Effects of ovariectomy and resistance training onlipid content in skeletal muscle, liver, and heart;fat depots; and lipid profile

Richard Diego Leite, Jonato Prestes, Celene Fernandes Bernardes,Gilberto Eiji Shiguemoto, Guilherme Borges Pereira, Josiane Oliveira Duarte,Mateus Moraes Domingos, Vilmar Baldissera, andSergio Eduardo de Andrade Perez

Abstract: The aim of the present study was to investigate the effects of resistance training on skeletal muscle lipid con-tent, liver lipid content, heart lipid content, fat depots, and lipid profile in ovariectomized rats. Wistar adult female ratswere divided into 4 groups (n = 10 per group): sedentary (Sed-Intact), sedentary ovariectomized (Sed-Ovx), strengthtrained (ChronicEx-intact), and strength trained ovariectomized (ChronicEx-Ovx). A 12-week strength-training period wasused, during which the animals climbed a 1.1-m vertical ladder with weights attached to their tails. The sessions were per-formed once every 3 days, with 4–9 climbs and 8–12 dynamic movements per climb. Ovariectomy increased liver lipidcontent and fat depots, and heart and muscle lipid content. There was an increase in the atherogenic index and a negativechange in lipid profile because of the ovariectomy. Resistance training decreased lipid content in the liver, soleus, and ti-bialis anterior, decreased fat depots (mesenteric and retroperitoneal), and changed the lipid profile, independently of ovar-ian hormone status. These results indicate the potential benefits of resistance training as an alternative strategy to controlthe effects of ovariectomy on fat depot, lipid profile, and tissue lipid content.

Key words: resistance training, ovariectomy, tissues lipid content, fat depots, lipid profile.

Resume : Cette etude se propose d’analyser les effets de l’entraınement a la force sur le contenu lipidique du muscle sque-lettique, du foie et du cœur ainsi que sur les reserves de graisse et le profil lipidique de rats ovariectomises. Des ratesadultes Wistar sont reparties dans quatre groupes de dix individus : sedentaires (Sed-intact), sedentaires et ovariectomisees(Sed-Ovx), entraınees a la force (ChronicEx-intact), entraınees a la force et ovariectomisees (ChronicEx-Ovx). Le pro-gramme d’entraınement a la force d’une duree de 12 semaines consiste a monter, avec des poids attaches a la queue, surune echelle de 1,1 m placee a la verticale. A tous les 3 jours les rats effectuent une seance comprenant 4 a 9 montees etpresentant chacune de 8 a 12 mouvements dynamiques. L’ovariectomie augmente le contenu lipidique du foie, du cœur,du muscle et des reserves de graisse. L’ovariectomie augmente l’index atherogene et modifie negativement le profil lipi-dique. L’entraınement a la force diminue le contenu lipidique du foie, du soleaire, du jambier anterieur, des reserves degraisse (mesentere et retroperitoine) et du profil lipidique, et ce, independamment de l’activite hormonale des ovaires. Cesobservations revelent les effets benefiques potentiels de l’entraınement a la force afin de controler les effets de l’ovariec-tomie sur les reserves de graisse, le profil lipidique et le contenu lipidique des tissus.

Mots-cles : entraınement a la force, ovariectomie, contenu lipidique tissulaire, reserves de graisses, profil lipidique.

[Traduit par la Redaction]

IntroductionOvariectomy has been used as an experimental animal

model to simulate menopause, and both are associated withincreased risk of coronary heart disease, losses in muscle(sarcopenia) and bone (osteopenia), and changes in bodycomposition, lipid profile, and fat deposition (Shinoda et al.2002; Kemmler et al. 2004; Moran et al. 2007; Shiguemoto

et al. 2007; Paquette et al. 2007a; Corriveau et al. 2008;Pighon et al. 2009a).

According to Toth et al. (2000), vital organs and tissuemetabolism are affected by ovarian hormone status, resultingin changes of body fat levels. It has been clearly establishedthat a decrease in ovarian hormones, in particular estrogen,promotes fat deposition and accumulation, mainly in pools

Received 4 August 2009. Accepted 18 September 2009. Published on the NRC Research Press Web site at apnm.nrc.ca on 11 December2009.

