Strength Training Reduces Fat Accumulation and Improves Blood Lipid Profile Even in the Absence of Skeletal Muscle Hypertrophy in High-Fat Diet-Induced Obese Condition

Abstract

The aim was to investigate the effect of strength training on skeletal muscle morphology and metabolic adaptations in obese rats fed with unsaturated high-fat diet (HFD). The hypothesis was that strength training induces positive metabolic adaptations in obese rats despite impaired muscle hypertrophy. Male Wistar rats (n = 58) were randomized into two groups and fed a standard diet or a high-fat diet (HFD) containing 49.2% of fat. After induction and maintenance to obesity, the rats were divided into four groups: animals distributed in sedentary control (CS), control submitted to strength training protocol (CT), obese sedentary (ObS), and obese submitted to strength training protocol (ObT). The exercise protocol consisted of 10 weeks of training on a vertical ladder (three times a week) with a load attached to the animal’s tail. At the end of 10 weeks, strength training promoted positive changes in the body composition and metabolic parameters in obese animals. Specifically, ObT animals presented a reduction of 22.6% and 14.3% in body fat and adiposity index when compared to ObS, respectively. Furthermore, these rats had lower levels of triglycerides (ObT = 23.1 ± 9.5 vs. ObS = 30.4 ± 6.9 mg/dL) and leptin (ObT = 13.2 ± 7.2 vs. ObS = 20.5 ± 4.3 ng/mL). Training (ObT and CT) induced a greater strength gain when compared with the respective control groups. In addition, the weight of the flexor hallucis longus (FHL) muscle was higher in the ObT group than in the CT group, representing an increase of 26.1%. However, training did not promote hypertrophy as observed by a similar cross-sectional area of the FHL and plantar muscles. Based on these results, high-intensity strength training promoted an improvement of body composition and metabolic profile in obese rats that were fed a high-fat diet without skeletal muscle adaptations, becoming a relevant complementary strategy for the treatment of obesity.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1. Introduction

The prevalence of overweight and obesity has been increasing rapidly and globally, being considered a public health problem by the World Health Organization [1]. Obesity is a chronic multifactorial disease characterized by increased adipose tissue, leading to health hazards [1]. It is considered a relevant risk factor for the development of chronic noncommunicable diseases, such as cardiovascular diseases and type 2 diabetes mellitus, in addition to being associated with increased morbidity and mortality rates and reduction in life expectancy [2–5].

Physical exercise is indicated as an efficient strategy in the prevention and treatment of obesity, especially in obesity caused by high caloric intake and sedentary lifestyle [6, 7]. The benefits of regular exercise are related to decreased adipose mass, increased muscle mass, and protection against diseases that are associated with obesity [8, 9]. For gains of muscle strength and hypertrophy, strength training has been show to promote these adaptations in rodents and humans [10–14].

The American College of Sports Medicine recommends strength training as an auxiliary strategy in weight loss, aiming to improve the functional capacity by increasing the strength and muscle power and increasing the daily energy expenditure [8]. In addition, studies indicate that higher levels of muscular strength are associated with lower rates of risk factors associated with obesity and mortality [15–17]. Recent research has shown impairment in regeneration capacity of skeletal muscle in response to strength exercises in obese rats [18]. It is well known that muscle overload, as seen during strength training, leads to the activation of cell signaling pathways involved with muscle protein synthesis [19, 20]. In previous studies, inhibition of the Akt/mTOR pathway abolished muscle hypertrophy in a surgical overload model in mice [21]. Obesity induced by high-fat diet can lead to disruption of the Akt pathway and insulin resistance in peripheral tissues such as skeletal muscles [22]. However, the effects of obesity on protein synthesis in skeletal muscle and muscle hypertrophy in response to overload are still not well understood [23].

In this context, the objective of this current study was to evaluate the effect of strength training on skeletal muscle morphology and on metabolic adaptations in obese rats. The hypothesis was that strength training induces positive metabolic adaptations in obese rats despite impaired muscle hypertrophy.

2. Materials and Methods

2.1. Animals and Treatment

Fifty-eight male Wistar rats, with 30 days of age and initial weight of approximately 150 g, were used. The animals were kept in individual cages in controlled environment with temperature at 24 ± 2°C, humidity 55 ± 5%, and reversed light/dark cycle of 12 hours. All procedures used in the study were approved by the Ethics Committee on the Use of Animals (CEUA) of the Federal University of Espírito Santo (protocol number 16/2016).

