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Phys Act Nutr > Volume 24(3); 2020 > Article
Hwang, Seo, Kim, and Lim: Effect of mild-intensity exercise training with capsiate intake on fat deposition and substrate utilization during exercise in diet-induced obese mice

Abstract

[Purpose]

While the anti-obesity effects of exercise and capsiate are well-observed individually, the effect of exercise with capsiate intake has not been systematically explored yet. Therefore, the purpose of this study is to investigate whether the anti-obesity effects of exercise training can be further enhanced by capsiate intake.

[Methods]

8-week-old male mice were divided into 3 groups (n = 8 per group): sedentary group (SED; nontrained), exercise-trained group (EXE) and exercisetrained group with 10 mg/kg of capsiate intake (EXE+CAP). All mice were offered high-fat diet and water ad libitum. The mild-intensity treadmill training was conducted 5 times a week for 8 weeks. After 8 weeks, metabolism during exercise and abdominal fat weight were measured.

[Results]

Body weight and the rate of total abdominal fat were significantly less in EXE+CAP than in SED but not between EXE and SED. The average of respiratory exchange rate during exercise was significantly much lower in EXE+SED (p = 0.003) compared to the difference between EXE and SED (p = 0.025). Likewise, the fat oxidation during exercise was significantly much higher in EXE+SED (p = 0.016) compared to the difference between EXE and SED (p = 0.045). Then, the carbohydrate oxidation during exercise was significantly much lower in EXE+SED (p = 0.003) compared to the difference between EXE and SED (p = 0.028).

[Conclusion]

In conclusion, the anti-obesity functions of exercise training can be further enhanced by capsiate intake by increasing fat oxidation during exercise. Therefore, we suggest that capsiate could be a candidate supplement which can additively ameliorate obesity when combined with exercise.

INTRODUCTION

Obesity causes endocrine imbalances which can lead to various cardiovascular diseases and type 2 diabetes [1]. This is because excess adipose tissue actively releases a large amount of cytokines and bioactive mediators such as leptin, adiponectin, and interleukin-6 [2]. Obesity increases the risk of mortality [3,4] and is a persistent global health problem [5]. Thus, considerable efforts to treat obesity and obesity-related problems have been exerted globally.
Capsiate, which was discovered in ‘CH-19 sweet pepper,’ is a capsaicin analogue [6] (Figure 1). While capsaicin has a strong, spicy taste and tends to cause stomachaches [7,8], capsiate is not pungent [9] but can increase energy expenditure to an equal extent as capsaicin [10,11]. In previous studies, acute administration of capsiate significantly increased oxygen uptake at rest [11,12], blood norepinephrine concentrations [12], and activity of the sympathetic nervous system [13]. Moreover, capsiate intake for 2 weeks significantly reduced body weight, body fat percentage [14], and abdominal fat [11,15] in humans and rodents. Thus, capsiate has been considered a possible supplement that can ameliorate obesity [16,17].
Exercise is one of the primary and most efficient methods to manage obesity [18]. Exercise is not only a calory-burning activity itself but it also increases fat-free mass [19] and energy expenditure level at rest [20], which leads to an energy imbalance toward weight loss. Moreover, a very important feature of exercise training is that it can enhance the fat oxidation capacity during exercise [21,22] so that fat is preferentially oxidized over carbohydrates as a fuel source even when an equal volume of exercise is performed at an equal absolute exercise intensity [23]. Therefore, many studies are being conducted on constructing a form of exercise training that can consume more fat [24,25].
While it is well-observed that both exercise and capsiate have antiobesity effects, the effect of exercise with capsiate intake has not been elucidated. There was only one study that investigated the combinatorial effects of exercise and capsiate, but there were some limitations as this previous study did not strictly control the total amount of capsiate intake and exercise training [26]. On the contrary, the weight-loss effects of exercise with capsaicin were well documented [27-29]. Additionally, many nutritional supplements such as caffeine and green tea extract have been shown to enhance fat oxidation and improve endurance performance [30], however, there has been no study that has investigated the effects of exercise training with capsiate on substrate utilization during exercise. Therefore, the purpose of this study is to investigate whether the anti-obesity effects of exercise training can be further enhanced by capsiate intake according to a change of substrate utilization during exercise in diet-induced obese mice.