R.D. Leite,1 J. Prestes, G.E. Shiguemoto, G.B. Pereira, J.O. Duarte, M.M. Domingos, V. Baldissera, and S.E. de Andrade Perez.Department of Physiological Sciences, Federal University of Sao Carlos, Sao Carlos–Sao Paulo, Brazil.C.F. Bernardes. Life Sciences Center, Pontifical Catholic University of Campinas, Campinas–Sao Paulo, Brazil.

1Corresponding author (e-mail: rixleite@gmail.com).

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Appl. Physiol. Nutr. Metab. 34: 1079–1086 (2009) doi:10.1139/H09-116 Published by NRC Research Press

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as skeletal muscle, adipose tissue, and the liver (Latour et al.2001; Paquette et al. 2007a).

There is evidence that ovariectomy and menopause are as-sociated with the development of a hepatic steatosis state(Votruba and Jensen 2007; Paquette et al. 2007a; Pighon etal. 2009b). Two recent studies reported that there is a pro-gressive accumulation of fat in the liver over a 13-week pe-riod in ovariectomized rats, with no marked increase inplasma fat-free acid (Paquette et al. 2007a; Barsalani et al.2008). This process may be related to reduced lipid oxida-tion and increased lipogenesis (Paquette et al. 2008, 2009;Pighon et al. 2009b), demonstrating that estrogen acts intra-hepatically as a protective factor avoiding liver lipid infiltra-tion (Barsalani et al. 2008).

Nevertheless, there is growing concern regarding fat accu-mulation in tissues and organs, because of the chronic dis-eases associated with this process (e.g., insulin resistance,obesity, and hepatic steatosis) (Barsalani et al. 2008; Pa-quette et al. 2009). Thus, an investigation of strategies toprevent or attenuate the deleterious effects associated withovarian hormone decrease is necessary. Hormonal replace-ment has been used to reduce the fat mass caused by ovar-iectomy (Shinoda et al. 2002). However, there are somerisks associated with this therapy in humans, such as the in-creased incidence of some types of cancer (Stefanick et al.2006; Olson et al. 2007; Zhang et al. 2007).

In addition, exercise has been used as a nonpharmacolog-ical intervention to control the effects of ovariectomy andmenopause (Kemmler et al. 2004; Corriveau et al. 2008).Shinoda et al. (2002) analyzed the effect of regular endur-ance-type exercise in ovariectomized rats and found a signif-icant decrease in fat mass after 8 weeks. Corriveau et al.(2008) have shown that the association of resistance trainingand diet in ovariectomized rats reduced intra-abdominal fatdepots and plasma-free fatty acid levels and prevented liverlipid accumulation. A recent study found that resistancetraining in ovariectomized rats can be an interesting strategyto maintain metabolic changes (fat accumulation and adi-pose tissue decreases) after a period of mass loss (Pighon etal. 2009a).

Among exercise interventions, resistance training has beenshown to be efficient in the attenuation of sarcopenia andbody composition changes. However, the role of resistancetraining in preventing fat deposition and accumulation in dif-ferent tissues and organs in ovariectomized rats remains un-clear. Therefore, it is important to design experiments toelucidate how resistance training influences fat deposition,accumulation, and lipid profile in ovariectomized rats.

In view of the above-mentioned concerns, our hypothesiswas that resistance training and (or) ovarian hormones couldalter fat depots in skeletal muscle, the heart, and the liver, aswell as change the lipid profile. Thus, the aim of the studywas to investigate the effect of resistance training on liver,heart, and muscle lipid content, fat depot, and lipid profilein intact and ovariectomized rats.

Materials and methods

AnimalsForty female 13-week-old Wistar rats (Rattus novergicus

var. albinus, Rodentia, Mammalia) from the breeding colony

of the Federal University of Sao Carlos (UFSCar) (Sao Carlos–Sao Paulo, Brazil), with an initial mass of 250 ± 30 g,were used. The rats were housed in collective cages (5 ratsper cage) at a constant temperature of 23 ± 2 8C, and hada 12 h light : 12 h dark cycle, with light from 0600 to1800 hours. The animals received commercial rodent chow(Labina-Purina, Descalvado, Sao Paulo, Brazil) and waterad libitum. Food intake was not monitored during the ex-perimental period.

The research was approved by the Federal University ofSao Carlos Committee of Experimental Animals (protocolno. 048/2007). All animal procedures were conducted in ac-cordance with the Guide for care and use of laboratory ani-mals (National Research Council 1998).