2.2. Food Consumption

The animals received 40 g of feed daily, and after 24 hours, the remaining noningested amount was measured. Control animals received standard diet, and obese animals received an unsaturated high-fat diet. Water was supplied ad libitum.

2.3. Composition of Diets

The standard diet presented a caloric content of 2.92 kcal/g, 13.9% of calories from fat, 55.9% from carbohydrates, and 30.2% from proteins (Nuvilab CR1-Nuvital®, Colombo, Paraná, Brazil). In turn, the high-fat diet presented a caloric content of 3.65 kcal/g, 49.2% of calories from fat, 28.9% from carbohydrates, and 21.9% from proteins (RC Focus 2413, 2414, 2415, and 2416, Agroceres®, Rio Claro, São Paulo, Brazil). Animals fed with high-fat diet received a four-flavor cycle of the diet, in which the nutritional composition was the same except for the flavoring additives (cheese, bacon, chocolate, and vanilla). The high-fat diet was provided throughout the experimental protocol.

2.4. Experimental Design

After seven days of acclimatization, the animals were randomly distributed into two groups: (1) control (C, n = 29) and (2) obese (Ob, n = 29). The experimental protocol consisted of 26 weeks, divided into three moments, as shown in Figure 1. Moment 1 (M1) was the first two weeks of induction to obesity. When the mean body weight of experimental groups C and Ob presented statistical difference, the initial moment of obesity was characterized. After induction to obesity, the animals were kept under the same conditions for 14 consecutive weeks for maintenance of this condition, which we classified as moment 2 (M2). The training protocol, carried out for 10 weeks, determined moment 3 (M3).

[figure omitted; refer to PDF]

In relation to dietary intake, no difference was found between groups. However, a higher caloric intake was observed in Ob animals compared to C during the initial 16 weeks of the experimental protocol. Although there was no statistical difference in feed efficiency $p=0.07$, the treatment was efficient for body weight gain since weight gain in Ob animals was higher than in C animals (Table 1).

Table 1

Nutritional profile during the 16-week experimental protocol prior to strength training.

	Group
	C	Ob
Food consumption (g/day)	22.08 ± 1.8	21.74 ± 6.1
Caloric intake (kcal/day)	64.47 ± 5.3	79.35 ± 6.1${}^{\ast }$
Food efficiency (%)	4.54 ± 0.3	4.80 ± 0.4
Body weight gain (g)	331.65 ± 37.4	425.83 ± 35.1${}^{\ast }$

Data expressed as mean ± SD. C = control (n = 20) and Ob = obese (n = 16). ${}^{\ast }p<0.05$vs. C.

3.2. Effects of Training

Figure 3 shows the evolution of the body weight during the 10 weeks of strength training. Body weight of the ObS and ObT groups was higher compared to the CS and CT groups, respectively, throughout the training period. From the 5^th week of strength training onwards, ObT groups presented lower body weight when compared to the ObS. In relation to nutritional parameters during the training protocol (17 ^th to 26^th weeks), no difference in food consumption was found among groups. However, caloric intake (ObT: 77.5 ± 4.6 vs. CT: 62.9 ± 7.5; $p<0.05$) and feed efficiency (ObT: 0.70 ± 0.48 vs. CT: 0.19 ± 0.34; $p<0.05$) were higher in ObT when compared to CT. In addition, similar behavior was found in caloric intake (ObS: 82.1 ± 6.7 vs. CS: 64.2 ± 6.2; $p<0.05$) and feed efficiency (ObS: 1.6 ± 0.3 vs. CS: 0.69 ± 0.42, $p<0.05$) of the obese sedentary group. Moreover, besides similar caloric intake between the ObS and the ObT during training, there was significant difference in feed efficiency (ObS: 1.6 ± 0.3 vs. ObT: 0.70 ± 0.48, $p<0.05$), demonstrating the effectiveness of training on reduction of feed (data not shown).

[figure omitted; refer to PDF]

At the beginning of the training protocol, the groups showed no difference in relation to the absolute load. However, the ObT group had a lower relative load compared to the CT group; although the ObS group showed no difference in relation to the CS group, a $p\text{value\hspace{0.17em}of\hspace{0.17em}}0.055$ was found (Figure 4(a)). After the training period, the trained animals presented higher absolute load and greater force gain compared to their controls (ObT vs. ObS and CT vs. CS, respectively) (Figures 4(b) and 4(c)). Regarding the relative load, the trained groups presented greater load compared to their controls at the end of the experiment; the relative load was lower in the ObT group compared to the CT group (Figure 4(b)). Therefore, strength training was efficient for gaining muscle force; however, obesity seems to promote impairment in strength.

