a function of

BMI, with important functional implications, as discussed

below. Similar gender-related trends in the variation in FFM/

BM with the degree of body adiposity have also been reported

previously (Lafortuna et al., 2005).

This raises the hypothesis that different mechanisms may

intervene in men and women to regulate muscle size as a func-

tion of body adiposity. Because no information concerning

lifestyle of the subjects participant to the present study was

available, the role of a different attitude to leisure time physical

activity between genders could not be excluded (Mart�ınez-

Gonz�alez et al., 2001). Nevertheless, it has been observed that

even a prolonged heavy strength training stimulus induces a

significantly greater increase in muscle volume in males than in

females (Ivey et al., 2000). Beside a possible role of the higher

levels of masculine testosterone, several gender-related differ-

ences in the regulation of growth hormone, as differences in

body composition and fat distribution (Roelen et al., 1997),

and in leptin plasma concentration (Llopis et al., 1998), may

participate in determining such as a gender-dependent

response of muscle mass to the increase in body adiposity.

Among the anatomical parameters investigated in the study,

there are important determinants of muscle performance in

static conditions and during movements.

Several investigations report in obesity a maintained or aug-

mented capacity of maximal isometric and isotonic strength

production and higher leg absolute power output (Miyatake

et al., 2000; Hulens et al., 2001; Lafortuna et al., 2002). Inter-

estingly, in obese subjects, the stronger muscle groups, in

comparison with normal weight persons, were those mainly

involved in movements against the force of gravity (Lafortuna

Table 3 Mean values (� SD) of the product of muscle attenuation(ATTSM) by VSM/Ls and by VSM/MB for the different strata of gen-der, body mass index (BMI) and age, and results of multivariate anal-ysis of variance.

VSM/LS 3 ATTSM(cm2 3 HU)

VSM/BM 3 ATTSM(L kg�1 3 HU)

GenderMen 21 7412 � 988 Men 21 9�07 � 1�21Women 18 5150 � 556 Women 18 7�16 � 1�45

ObesityNW 18 6535 � 1430 NW 18 8�94 � 1�47OW&OB 21 6163 � 1376 OW&OB 21 7�55 � 1�50

AgeYounger 20 6863 � 1460 Younger 20 8�61 � 1�66Older 19 5847 � 1150 Older 19 7�74 � 1�51

Effects df F-ratio P Effects df F-ratio PGender 1 70�29 <0�001 Gender 1 26�66 <0�001Obesity 1 0�782 = 0�383 Obesity 1 20�93 <0�001Age 1 9�424 <0�01 Age 1 5�246 <0�05



et al., 2005), possibly reflecting the gravity-related nature of

the obesity overload. Nonetheless, as detectable with functional

tests (Lafortuna et al., 2002; Sartorio et al., 2004), obese sub-

jects have markedly reduced capabilities in tasks requiring the

development of explosive anaerobic power, such as climbing

stairs or executing vertical jumps with maximal effort. In fact,

the actual determinant of these performances is the power out-

put per unit body mass, which is notably decreased in persons

with excess of body mass (Lafortuna et al., 2002), due to the

disproportionate increase in fat mass relative to contractile ele-

ments which determine a low muscle to body mass ratio.

Body adiposity and muscle fat infiltration

Present results also reveal a significant reduction in ATTSM

detected through the Hounsfield Units scale of CT imaging for

the effect of body adiposity in both genders, on average

women presenting a lower value of ATTSM than men. Indeed,

attenuation characteristics of tissues in vivo, depending from

their density and electron per unit mass (Bushberg et al.,

1994), provide the basis for differentiating fat and muscle on

CT images and to assess the lipid content in muscle. Due to

the widely lower attenuation coefficient of fat, the interindi-

vidual variation in ATTSM has been shown to reflect the

degree of lipid infiltration (Goodpaster et al., 2000a). By

means of a quantitative evaluation of ATTSM, several investi-

gations detected a higher degree of such infiltration within

muscles in obesity and older age (Kelley et al., 1991; Ryan &

Nicklas, 1999) and found it to be associated with reduced

motor performances (Goodpaster et al., 2001; Visser et al.,

2005; Hilton et al., 2008), along with an increased metabolic

risk (Kelley et al., 1991; Goodpaster et al., 1997; Ryan & Nicklas,

1999). Hence, although muscle size is known to be the

major predictor of force production on a general contest

(Maughan et al., 1983; Fukunaga et al., 2001), qualitative

attributes related to muscle composition may be important in

determining the association between muscle mass and its

function.