METHODS

Animal care

This study used male 8-week-old ICR mice. Before the study began, they were adapted to the laboratory environments. All mice were housed in standard plastic cages (4 mice per cage) under controlled humidity (50 ~ 55 %), temperature (23 ℃ ± 1 ℃) and lighting (12:12-hr lightdark cycle; lights on at 08:00 am) conditions with highfat (60 % fat of total kcal) diet (HFD; Research Diets, Inc., New Brunswick, NJ, USA) and water available ad libitum. This study was approved by Konkuk University Institutional Animal Care and Use Committee.

Study design

Mice were randomly divided into three groups (n = 8 per group): sedentary group (SED; non-trained), exercise-trained group (EXE) and exercise-trained group with 10 mg/kg of capsiate intake (EXE+CAP). SED and EXE were also orally administered the equal solvent without capsiate for 8 weeks.
Exercise training intensity was set at mild condition (about 60 % VO2max) to prevent concealing of capsiate effect from the training. The training using treadmill was conducted by 5 times a week for 8 weeks. To avoid decreasing relative exercise intensity, absolute exercise intensity had been gradually increased (Table 1). The mice were orally administered capsiate 30 min before training.

Body weight, food intake and abdominal adipose tissue measurement.

Body weight (BW) and food intake were measured every day. At the end of the experiment, epididymal, perirenal and mesenteric fat were surgically obtained from the deeply anesthetized mice. Total abdominal fat was calculated from the sum of epididymal, perirenal and mesenteric fats. All tissues were weighed just after being dissected and subsequently stored at -80 ℃.

Metabolic analysis during exercise[31]

To investigate the effect of exercise training with capsiate intake on substrate utilization during exercise, metabolic analysis during exercise was conducted on the last weekend of the experiment for an hour at 13 m/min while fixed at 8 ° slope. The mice were orally administered capsiate 30 min before measurement. Mice were solely separated one by one in the metabolic treadmill chamber to measure energy metabolism during exercise. Respiratory gas (O2 uptake and CO2 production) was analyzed by a mass spectrometer (model RL-600, Alco System, Chiba, Japan) and switching system (model ANI6-A-S, Alco System) which allows the spectrometer to sample the gas from each chamber. Respiratory exchange rate (RER), fat oxidation (FO), carbohydrate oxidation (CO) and exergy expenditure (EE) were calculated from the measured respiratory gas.

Statistical analysis

All data were analyzed using IBM SPSS statistics 25 software. Significant differences in the values of average were determined using a one-way ANOVA, followed by Tukey’s HSD. Significant differences in the values over time were determined using a two-way repeated ANOVA. Values of p < 0.05 were considered statistically significant and all results are presented as mean ± standard deviation (S.D.).

RESULTS

Body weight, food intake (FI) and feed efficiency ratio (FER)

At the beginning of experiment, there was no difference in BW. After 8 weeks, however, there was significant difference in BW. The post-BW was significantly lower in EXE+CAP than in SED, but there was no difference in BW between EXE and SED. Interestingly, the total amount of FI was significantly higher in EXE+CAP than the others and there was also significant difference in FI between EXE and SED. Consequently, FER of EXE+CAP was significantly lower than that of SED but there was no difference in FER between SED and EXE (Table 2.).

The rate of adipose tissue

There was no significant difference in the rate of epididymal and perirenal fats. However, there was a clear trend that EXE+CAP showed the lowest rate of epididymal and perirenal fats. The rate of mesenteric fat was significantly less in EXE+CAP than SED but there was no difference in the rate of mesenteric fat between SED and EXE. Consequently, the rate of total abdominal fat was significantly less in EXE+CAP than SED but there was no difference between SED and EXE (Table 2.).