Experimental groupsThe rats were randomly distributed into 4 experimental

groups (10 animals per group): (i) sedentary intact (Sed-Intact), (ii) sedentary ovariectomized (Sed-Ovx), (iii) trained(ChronicEx-Intact), and (iv) trained ovariectomized (Chron-icEx-Ovx). The Sed-Intact and Sed-Ovx animals were keptin their cages for 3 months without any type of exercise.The Sed-Ovx animals had their ovaries removed. The trainedanimals (ChronicEx-Intact and ChronicEx-Ovx) performed12 weeks of resistance exercise. The training started at thesame time for each group and is described below.

OvariectomyOvariectomy was performed when the rats were 13 weeks

old, according to the technique described by Kalu (1991),with ethyl ether as anesthetic. All animals that underwentsurgery procedures had 1 week of recovery.

Resistance exercise trainingDuring the 12 weeks of resistance training, climbing ses-

sions were performed once every 3 days. Initially, the ratswere adapted to the resistance training protocol, which re-quired that the animals climb a vertical ladder (1.1 m �0.18 m, 2-cm grid, 808 incline) with weights secured to therats’ tails. The size of the ladder induced the animals to per-form 8–12 movements per climb. The load apparatus wassecured to the tail by wrapping the proximal portion of thetail with a self-adhesive foam strip. A Velcro strap waswrapped around the foam strip and fastened. With the loadapparatus secured to the tail, each rat was placed at the bot-tom of the ladder and familiarized with climbing. If neces-sary, a stimulus with a tweezers was applied to the animal’stail to initiate movement. At the top of the ladder, the ratsreached a housing chamber (20 cm � 20 cm � 20 cm),where they were allowed to rest for 120 s. This procedurewas repeated until the rats would voluntarily climb the lad-der 3 consecutive times, without stimulus.

Three days after this familiarization, the first training ses-sion took place. It consisted of 4–8 ladder climbs while car-rying progressively heavier loads. The initial climb consistedof carrying a load that was 75% of the animal’s body mass.After this, an additional 30-g weight was added until a loadwas reached with which the rat could not climb the entirelength of the ladder. Failure was determined when the ani-mal could not progress up the ladder after 3 successive stim-uli to the tail. The highest load successfully carried the

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entire length of the ladder was considered the rat’s maximalcarrying capacity for that training session.

The next training sessions consisted of 4 ladder climbswith 50%, 75%, 90%, and 100% of the rat’s previous maxi-mal carrying capacity, determined in the previous session.During subsequent ladder climbs, an additional 30-g loadwas added until a new maximal carrying capacity was deter-mined. The resistance training protocol was adapted fromHornberger and Farrar (2004), according to the needs of thepresent research.

Tissue collection and analytic methodsTissues and muscles were removed in the following order:

liver, heart, soleus, gastrocnemius, extensor digitorium lon-gus (EDL), and tibialis anterior (TA). All tissue sampleswere frozen in liquid nitrogen for further analysis. Total lip-ids levels were determined by the sulphophospho-vanillincolorimetric method, adapted for tissue (Frings et al. 1972).

Adipose tissue collectionThe adipose tissue collection was performed according to

the descriptions of Cinti (2005). Urogenital, mesenteric, andretroperitoneal fat depots were collected, weighed, andstored at –80 8C.

Analytic methods and atherogenic indexImmediately after the sacrifice, blood was collected, cen-

trifuged (3000 r�min–1 (1157g) for 10 min at 4 8C), andstored at –80 8C until analyses of total triglycerides (TGL),total cholesterol (TC), and high-density lipoprotein (HDL).TGL, TC, and HDL concentrations were determined withthe use of a commercially available kit (Laborlab, SaoPaulo, Brazil) with sensitivity of 0.7 mmol�L–1, 0.14 mmol�L–1,and 0.5 mmol�L–1, respectively. Very low-density lipopro-tein (VLDL) was calculated from TGL by Friedewald’sformula: VLDL = TGL/5 (Friedewald et al. 1972). SerumLDL was determined by Friedewald’s formula: LDL =TC – HDL – (TGL � 0.2). The atherogenic index (AI)was determined according to the descriptions of Kamganget al. (2005): AI = TC – HDL/TC.