[figures omitted; refer to PDF]

At the beginning and at the end of the training period, the ObS and ObT groups presented higher body weight when compared to their CS and CT controls, respectively. At the end of 10 weeks of strength training, the FBW of the ObT group was lower than the ObS group. Bodyweight gain was higher in the ObT and ObS animals compared to the CT and CS animals, respectively. In addition, body weight gain was lower in the animals that underwent the training protocol (CT vs. CS; ObT vs. ObS). Body fat and adiposity index presented similar responses since the groups exposed to the HFD (ObT and ObS) presented higher values compared to their respective controls, CT and CS. Body fat and adiposity index were lower in the animals exposed to the HFD and submitted to the training protocol (ObT vs. ObS) (Table 2). In addition, the ObS and ObT groups presented higher leptin values in comparison to their respective controls, and the ObT group presented lower values in relation to the ObS. Although there was no difference in glucose levels under baseline condition, ObS and ObT rats presented higher levels of glucose at 60, 90, and 120 minutes in relation to their respective controls (Figure 5(a)). Nevertheless, the ObT was not able to reverse the glucose damage in ObS (Figure 5(a)). In addition, the same behavior was observed for AUC among the groups (Figure 5(b)). Total cholesterol in the ObS group was lower in comparison to the CS, but the triglyceride values were higher in the ObS group; ObT animals presented lower TG compared to the ObS group (Table 2). There was no difference in HDL levels among the groups.

Table 2

Adiposity, comorbidities, and hormonal parameters.

	Groups
	CS	ObS	CT	ObT
Initial body weight (g)	447.13 ± 34.12	555.13 ± 35.10a	465.37 ± 35.97	549.39 ± 39.50d
Final body weight (g)†	477.97 ± 36.76	654.31 ± 50.34a	471.85 ± 44.94	590.33 ± 46.65c,d
Body weight gain (g)	30.84 ± 22.80	99.19 ± 21.37a	6.48 ± 18.04b	40.94 ± 27.08c,d
Body fat (g)†	27.75 ± 5.01	68.2 ± 13.50a	27.30 ± 2.10	52.78 ± 12.66c,d
Adiposity index (%)	5.79 ± 0.86	10.35 ± 1.46a	5.83 ± 0.73	8.87 ± 1.71c,d
Leptin (ng/mL)${}^{\ast }$	5.57 ± 2.98	20.48 ± 4.35a	4.77 ± 2.36	13.24 ± 7.23c,d
Total cholesterol (mg/dL)	66.45 ± 9.10	55.86 ± 13.18a	64.05 ± 9.68	55.00 ± 8.39
HDL (mg/dL)	23.30 ± 3.05	22.86 ± 6.30	24.70 ± 3.16	24.06 ± 3.87
Triglycerides (mg/dL)	22.05 ± 5.99	30.36 ± 6.90a	19.60 ± 3.09	23.06 ± 9.50c

Data expressed as mean ± standard deviation. CS = sedentary control (n = 10); CT = control submitted to the strength training protocol (n = 10); ObS = sedentary obese (n = 7); ObT = obesity submitted to strength training protocol (n = 9); ^† =  data presented in median ± interquartile range. ${}^{\ast }$Number of animals submitted to leptin analysis: CS (n = 9); CT (n = 9); ObS (n = 7); ObT (n = 8). $p<0.05$: ^aObS vs. CT; ^bCT vs. CS; ^cObT vs. ObS; ^dObT vs. CT.

[figures omitted; refer to PDF]

Weight of FHL muscles of animals from the ObT group was higher compared to that from the CT group (Figure 6(a)) without alterations on the FHL/tibia (Figure 6(b)). However, no difference in plantaris weight and plantaris/tibia was observed among groups (Figures 6(d) and 6(e)). One specific alteration was visualized in tibia length since there were differences between ObT and CT groups (data not shown). Moreover, cross-sectional areas FHL and plantaris did not present statistical difference between the groups (Figures 6(c) and 6(f)).

[figures omitted; refer to PDF]

4. Discussion

The objective of this study was to evaluate the effects of strength training on skeletal muscle morphology and metabolic adaptations in the obesity condition. The main finding is that the strength training did not induce skeletal muscle hypertrophy, although positive metabolic adaptations were observed in these trained animals.