Metabolism during exercise

An important feature of exercise training which contributes to the control of body weight is that substrate utilization during exercise could be changed. After 8 weeks, a significant time, group and interaction effects were observed in RER, FO and CO over time (Figure 2A-C.), and there was only a significant time effect in EE over time (Figure 2D.). The average of RER for an hour was lower in EXE than in SED (p = 0.025) (Figure 3A.). However, it was significantly much lower in EXE+CAP than SED (p = 0.003) (Figure 3A.). Likewise, the total of FO for an hour was much higher in EXE+CAP (p = 0.016) compared to the difference between EXE and SED (p = 0.045) (Figure 3C.). Subsequently, the total of CO for an hour was significantly much lower in EXE+CAP (p = 0.003) compared to the difference between EXE and SED (p = 0.028) (Figure 3D.). Consequently, there was no difference in the total of EE for an hour among groups (Figure 3B.). These results indicate that FO capacity which was enhanced by exercise training could be further enhanced by capsiate intake.

DISCUSSION

The purpose of this study was to investigate whether weight-loss effect of exercise training can be further enhanced by capsiate intake. The results of this study showed that BW was additionally reduced in EXE+CAP compared with EXE despite the higher FI. Furthermore, while there was no difference in the rate of total abdominal fat between SED and EXE, the rate of total abdominal fat was less in EXE+CAP than SED. Thus, we demonstrated that exercise training with capsiate intake was able to additionally reduce BW and the rate of total abdominal fat. Considering the results of metabolism during exercise, this synergetic effect in EXE+CAP may result from FO capacity which was further enhanced by capsiate intake.
Capsiate intake activates sympathetic nervous system [32,33]. Subsequently, catecholamines are released from adrenal medulla which is stimulated by sympathetic nerve. Catecholamines promote fat utilization and thermogenesis [34,35]. In previous studies, epinephrine and norepinephrine levels in plasma were increased by acute treatment of capsiate in humans [12] and rodents [32]. In addition, the mRNA levels of CPT1 and FAT/CD36 (principal transporters of fatty acids) in liver and adipose tissue were increased more than 3-fold by 12 weeks of capsiate intake [36]. Likewise, total FO at rest was increased by 2 weeks of capsiate intake in rodents [15,37] and the average of RER for 30 min at rest was reduced by acute treatment of capsiate in humans [12]. Considering the previous reports, capsiate intake before exercise could play a role as a ‘warm up’ for the oxidation of fat during exercise.
As previously mentioned, FO rate during exercise could be higher depending on metabolic ability [23] or type of exercise [38] despite equal energy expenditure, which can result in a greater loss of body fat. In the previous studies, similarly, Sigal et al. [39] compared the effect of aerobic (FO predominant type) and resistance (CO predominant type) exercises for 6 months on various health indices. There were significant differences in body weight, waist circumference and fat mass between the control and the aerobic training groups but not between the control and the resistance training groups. Also from another study of aerobic and resistance exercise interventions for 12 weeks, body weight and subcutaneous adipose tissue in abdomen were more reduced by 40 % and 70 % respectively in the aerobic group than in the resistance group [40]. Considering the previous studies, likewise, it seems reasonable that greater reduction in the rate of total abdominal fat in EXE+CAP compared with EXE resulted from the additionally enhanced FO during exercise.
Although we demonstrate that the anti-obesity effects of exercise training can be further enhanced by capsiate intake, there may be two limitations in the current study. First, a non-trained group with capsiate intake was not included. The reason why we excluded this group is that our main interest was to explore whether the rate of FO which was increased by exercise training could be further enhanced by capsiate intake or not. Second, we did not analyze the genomics or proteomics related to energy metabolism. Thus, further studies are needed to be done on these perspectives.
In conclusion, the anti-obesity effects of exercise training can be further enhanced by capsiate intake according to the increase of FO during exercise. Therefore, we suggest that capsiate could be a candidate supplement which can additively ameliorate obesity when combined with exercise training.

Acknowledgments

This work was supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (NRF-2019S1A5B8099542).