Statistical analysisAll data were presented as means ± standard error of the

mean. The statistical analysis was done initially by the Kol-mogorov–Smirnov normality test and by the homocedasticitytest (Bartlett criterion). All variables analyzed in the studypresented normal distribution and homocedasticity, 2-wayanalysis of variance (ANOVA) test was used to compare thevariables resistance exercise with ovariectomy. Tukey’spost-hoc test was applied in the event of a significant (p <0.005) F ratio. The software package Statistica 6.1 (StatSoftInc., Tulsa, Okla.) was used, with an a level of 0.05.

Results

Tissue lipid contentThere was a statistically significant interaction between

groups for liver lipid content. The ChronicEx-Intact grouppresented significantly lower lipid content than the Sed-Intact (p = 0.001), Sed-Ovx (p = 0.001), and ChronicEx-Ovx (p = 0.001) groups. The Sed-Ovx group presented

higher lipid content than the Sed-Intact (p = 0.036) andChronicEx-Ovx (p = 0.001) groups (Fig. 1). Similar resultswere found for heart lipid content. The Sed-Ovx grouppresented higher lipid content than the Sed-Intact group(p = 0.017). The ChronicEx-Intact group exhibited lowerlipid content than the Sed-Intact (p = 0.001), Sed-Ovx(p = 0.001), and ChronicEx-Ovx (p = 0.001) groups, asshown in Fig. 2. There was no statistically significant dif-ference (p = 0.156) between the ChronicEx-Ovx andSed-Ovx groups.

Statistically significant interactions between the interven-tions and groups were found for all muscles. The ChronicEx-Intact group exhibited lower muscle lipid content in the

Fig. 1. Liver lipid content for experimental groups. Values are pre-sented as means ± standard error of the mean; p £ 0.05 (n = 10each group). a, Statistically significant difference compared withSed-Intact; b, compared with Sed-Ovx; c, compared with ChronicEx-Intact. Sed-Intact, sedentary; Sed-Ovx, sedentary ovariectomized;ChronicEx-Intact, strength trained; ChronicEx-Ovx, strength trainedovariectomized.

Fig. 2. Heart lipid content for experimental groups. Values are pre-sented as means ± standard error of the mean; p £ 0.05 (n = 10each group). a, Statistically significant difference compared withSed-Intact; b, compared with Sed-Ovx; c, compared with ChronicEx-Intact. Sed-Intact, sedentary; Sed-Ovx, sedentary ovariectomized;ChronicEx-Intact, strength trained; ChronicEx-Ovx, strength trainedovariectomized.

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soleus, gastrocnemius, EDL, and TA (Fig. 3) than all theexperimental groups (p £ 0.01). The Sed-Ovx group pre-sented higher lipid content in all muscles compared withthe Sed-Intact group. Additionally, there was a statisticallysignificant interaction between the interventions (resistanceexercise � ovarian status), indicating that muscle lipidcontent changed differently, depending on ovarian status,so that the ChronicEx-Intact group presented lower musclelipid content than the ChronicEx-Ovx group in the soleus(p = 0.001) and TA (p = 0.001) (Fig. 3).

Fat depot massThere was no statistically significant difference between

experimental groups in urogenital fat depot (Table 1). The

Sed-Ovx group presented higher mesenteric fat depot thanthe Sed-Intact (p = 0.001), ChronicEx-Intact (p = 0.001),and ChronicEx-Ovx (p = 0.001) groups. There was no dif-ference between the ChronicEx-Intact and ChronicEx-Ovxgroups (p = 0.270) in mesenteric fat depot (Table 1).

The Sed-Ovx group presented higher retroperitoneal fatdepot mass than the Sed-Intact (p = 0.039), ChronicEx-Intact (p = 0.001), and ChronicEx-Ovx (p = 0.045) groups(Table 1). The ChronicEx-Intact group exhibited lower ret-roperitoneal fat pad mass than the Sed-Intact (p = 0.040)and ChronicEx-Ovx (p = 0.045) groups. However, in thesum of the 3 fat depots (urogenital, mesenteric, and retro-peritoneal), no statistically significant difference was ob-served between experimental groups (Table 1).