Experimental models that mimic the eating habits of the population have been used to elucidate the mechanisms of obesity and metabolic disorders [29]. Thus, to induce obesity, a hypercaloric and high-fat diet was used, containing 49.2% of the energy derived from fat. Our results show that treatment was effective in promoting obesity from the 2^nd week, corroborating with previous research [30, 31]. The difference in body weight of the C and Ob groups remained throughout the maintenance period to obesity, with body weight of Ob animals being 21% higher than C animals at the end of this period. The body weight gain was 28.39% in the Ob group compared to that in the C group after 16 weeks of experiment. Similarly, Sitnick et al. [32] found a 31% increase in body weight of animals that were fed a high-fat diet with 45% fat in relation to control animals after 14 weeks of experiment. At the end of the experiment, the body fat weight was 145.7% higher in the ObS animals compared to that in the CS group, and for the trained animals, body weight was found to be 93.33% higher in the ObT group than in the CT group. The adiposity index of the ObS animals was 78.7% higher compared to that of the CS and 52.1% higher for the ObT group compared to that of the CT.

The standard diet used in our study had a caloric content of 2.92 kcal/g, while the high-fat diet presented 3.65 kcal/g, representing a 25% increase in calories, which justifies the highest body weight gain in this group. Although food efficiency did not show any difference at the end of the maintenance period of obesity, the animals’ ability to convert the energy consumed into body weight was higher since the Ob group presented greater weight gain compared to C. Possibly, the efficiency feeding did not present any difference during the initial 16 weeks of the experimental protocol due to the fact that the rats were still growing during the first weeks [33].

For the biochemical parameters, there were changes under the influence of the HFD since the obesity model promoted glucose intolerance and hypertriglyceridemia in ObS rats, indicating the TG value 37.68% higher compared to that of the CS group. Thus, the obesity experimental models presented almost all the metabolic disorders, such as glucose intolerance and dyslipidemia; strength training, however, was only able to promote positive changes in TG, which was observed by a reduction in TG levels when compared to the ObS (24.04%).

The training protocol was efficient to promote positive adaptations in body weight and accumulation of fat in trained animals. As expected, body weight gain was higher in the ObT and ObS groups compared to the CT and CS groups, which may be justified by the higher caloric intake in the animals that were fed a high-fat diet (ObT and ObS). Although there was no difference in caloric intake, body weight gain was lower in the groups submitted to strength training than in the sedentary groups (ObT vs. ObS and CT vs. CS). Body fat and adiposity index also showed that the training was efficient to prevent the effects of the high-fat diet since the ObT group presented lower values for these parameters than the ObS group.

Another important finding is related to the effects of strength training on hormonal regulation. Leptin is an important hormone secreted by adipose tissue that has a role in the control of satiety, commonly found in high concentrations in obese individuals [34]. In the present study, the ObS and ObT groups presented higher values compared to their respective controls, CS and CT, at 267.68 and 177.56%. In relation to the obesity-induced groups, leptin levels were lower in the animals subjected to the strength training protocol. The ObS group presented a leptin concentration 54.68% greater than the ObT group, which can be justified by the body fat weight of 12.82% that was higher in the ObS animals. High blood leptin concentration and resistance to its action are noted occurrences in obesity [35]. Our findings suggest that obesity promoted leptin resistance to action, since even with high levels of leptin, food intake between groups was similar.

The training protocol used was the vertical ladder climbing model with the overload principle as it is the model that most resembles the physiological adaptations found in strength training in humans [12, 25, 36]. At the end of the training period, the groups were fed a high-fat diet presented with higher body weight in comparison to the C groups (ObT vs. CT and ObS vs. CS). From the 5^th week of training, the ObT group had lower body weight compared to the ObS group, showing that the training prevented the gain of body weight promoted by the high-fat diet. In addition, the weight of the soleus, tibial, and FHL muscles was higher in the ObT group, 19.5%, 15.8%, and 26.1%, respectively, compared to those of the CT group, indicating a possible combined effect of obesity and strength training for gain of muscle mass. However, no difference was observed in muscle hypertrophy between the ObT and CT groups in the AST of plantaris and FHL muscles (Figures 5(c) and 5(f)).

Other authors, using the stair climbing training model, also did not find changes in the skeletal muscle mass [36, 37]. Variations between the analyzed muscles, equipment structure, or training protocol may justify the divergence between the results [37]. As in training for humans, any change in the variables involved in the prescription of the stair climbing training protocol may affect the adaptive response of the animal and, consequently, the results of the study [38].