Fig. 1.
The chemical structure of capsaicin (A) and capsiate (B).
pan-2020-0014f1.jpg
Fig. 2.
(A), (B), (C) and (D) The changes over time of RER, FO, CO and EE during exercise for an hour, respectively. Values represent the mean ± S.D. (n = 8).
pan-2020-0014f2.jpg
Fig. 3.
(A) The average of RER and (B), (C) and (D) the total of EE, FO and CO during exercise for an hour, respectively. Values represent the mean ± S.D. (n = 8). *p < 0.05; **p < 0.01.
pan-2020-0014f3.jpg
Table 1.
The protocol of mild-intensity exercise training.
Weekend 1st 2nd 3rd 4th 5th 6th 7th 8th
Duration (min) 20 30 40 50 60
Velocity (m/min) 13 14 15 16
Slope (°) 8
Table 2.
The results of body weight, body weight gain, food intake, feed efficiency ratio and the rate of adipose tissue.
SED EXE EXE+CAP
BW (g) Pre 34.91 ± 1.87 35.28 ± 1.84 34.69 ± 1.48
Post 47.79 ± 1.54a 46.95 ± 4.70ab 44.03 ± 1.22b
BWG (g/8 wk) 12.88 ± 2.36 11.68 ± 4.51 9.34 ± 1.15
FI (g/8 wk/mouse) 177.7 ± 3.00a 188.5 ± 11.1b 201.5 ± 3.96c
FER (BWG/FI*100) 7.26 ± 1.42a 6.21 ± 2.36ab 4.64 ± 0.61b
Adipose tissue (mg/bw g)
Epididymal 37.33 ± 4.74 33.50 ± 9.11 28.53 ± 8.70
Perirenal 15.34 ± 3.99 16.71 ± 6.53 11.11 ± 2.88
Mesenteric 27.40 ± 3.21a 25.09 ± 2.92ab 22.58 ± 3.65b
Total 80.07 ± 7.15a 75.30 ± 18.1ab 62.21 ± 14.6b

Note: Values represent the mean ± S.D. (n = 8). Different subscripts indicate a significant difference from each other. p < 0.05