Fig. 3. Soleus, tibialis anterior, extensor digitorium longus (EDL), and gastrocnemius muscle lipid content for experimental groups. Valuesare presented as means ± standard error of the mean; p £ 0.05 (n = 10 each group). a, Statistically significant difference compared with Sed-Intact; b, compared with Sed-Ovx; c, compared with ChronicEx–Intact. Sed-Intact, sedentary; Sed-Ovx, sedentary ovariectomized; Chroni-cEx-Intact, strength trained; ChronicEx-Ovx, strength trained ovariectomized.

Table 1. Relative mass of fat tissue (grams per 100 g of body mass).

Fat depot Sed-Intact Sed-Ovx ChronicEx-Intact ChronicEx-OvxURO 2.37±0.11 2.59±0.28 2.35±0.09 2.49±0.27MES 1.19±0.03 1.63±0.09* 1.17±0.03{ 1.17±0.04{

RET 1.21±0.03 1.64±0.08* 1.12±0.01*,{ 1.24±0.04{,{

Note: All values are presented as means ± standard error of the mean. URO, urogenital;MES, mesenteric; RET, retroperitoneal.

*Significant difference from Sed-Intact (p £ 0.05).{Significant difference from Sed-Ovx (p £ 0.05).{Significant difference from ChronicEx–Intact (p £ 0.05).

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Lipid profileThere was a statistically significant interaction between

the interventions (resistance training � ovarian status) inTGL levels. The Sed-Ovx group presented lower TGL levels(p = 0.002) than the Sed-Intact group. The ChronicEx-Intactgroup exhibited lower TGL levels than the Sed-Intact (p =0.001), Sed-Ovx (p = 0.001), and ChronicEx-Ovx (p =0.001) groups (Table 2).

There was a significant interaction between the interven-tions and groups for TC and HDL. The Sed-Ovx group ex-hibited higher serum cholesterol than Sed-Intact (p = 0.004),as shown in Table 2. Cholesterol levels were lower in theChronicEx-Intact group than in the ChronicEx-Ovx group(p = 0.024) (Table 2). HDL was higher in the Sed-Intactgroup than in the Sed-Ovx group (p = 0.001), and lower inthe ChronicEx-Ovx group than in the ChronicEx-Intactgroup (p = 0.001). The ChronicEx-Ovx group presentedhigher HDL levels than the Sed-Ovx group (p = 0.010)(Table 2).

There was a significant interaction between interventionsand groups, so that serum VLDL was higher in the Sed-Intactgroup than in the Sed-Ovx group (p = 0.003), and lower inthe ChronicEx-Intact group than in the Sed-Intact (p =0.001), Sed-Ovx (p = 0.001), and ChronicEx-Ovx (p =0.001) groups. Additionally, LDL was higher in the Sed-Ovx group than in the Sed-Intact group (p = 0.001), andlower in the ChronicEx-Intact group than in the Sed-Intact,Sed-Ovx, and ChronicEx-Ovx groups (p = 0.020, p =0.001, and p = 0.004, respectively) (Table 2). There was asignificant interaction between interventions and groups forAI. The Sed-Ovx group presented a higher AI than theSed-Intact, ChronicEx-Intact, and ChronicEx-Ovx groups(p = 0.002, p = 0.001, and p = 0.047, respectively). TheChronicEx-Intact group exhibited a lower AI than the Sed-Intact and ChronicEx-Ovx groups (p = 0.048 and p =0.002, respectively) (Table 2).

DiscussionThe purpose of the study was to analyze the influence of

resistance training and ovariectomy on lipid content in skel-etal muscle, the liver, and the heart; intra-abdominal fat de-pot; and lipid profile. Our initial hypothesis was confirmed,in that resistance training decreased lipid content in theliver, soleus, and TA muscle, and decreased mesenteric andretroperitoneal fat depot. Additionally, resistance training

promoted positive changes in fat tissue accumulation, lipidprofile, and AI.

In the present study, ovarian hormone status exerted astrong influence on fat accumulation, evidenced by the in-creased liver lipid content and fat depots in ovariectomizedrats. However, our resistance training protocol was able topartially reduce liver lipid content and fat depots, even inthe absence of ovarian hormones (Table 1 and Fig. 1). Sev-eral studies have shown the relationship between hepatic es-teatosis and increased liver and intra-abdominal fat, as aresult of ovariectomy and menopause. (Paquette et al.2007a; Barsalani et al. 2008; Corriveau et al. 2008; Pighonet al. 2009a). There is strong evidence that liver and intra-abdominal fat accumulation in ovariectomized rats is associ-ated with increased food intake (Latour et al. 2001; Shinodaet al. 2002; Paquette et al. 2008), imbalance between path-ways of uptake, synthesis and oxidation or hepatic secretionof lipids (Barsalani et al. 2008; Paquette et al. 2008, 2009),and decreased liver fatty acid oxidation (Paquette et al.2009).