Although some studies have found skeletal muscle hypertrophy at 8 weeks of training, protocols spanning between 6 and 12 weeks may not be sufficient to produce significant adaptations in skeletal muscle [36]. The duration of the training protocol used lasted 10 weeks and may have an influence on the absence of hypertrophy in the analyzed muscles. In addition, the number of series performed, in which it was established from the results of the pilot study (mean 4.2, climbed per training session), may also have influenced the results. The training model used depends on the voluntary action of the animals, so the number of series performed may have underestimated the physical capacity of the animals; consequently, the muscular stimulation may not have been sufficient to generate hypertrophy.

The absence of muscle hypertrophy in response to the exercise protocol observed in all groups in our study makes it impossible to evaluate the effect of obesity on skeletal muscle hypertrophy induced by strength training. According to Garcia-Vicencio et al. [39] and Bollinger [40], excess body weight can act as a stimulus for chronic overload training promoting favorable muscle adaptations. However, Bollinger [40] points out that the increase in skeletal muscle mass seems to occur only in the muscles bearing the load. The mTOR protein is a key regulator for protein synthesis and skeletal muscle cell hypertrophy [21, 41], and increasing evidence shows dysregulation in the mTOR signaling pathway in diet-induced obesity models [32, 42, 43].

Although the training did not promote changes in muscle mass gain, a force gain was observed in the trained groups (CT vs. CS and ObT vs. CS). At the end of the protocol, the absolute strength of the CT group increased by 172.55% and of the ObT group by 149.06%. The increase in strength is not necessarily related to the increase in the area of muscle fibers, and the result found may be associated with the neural adaptations that occur with the overload stimulus [44]. Furthermore, at the beginning of the training period, the ObT group had lower relative strength compared to the CT group, and although the ObS group showed no difference in relation to the CS group, a $p\text{value\hspace{0.17em}of}0.055$ was found. At the end of this period, the trained groups presented greater relative strength compared to their controls (CT vs. CS and ObT vs. ObS). The relative strength of the ObT group was also lower compared to that of the CT group. In obesity, the increase in fat mass is greater than the increase in skeletal muscle mass, which means that skeletal muscle represents a smaller percentage of the total body mass. The relative decrease in muscle mass may partly explain the decrease in relative strength found in obesity [40]. However, recent studies suggest that the ability to produce skeletal muscle strength decreases in obesity [45, 46]. According to Gadducci et al. [47], the functional capacity of skeletal muscle can be assessed from its ability to produce force. Thus, obesity decreased the functional capacity of skeletal muscle in response to strength training in the present study.

The increase in skeletal muscle mass promotes an increase in the basal metabolic rate, contributing to the daily energy expenditure and metabolic health [8, 48]. However, as the muscles analyzed did not present hypertrophy, it is probable that the results found are justified by the higher energetic expenditure promoted by physical exercise and by the EPOC effect promoted by high-intensity training [49, 50].

5. Conclusions

The strength training protocol promotes strength gains, but it did not cause skeletal muscle hypertrophy in obesity induced by unsaturated high-fat diet. However, strength training induced positive alterations on adiposity and comorbidities such as reduction in body weight, body fat content, adiposity index, and plasma triglycerides, as well as leptin levels independent of skeletal muscle hypertrophy. These results suggest that high-intensity strength training may be a relevant complementary strategy in combination with nutritional and pharmacological interventions for the treatment of obesity.

Acknowledgments

We are grateful to Priscilla Spadeto Altoé for her assistance. This work was supported by the Fundação de Amparo à Pesquisa e Inovação do Espírito Santo—FAPES (grant numbers: 74434489/16 and 67655602/15)—and partially financed by the Coordination for Improvement of Higher Education Personnel—Brazil (CAPES)—Finance Code 001.67655602/15.

References

[1] World Health Organization, Obesity and Overweight, 2018. http://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight

[2] K. R. Fontaine, D. T. Redden, C. Wang, A. O. Westfall, D. B. Allison, "Years of life lost due to obesity," JAMA, vol. 289 no. 2, pp. 187-193, DOI: 10.1001/jama.289.2.187, 2003.

[3] N. Ouchi, J. L. Parker, J. J. Lugus, K. Walsh, "Adipokines in inflammation and metabolic disease," Nature Reviews Immunology, vol. 11 no. 2, pp. 85-97, DOI: 10.1038/nri2921, 2011.

[4] P. Poirier, T. D. Giles, G. A. Bray, "Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American heart association scientific statement on obesity and heart disease from the obesity committee of the council on nutrition, physical activity, and metabolism," Circulation, vol. 113 no. 6, pp. 898-918, DOI: 10.1161/circulationaha.106.171016, 2006.