Functional considerations

In practice, the structural gender-dependent changes associated

with body adiposity are expected to combine with the effects

induced by advancing age, and likely determine a complex sit-

uation for muscle functionality.

Thus, in older obese adults, the combination of increased

body adiposity reducing the relative size of lower limb SM

per unit body mass (and hence power) and advancing age

reducing the size of SM (and hence strength) produces a con-

dition with potentially very serious consequences on health

and disability (Jensen & Hsiao, 2010), especially for women

who are inherently provided with a smaller volume of muscle

with lower density and responding to adiposity overload with

a minor increase. In view of the rising number of obese older

individuals (Flegal et al., 2002), the detailed knowledge of the

concomitant effects induced on muscles by obesity and ageing

could be relevant for the appropriate identification, prevention

and treatment of this motor frailty.

To characterize the functional implications for movements

deriving from the different variations in muscular size and

composition, we devised an index integrating the trends in

leg muscle characteristics presently observed. Thus, ATTSM

(denoting the amount of contractile elements within the mus-

cle) was combined with VSM/Ls, representing the average

muscle section area in the lower limb and related to muscle

strength (VSM/Ls 9 ATTSM), and with VSM/BM, indicating

the average volume of lower limb muscle per unit body mass

and related to muscle explosive performance (VSM/BM

9 ATTSM). According with functional observations reporting

a decline of specific power output with a preserving of

strength capabilities in obesity (Hulens et al., 2001; Lafortuna

et al., 2002, 2005), the index denoting dynamic performance

results significantly reduced by female gender, overweight/

obesity condition and older age, while the strength index is

decreased by female gender and older age, but not by adipos-

ity excess. Thus, the concomitance of obesity and older age in

females appears to involve a particularly unfavourable condi-

tion for muscle structural characteristics expected to produce a

functional derangement of dynamic performance. As also

experimentally evidenced (Lafortuna et al., 2004), older

women with high degree of obesity are prone to suffer from

major dysfunctions in movements which may interfere with

everyday locomotor abilities and even lead towards thresholds

for impaired mobility. Nonetheless, although consistent with

functional observations, the physiological representativeness of

these structural indices should be carefully evaluated and

further investigation seems to be necessary.

In conclusion, this study revealed in this sample of subjects

that while advancing age had a negative effect on quantitative

attributes of lower limb SM, raising body adiposity had a

positive influence on these, but were also accompanied by

unfavourable qualitative changes represented by a reduction in

muscle density. Moreover, as the enlargement of SM size

under the effect of increasing body adiposity was notably less

prominent in females, who also have a lower muscle density,

overweight/obese women (especially in older age) experience

a conspicuous decrease in lower limb SM volume available for

sustaining body movements and appear to be more damaged

than men by the obesity-related imbalance between the

amount of contractile elements and body mass.

Although a previous diagnosis of melanoma common to all

participants to the study unlikely affected the characteristics of

SM presently investigated, our findings cannot be considered

as the outcome of a population-based investigation and gen-

eral conclusions should be drawn with some caution.

Nevertheless, implications deriving from these results may

have a potential clinical impact on the formulation of physical

activity protocols using exercise as an intervention tool for

treating body mass excess and contrasting motor disabilities of

overweight/obese individuals at different ages of life.



Acknowledgments

The authors gratefully thank Dr Luigi Gianolli, Department of

Nuclear Medicine, Scientific Institute San Raffaele, Milano,

Italy, for providing patient and CT data.

Funding

Partially financed by the project Platform for International Col-

laborative Knowledge on Food Improvement Based on Ecolog-

ical Resources (PICKFIBER), Grant No. 0120R1/21,

(subproject in the miniprogramme Innovation 4 Welfare),

funded by INTERREG IVC Programme.

Conflict of interest

The authors declare that there is no conflict of interest that

could be perceived as prejudicing the impartiality of the

reported information.

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Influence of body adiposity on structural characteristics of skeletal muscle in men and women

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