Corriveau et al. (2008) and Pighon et al. (2009a) foundthat resistance training attenuates adipose tissue and fat ac-cumulation in the liver after a food restriction period inovariectomized rats. In this sense, there is growing evidencethat resistance training stimulates lipid oxidation in the liverbecause of the activation of the AMP-activated protein kin-ase (AMPK) pathway (Park et al. 2002; Lavoie and Gauthier2006; Corriveau et al. 2008) and downregulation of lipo-genic enzymes by hepatic genes expression (Griffiths et al.1993; Paquette et al. 2008).

A study of the expression of key transcriptional factors re-lated to hepatic lipid regulation, such as the peroxisome pro-liferator-activated receptor (PPAR)a, sterol regulatoryelement-binding protein-1c (SREBP-1c), and stearoyl-CoAdesaturase-1 (SCD-1) (Paquette et al. 2008), demonstrated adecrease in lipid oxidation systems associated with thedownregulation of PPARa mRNA expression, and an in-crease in the expression of lipogenesis transcriptional factors(SREBP-1c and SCD-1) in ovariectomized rats (Paquette etal. 2008). Moreover, exhaustive exercise decreases SCD-1 inmouse liver (Dobrzyn et al. 2004). It is tempting to specu-late that resistance training could induce AMPK activationwith a decrease in the expression of transcription factors re-lated to lipogenesis, improving liver fat oxidation and conse-quently reducing liver lipid content.

Table 2. Effects of resistance training on serum TGL, TC, HDL, VLDL, LDL, and AI.

Sed-Intact Sed-Ovx ChronicEx-Intact ChronicEx-OvxTGL (nmol�L–1) 1.48±0.05 1.23±0.14* 0.68±0.07*,{ 1.39±0.13{

TC (nmol�L–1) 2.17±0.07 2.74±0.15* 2.11±0.07{ 2.44±0.11*,{,{

HDL (nmol�L–1) 0.61±0.04 0.44±0.01* 1.06±0.08*,{ 0.77±0.04*,{,{

VLDL (nmol�L–1) 0.29±0.01 0.25±0.03* 0.13±0.01*,{ 0.27±0.02{

LDL (nmol�L–1) 1.26±0.09 2.00±0.15* 0.92±0.31*,{ 1.39±0.10{,{

AI 1.88±0.09 2.57±0.17* 1.61±0.08*,{ 2.13±0.11{,{

Note: Values are presented as means ± standard error of the mean. TGL, triglycerides; TC, total cholesterol;HDL, high-density lipoprotein; VLDL, very low-density lipoprotein; LDL, low-density lipoprotein; AI, athero-genic index.

*Significant difference from Sed-Intact (p £ 0.05).{Significant difference from Sed-Ovx (p £ 0.05).{Significant difference from ChronicEx–Intact (p £ 0.05).

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According to Pighon et al. (2009a), several muscle groupsparicipate in the resistance program used in rats. Interest-ingly, the present study demonstrated that resistance trainingwas effective in promoting decreases in muscle lipid content(Fig. 3). The decreases observed in the soleus and TAmuscles in the trained groups (ChronicEx-Intact and Chron-icEx-Ovx) suggest that the muscle lipid content can be af-fected by muscle activation during the climb and musclemetabolic oxidative characteristic. AMPK activation also de-creases muscle and adipose tissue lipid content by stimulat-ing fat oxidation during and after exercise (Ruderman et al.2003; Lavoie and Gauthier 2006). Another possible mecha-nism is the cathecolamines-induced metabolic changes,which are related to lipid oxidation from visceral adiposetissue, caused by increased b3-adrenoreceptor function anddecreased a2-adrenoreceptor function (Chapados et al.2008).

Corriveau et al. (2008) and Pighon et al. (2009a) observeda decrease in intra-abdominal fat depots in ovariectomizedrats submitted to resistance training. According to Pighon etal. (2009a), the decrease in liver fat accumulation is accom-panied by a similar alteration in the adipose tissue of ovar-iectomized rats. The present data confirm the literaturebecause we have shown that resistance training decreasesthe mass of mesenteric and retroperitoneal fat depots.