[5] P. W. F. Wilson, R. B. D’Agostino, L. Sullivan, H. Parise, W. B. Kannel, "Overweight and obesity as determinants of cardiovascular risk: the Framingham experience," Archives of Internal Medicine, vol. 162 no. 16, pp. 1867-1872, DOI: 10.1001/archinte.162.16.1867, 2002.

[6] O. Ciabattari, A. Dal Pai, V. Dal Pai, "Efeito da natação associado a diferentes dietas sobre o músculo tibial anterior do rato: estudo morfológico e histoquímico," Revista Brasileira de Medicina Do Esporte, vol. 11 no. 2, pp. 121-125, DOI: 10.1590/s1517-86922005000200005, 2005.

[7] F. L. Torres-Leal, M. D. Capitani, J. Tirapegui, "The effect of physical exercise and caloric restriction on the components of metabolic syndrome," Brazilian Journal of Pharmaceutical Sciences, vol. 45 no. 3, pp. 379-399, DOI: 10.1590/s1984-82502009000300003, 2009.

[8] J. M. Jakicic, K. Clark, E. Coleman, "American college of sports medicine position stand. Appropriate intervention strategies for weight loss and prevention of weight regain for adults," Medicine and Science in Sports and Exercise, vol. 33 no. 12, pp. 2145-2156, DOI: 10.1097/00005768-200112000-00026, 2001.

[9] K. M. Fock, J. Khoo, "Diet and exercise in management of obesity and overweight," Journal of Gastroenterology and Hepatology, vol. 28 no. Suppl 4, pp. 59-63, DOI: 10.1111/jgh.12407, 2013.

[10] K. Baar, K. Esser, "Phosphorylation of p70(S6k) correlates with increased skeletal muscle mass following resistance exercise," American Journal of Physiology-Cell Physiology, vol. 276 no. 1, pp. C120-C127, DOI: 10.1152/ajpcell.1999.276.1.c120, 1999.

[11] F. B. Favier, H. Benoit, D. Freyssenet, "Cellular and molecular events controlling skeletal muscle mass in response to altered use," Pflügers Archiv—European Journal of Physiology, vol. 456 no. 3, pp. 587-600, DOI: 10.1007/s00424-007-0423-z, 2008.

[12] J. Cholewa, L. Guimarães-Ferreira, T. da Silva Teixeira, "Basic models modeling resistance training: an update for basic scientists interested in study skeletal muscle hypertrophy," Journal of Cellular Physiology, vol. 229 no. 9, pp. 1148-1156, DOI: 10.1002/jcp.24542, 2014.

[13] B. J. Schoenfeld, J. Grgic, D. Ogborn, J. W. Krieger, "Strength and hypertrophy adaptations between low- vs. High-load resistance training: a systematic review and meta-analysis," Journal of Strength and Conditioning Research, vol. 31 no. 12, pp. 3508-3523, DOI: 10.1519/jsc.0000000000002200, 2017.

[14] J. Grgic, L. C. Mcllvenna, J. J. Fyfe, "Does aerobic training promote the same skeletal muscle hypertrophy as resistance training? A systematic review and meta-analysis," Sports Medicine, vol. 49 no. 2, pp. 233-254, DOI: 10.1007/s40279-018-1008-z, 2018.

[15] T. Rantanen, T. Harris, S. G. Leveille, "Muscle strength and body mass index as long-term predictors of mortality in initially healthy men," The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, vol. 55 no. 3, pp. M168-M173, DOI: 10.1093/gerona/55.3.m168, 2000.

[16] A. Guadalupe-Grau, J. A. Carnicero, A. Gómez-Cabello, "Association of regional muscle strength with mortality and hospitalisation in older people," Age and Ageing, vol. 44 no. 5, pp. 790-795, DOI: 10.1093/ageing/afv080, 2015.

[17] E. Stamatakis, I.-M. Lee, J. Bennie, "Does strength-promoting exercise confer unique health benefits? A pooled analysis of data on 11 population cohorts with all-cause, cancer, and cardiovascular mortality endpoints," American Journal of Epidemiology, vol. 187 no. 5, pp. 1102-1112, DOI: 10.1093/aje/kwx345, 2018.

[18] D. Akhmedov, R. Berdeaux, "The effects of obesity on skeletal muscle regeneration," Frontiers in Physiology, vol. 4,DOI: 10.3389/fphys.2013.00371, 2013.