REFERENCES

1. Foss ML, Keteyian SJ. Fox’s physiological basis for exercise and sport. NY: McGraw-Hill Company; 1998.

2. Scherer PE, Hill JA. Obesity, diabetes, and cardiovascular diseases. Circ Res 2016;118:1703-5.
crossref pmid pmc
3. Van Gaal LF, Mertens IL, DeBlock C. Mechanisms linking obesity with cardiovascular diease. Nature 2006;444:875-80.
crossref pmid pdf
4. Franks PW, Hanson RL, Knowler WC, Sievers ML, Ben-nett PH, Looker HC. Childhood obesity, other cardiovascular risk factors, and premature death. N Engl J Med 2010;362:485-93.
crossref pmid pmc
5. Xu H, Cupples LA, Stokes A, Liu CT. Association of obesity with mortality over 24 years of weight history: findings from the Framingham heart study. JAMA Netw Open 2018;1:e184587.
crossref pmid pmc pdf
6. Eanes L. Obesity: a persistent global health problem. Int Arch Nurs Heal Care 2015;1:1-3.
crossref
7. Yazawa S, Suetome N, Okamoto K, Namiki T. Content of capsaicinoids and capsaicinoid-like substances in fruit of pepper(capsicum annuum L.) hybrids made with “CH-19 Sweet” as a parent. J Japanese Soc Hortic Sci 1989;58:601-7.
crossref
8. Belza A, Jessen AB. Bioactive food stimulants of sympathetic activity: Effect on 24-h energy expenditure and fat oxidation. Eur J Clin Nutr 2005;59:733-41.
crossref pmid pdf
9. Lejeune MPGM, Kovacs EMR, Westerterp-Plantenga MS. Effect of capsaicin on substrate oxidation and weight maintenance after modest body-weight loss in human subjects. Br J Nutr 2003;90:651-9.
crossref
10. Iida T, Moriyama T, Kobata K, Morita A, Murayama N, Hashizume S, Fushiki T, Yazawa S, Watanabe T, Tominaga M. TRPV1 activation and induction of nociceptive response by a non-pungent capsaicin-like compound, capsiate. Neuropharmacology 2003;44:958-67.
crossref pmid
11. Kwon DY, Kim YS, Ryu SY, Cha MR, Yon GH, Yang HJ, Kim MJ, Kang S, Park S. Capsiate improves glucose metabolism by improving insulin sensitivity better than capsaicin in diabetic rats. J Nutr Biochem 2013;24:1078-85.
crossref pmid
12. OhnukI K, Haramizu S, Oki K, Watanabe T, Yazawa S, Fushiki T. Administration of capsiate promotes energy metabolism and suppresses body fat accumulation in mice. Biosci Biotechnol Biochem 2001;65:2735-40.
crossref pmid
13. Josse AR, Sherriffs SS, Holwerda AM, Andrews R, Staples AW, Phillips SM. Effects of capsinoid ingestion on energy expenditure and lipid oxidation at rest and during exercise. Nutr Metab 2010;7:1-10.
crossref
14. Ono K, Tsukamoto-Yasui M, Hara-Kimura Y, Inoue N, Nogusa Y, Okabe Y, Nagashima K, Kato F. Intragastric administration of capsiate, a transient receptor potential channel agonist, triggers thermogenic sympathetic responses. J Appl Physiol 2011;110:789-98.
crossref pmid
15. Kawabata F, Inoue N, Yazawa S, Kawada T, Inoue K, Fushiki T. Effects of CH-19 Sweet, a non-pungent cultivar of red pepper, in decreasing the body weight and suppressing body fat accumulation by sympathetic nerve activation in humans. Biosci Biotechnol Biochem 2006;70:2824-35.
crossref pmid
16. Haramizu S, Kawabata F, Masuda Y, Ohnuki K, Watanabe T, Yazawa S, Fushiki T. Capsinoids, non-pungent capsaicin analogs, reduce body fat accumulation without weight rebound unlike dietary restriction in mice. Biosci Biotechnol Biochem 2011;75:95-9.
crossref pmid
17. Ludy MJ, Moore GE, Mattes RD. The effects of capsaicin and capsiate on energy balance: Critical review and meta-analyses of studies in humans. Chem Senses 2012;37:103-21.
crossref pmid pdf
18. Zsiborás C, Mátics R, Hegyi P, Balaskó M, Pétervári E, Szabó I, Sarlós P, Mikó A, Tenk J, Rostás I, Pécsi D, Garami A, Rumbus Z, Huszár O, Solyámr M. Capsaicin and capsiate could be appropriate agents for treatment of obesity: a meta-analysis of human studies. Crit Rev Food Sci Nutr 2018;58:1419-27.
crossref pmid
19. Petridou A, Siopi A, Mougios V. Exercise in the management of obesity. Metab: Clin Exp 2019;92:163-9.
crossref
20. Solberg PA, Kvamme NH, Raastad T, Ommundsen Y, Tomten SE, Halvari H, Waaler N, Hallén J. Effects of different types of exercise on muscle mass, strength, function and well-being in elderly. Eur J Sport Sci 2013;13:112-25.
crossref
21. Henderson GC, Fattor JA, Horning MA, Faghihnia N, Johnson ML, Mau TL, Luke-Zeitoun M, Brooks GA. Lipolysis and fatty acid metabolism in men and women during the postexercise recovery period. J Physiol 2007;584:963-81.
crossref pmid pmc
22. Bagley L, Slevin M, Bradburn S, Liu D, Murgatroyd C, Morrissey G, Carroll M, Piasecki M, Gilmore WS, McPhee JS. Sex differences in the effects of 12 weeks sprint interval training on body fat mass and the rates of fatty acid oxidation and VO 2 max during exercise. BMJ Open Sport Exerc Med 2016;2:e000056.
crossref pmid pmc
23. Scharhag-Rosenberger F, Meyer T, Walitzek S, Kindermann W. Effects of one year aerobic endurance training on resting metabolic rate and exercise fat oxidation in previously untrained men and women. Int J Sports Med 2010;31:498-504.
crossref pmid pdf
24. Gaitán JM, Eichner NZM, Gilbertson NM, Heiston EM, Weltman A, Malin SK. Two weeks of interval training enhances fat oxidation during exercise in obese adults with prediabetes. J Sport Sci Med 2019;18:636-44.