Another physiological consequence of ovariectomy andmenopause is the accumulation of visceral fat, a risk factorfor metabolic syndrome development, which is associatedwith several metabolic systemic abnormalities such as dysli-pidemia, insulin resistance, diabetes mellitus, and hyperten-sion (Toth et al. 2000; Votruba and Jensen 2007; Chapadoset al. 2008). Therefore, our study presents promising resultsregarding the effectiveness of resistance training in reducingfat depots in ovariectomized rats (Table 1).

Ovariectomy also modified the serum lipid profile by in-creasing TC and LDL levels, and by decreasing TGL,VLDL, and HDL levels (Table 2). Our results confirmedthe evidence that ovariectomy negatively affects the lipidprofile (Liu et al. 2004; Paquette et al. 2007a; Corriveau etal. 2008). This lipid profile alteration is strongly associatedwith an increased risk of cardiovascular disease (Medina etal. 2003) and atherogenic profile in postmenopausal women(Schneider et al. 2006). On the other hand, our resultsshowed that resistance training increases the HDL level anddecreases the TC and LDL levels, independently of theovarian status (Table 2). These results may be related tolower levels of liver fat depots and muscle lipid content, de-creasing the availability of nonsterified fatty acid and result-ing in a better lipid profile (Lavoie and Gauthier 2006).

The AI is a parameter used to determine the risk ofatherosclerosis development. This parameter is influencedby HDL and TC levels, reflecting the balance between therisk and the protective lipoprotein forces (Dobiasova 2004).Some studies have used this parameter to verify the AI inmen (Wakabayashi and Kobaba-Wakabayashi 2002) and an-imals (Kamgang et al. 2005). We have shown that ovariec-tomy increased the AI, and resistance training decreased it,indicating a potential cardiovascular protection.

In addition, ovarian status demonstrated a strong influenceon heart lipid content, supported by the increased fat deposi-tion in the hearts of ovariectomized rats. In fact, it has been

shown that estrogen prevents myocardial injuries and leftventricular hypertrophy (Paquette et al. 2007b). Resistancetraining failed to blunt the accumulation of fat in the heartinduced by ovariectomy. Thus, our results suggest that thecardioprotective effect of resistance training on heart lipidcontent depends on the presence of estrogen, because resist-ance training was able to decrease the heart lipid content inthe intact, but not in the ovariectomized, rats (Fig. 2).

The present study was not designed to study the effect offood intake on fat tissue accumulation in ovariectomized an-imals. Therefore, food intake was not monitored, which canbe considered a study limitation. Several studies have dem-onstrated that there is an increase in food intake and a massgain in ovariectomized rats (Shinoda et al. 2002; Paquette etal. 2007a, 2009; Barsalani et al. 2008). However, a recentstudy from our research group showed no statistically signif-icant difference in body mass between intact and ovariec-tomized rats (Prestes et al. 2009). These published data, inaddition to the present results, indicate that resistance train-ing promoted positive changes in the rats’ body composi-tion.

In another study by our group, submitted for publication,we found that ovariectomized sedentary rats exhibited a de-creased soleus and TA cross-sectional area as comparedwith a sedentary intact group. Additionally, there was a sig-nificant increase in the soleus and TA cross-sectional areaafter a 12-week stair-climbing training period in intact andovariectomized rats. Although food intake was not moni-tored, these above-mentioned results can confirm that resist-ance training is a protective tool against the deleteriouseffects of ovariectomy.

In summary, the present study clearly indicates the poten-tial benefits of resistance training as an important alternativestrategy to control the effects of menopause and ovariec-tomy on fat depot, lipid profile, and tissue lipid content.These findings suggest possible steps to prevent the deleteri-ous effects on metabolism associated with decreased ovarianhormones. We suggest future studies with postmenopausalwomen and food intake control to confirm these positive ef-fects of resistance training on systemic parameters and fattissue deposition.

AcknowledgementsThe authors thank Mr. Jose Carlos Lopes for laboratory

technical assistance. Financial support was provided by theConsellho Nacional de Desenvolvimento Cientıfico e Tecno-logico (CNPq) and by the Exercise Physiology Laboratoryof Federal University of Sao Carlos (Sao Carlos, Brazil).

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