[19] M. Francaux, L. Deldicque, "Exercise and the control of muscle mass in human," Pflügers Archiv—European Journal of Physiology, vol. 471 no. 3, pp. 397-411, DOI: 10.1007/s00424-018-2217-x, 2019.

[20] G. R. Marcotte, D. W. D. West, K. Baar, "The molecular basis for load-induced skeletal muscle hypertrophy," Calcified Tissue International, vol. 96 no. 3, pp. 196-210, DOI: 10.1007/s00223-014-9925-9, 2015.

[21] S. C. Bodine, T. N. Stitt, M. Gonzalez, "Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo," Nature Cell Biology, vol. 3 no. 11, pp. 1014-1019, DOI: 10.1038/ncb1101-1014, 2001.

[22] F. Tremblay, A. Marette, "Amino acid and insulin signaling via the mTOR/p70 S6 kinase pathway. A negative feedback mechanism leading to insulin resistance in skeletal muscle cells," The Journal of biological chemistry, vol. 276 no. 41, pp. 38052-60, DOI: 10.1074/jbc.M106703200, 2001.

[23] M. R. Papasani, K. Thornton, Z. Yinggian, "Does obesity reduce load-induced muscle hypertrophy?," The Journal of Physiology, vol. 588 no. 11, pp. 1819-1820, DOI: 10.1113/jphysiol.2010.189357, 2010.

[24] A. J. Ferron, B. B. Jacobsen, P. G. Sant’Ana, "Cardiac dysfunction induced by obesity is not related to β -adrenergic system impairment at the receptor-signalling pathway," PLoS One, vol. 10,DOI: 10.1371/journal.pone.0138605.eCollection2015, 2015.

[25] T. A. Hornberger, R. P. Farrar, "Physiological hypertrophy of the FHL muscle following 8 weeks of progressive resistance exercise in the rat," Canadian Journal of Applied Physiology, vol. 29 no. 1, pp. 16-31, DOI: 10.1139/h04-002, 2004.

[26] D. P. Relling, L. B. Esberg, C. X. Fang, "High-fat diet-induced juvenile obesity leads to cardiomyocyte dysfunction and upregulation of Foxo3a transcription factor independent of lipotoxicity and apoptosis," Journal of Hypertension, vol. 24 no. 3, pp. 549-561, DOI: 10.1097/01.hjh.0000203846.34314.94, 2006.

[27] B. J. Rolls, D. J. Shide, "The influence of dietary fat on food intake and body weight," Nutrition reviews, vol. 50 no. 10, pp. 283-90, DOI: 10.1111/j.1753-4887.1992.tb02466.x, 1992.

[28] B. A. Taylor, S. J. Phillips, "Detection of obesity QTLs on mouse chromosomes 1 and 7 by selective DNA pooling," Genomics, vol. 34 no. 3, pp. 389-398, DOI: 10.1006/geno.1996.0302, 1996.

[29] A. M. Matias, W. M. Estevam, P. M. Coelho, "Differential effects of high sugar, high lard or a combination of both on nutritional, hormonal and cardiovascular metabolic profiles of rodents," Nutrients, vol. 10,DOI: 10.3390/nu10081071, 2018.

[30] R. Buettner, J. Schölmerich, L. C. Bollheimer, "High-fat diets: modeling the metabolic disorders of human obesity in rodents ∗," Obesity, vol. 15 no. 4, pp. 798-808, DOI: 10.1038/oby.2007.608, 2007.

[31] C. M. Boustany-Kari, M. Gong, W. S. Akers, Z. Guo, L. A. Cassis, "Enhanced vascular contractility and diminished coronary artery flow in rats made hypertensive from diet-induced obesity," International Journal of Obesity, vol. 31 no. 11, pp. 1652-1659, DOI: 10.1038/sj.ijo.0803426, 2007.

[32] M. Sitnick, S. C. Bodine, J. C. Rutledge, "Chronic high fat feeding attenuates load-induced hypertrophy in mice," The Journal of Physiology, vol. 587 no. 23, pp. 5753-5765, DOI: 10.1113/jphysiol.2009.180174, 2009.

[33] A. F. Nascimento, M. M. Sugizaki, A. S. Leopoldo, "Misclassification probability as obese or lean in hypercaloric and normocaloric diet," Biological Research, vol. 41, pp. 253-259, DOI: 10.4067/s0716-97602008000300002, 2008.

[34] R. Yang, L. A. Barouch, "Leptin signaling and obesity," Circulation Research, vol. 101 no. 6, pp. 545-559, DOI: 10.1161/circresaha.107.156596, 2007.