25. Astorino TA, Schubert MM. Changes in fat oxidation in response to various regimes of high intensity interval training (HIIT). Eur J Appl Physiol 2018;118:51-63.
crossref pdf
26. Zhang H, Tong TK, Qiu W, Zhang X, Zhou S, Liu Y, He Y. Comparable effects of high-intensity interval training and prolonged continuous exercise training on abdominal visceral fat reduction in obese young women. J Diabetes Res 2017;2017:5071740.
crossref pmid pmc pdf
27. Ohyama K, Nogusa Y, Suzuki K, Shinoda K, Kajimura S, Bannai M. A combination of exercise and capsinoid supplementation additively suppresses diet-induced obesity by increasing energy expenditure in mice. Am J Physiol - Endocrinol Metab 2015;308:E315-23.
crossref pmid
28. Shin KO, Moritani T. Alterations of autonomic nervous activity and energy metabolism by capsaicin ingestion during aerobic exercise in healthy men. J Nutr Sci Vitaminol (Tokyo) 2007;53:124-32.
crossref pmid
29. Yoshioka M, Matsuo T, Lim K, Tremblay A, Suzuki M. Effects of capsaicin on abdominal fat and serum free-fatty acids in exercise-trained rats. Nutr Res 2000;20:1041-5.
crossref
30. Medina-Contreras JML, Colado-Velázquez J, Gómez-Viquez NL, Mailloux-Salinas P, Pérez-Torres I, Aranda-Fraustro A, Carvajal K, Bravo G. Effects of topical capsaicin combined with moderate exercise on insulin resistance, body weight and oxidative stress in hypoestrogenic obese rats. Int J Obes 2017;41:750-8.
crossref pdf
31. Kim J, Park J, Lim K. Nutrition supplements to stimulate lipolysis: a review in relation to endurance exercise capacity. J Nutr Sci Vitaminol (Tokyo) 2016;62:141-61.
crossref pmid
32. Kim J, Hwang H, Park J, Yun HY, Suh H, Lim K. Silk peptide treatment can improve the exercise performance of mice. J Int Soc Sports Nutr 2014;11:35.
crossref pmid pmc
33. Iwai K, Yazawa A, Watanabe T. Roles as metabolic regulators of the non-nutrients, capsaicin and capsiate, supplemented to diets. Proc Japan Acad Ser B 2003;79:207-12.
crossref
34. Hachiya S, Kawabata F, Ohnuki K, Inoue N, Yoneda H, Yazawa S, Fushiki T. Effects of CH-19 Sweet, a non-pungent cultivar of red pepper, on sympathetic nervous activity, body temperature, heart rate, and blood pressure in humans. Biosci Biotechnol Biochem 2007;71:671-6.
crossref pmid
35. Nedergaard J, Golozoubova V, Matthias A, Asadi A, Jacobsson A, Cannon B. UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefciency. Biochim Biophys Acta 2001;1504:82-106.
crossref pmid
36. Holm C. Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem Soc Trans 2003;31:1120-4.
crossref pmid pdf
37. Hong Q, Xia C, Xiangying H, Quan Y. Capsinoids suppress fat accumulation via lipid metabolism. Mol Med Rep 2015;11:1669-74.
crossref pmid
38. Masuda Y, Haramizu S, Oki K, Ohnuki K, Watanabe T, Yazawa S, Kawada T, Hashizume S, Fushiki T. Upregulation of uncoupling proteins by oral administration of capsiate, a nonpungent capsaicin analog. J Appl Physiol 2003;95:2408-15.
crossref pmid
39. McGlinchy SA. The effect of two high intensity interval training protocols on heart rate, caloric expenditure, and substrate utilization during exercise and recovery. [master's thesis]. Ohio: UToledo; 2012.

40. Sigal RJ, Kenny GP, Boulé NG, Wells GA, Prud’homme D, Fortier M, Reid RD, Tulloch H, Coyle D, Phillips P, Jennings A, Jaffey H. Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial. Ann Intern Med 2007;147:357-69.
crossref pmid
41. Ku YH, Han KA, Ahn H, Kwon H, Koo BK, Kim HC, Min KW. Resistance exercise did not alter intramuscular adipose tissue but reduced retinol-binding protein-4 concentration in individuals with type 2 diabetes mellitus. J Int Med Res 2010;38:782-91.
crossref pmid


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