[35] A. B. Crujeiras, M. C. Carreira, B. Cabia, S. Andrade, M. Amil, F. F. Casanueva, "Leptin resistance in obesity: an epigenetic landscape," Life Sciences, vol. 140, pp. 57-63, DOI: 10.1016/j.lfs.2015.05.003, 2015.

[36] N. D. Duncan, D. A. Williams, G. S. Lynch, "Adaptations in rat skeletal muscle following long-term resistance exercise training," European Journal of Applied Physiology, vol. 77 no. 4, pp. 372-378, DOI: 10.1007/s004210050347, 1998.

[37] K. Bennell, C. Page, K. Khan, "Effects of resistance training on bone parameters in young and mature rats," Clinical and Experimental Pharmacology and Physiology, vol. 27 no. 1-2, pp. 88-94, DOI: 10.1046/j.1440-1681.2000.03211.x, 2000.

[38] W. K. Neto, W. A. de Silva, A. P. Ciena, C. A. Anaruma, E. F. Gama, "Vertical climbing for rodent resistance training: a discussion about training parameters," International Journal of Sports Science, vol. 6, pp. 36-49, DOI: 10.5923/s.sports.201601.07, 2016.

[39] S. Garcia-Vicencio, E. Coudeyre, V. Kluka, "The bigger, the stronger? Insights from muscle architecture and nervous characteristics in obese adolescent girls," International Journal of Obesity, vol. 40 no. 2, pp. 245-251, DOI: 10.1038/ijo.2015.158, 2016.

[40] L. M. Bollinger, "Potential contributions of skeletal muscle contractile dysfunction to altered biomechanics in obesity," Gait & Posture, vol. 56, pp. 100-107, DOI: 10.1016/j.gaitpost.2017.05.003, 2017.

[41] T. Schmelzle, M. N. Hall, "TOR, a central controller of cell growth," Cell, vol. 103 no. 2, pp. 253-262, DOI: 10.1016/s0092-8674(00)00117-3, 2000.

[42] S. Paturi, A. K. Gutta, S. K. Kakarla, "Impaired overload-induced hypertrophy in obese Zucker rat slow-twitch skeletal muscle," Journal of Applied Physiology, vol. 108 no. 1,DOI: 10.1152/japplphysiol.00330.2009, 2010.

[43] Z. Hu, H. Wang, I. H. Lee, "PTEN inhibition improves muscle regeneration in mice fed a high-fat diet," Diabetes, vol. 59 no. 6, pp. 1312-1320, DOI: 10.2337/db09-1155, 2010.

[44] P. V. Komi, "Training of muscle strength and power: interaction of neuromotoric, hypertrophic, and mechanical factors," International Journal of Sports Medicine, vol. 7 no. Suppl 1, pp. 10-15, DOI: 10.1055/s-2008-1025796, 1986.

[45] S. J. Choi, D. C. Files, T. Zhang, "Intramyocellular lipid and impaired myofiber contraction in normal weight and obese older adults," The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, vol. 71 no. 4, pp. 557-564, DOI: 10.1093/gerona/glv169, 2016.

[46] H. Rahemi, N. Nigam, J. M. Wakeling, "The effect of intramuscular fat on skeletal muscle mechanics: implications for the elderly and obese," Journal of The Royal Society Interface, vol. 12 no. 109,DOI: 10.1098/rsif.2015.0365, 2015.

[47] A. Gadducci, R. de Cleva, G. Santarém, P. Silva, J. Greve, M. Santo, "Muscle strength and body composition in severe obesity," Clinics, vol. 72 no. 5, pp. 272-275, DOI: 10.6061/clinics/2017(05)03, 2017.

[48] J. R. Speakman, C. Selman, "Physical activity and resting metabolic rate," Proceedings of the Nutrition Society, vol. 62 no. 3, pp. 621-634, DOI: 10.1079/pns2003282, 2003.

[49] E. Børsheim, S. Knardahl, A. T. Høstmark, R. Bahr, "Adrenergic control of post-exercise metabolism," Acta Physiologica Scandinavica, vol. 162 no. 3, pp. 313-323, DOI: 10.1046/j.1365-201x.1998.0321e.x, 1998.

[50] E. E. Børsheim, R. Bahr, "Effect of exercise intensity, duration and mode on post-exercise oxygen consumption," Sports Medicine, vol. 33 no. 14, pp. 1037-1060, DOI: 10.2165/00007256-200333140-00002, 2003.