期刊论文详细信息
Nutrition & Metabolism
Hypothalamic inflammation is reversed by endurance training in anorectic-cachectic rats
Marília Seelaender4  Filippo Rossi-Fanelli3  Alessandro Laviano3  Miguel L Batista4  Ronaldo VT Santos2  Gustavo D Pimentel1  Luiz C Carnevali4  Erico Caperuto4  Fábio L Tavares4  Jose C Rosa1  Alex S Yamashita4  Fábio S Lira1 
[1] Department of Physiology, Division of Nutrition Physiology, Federal University of São Paulo (UNIFESP), São Paulo, SP - Brazil;Department of Bioscience, Federal University of São Paulo, Baixada Santista, Campus, São Paulo, Brazil;Department of Clinical Medicine, Sapienza University of Rome, Rome - Italy;Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP - Brazil
关键词: inflammation;    cytokines;    exercise training;    hypothalamus;    cancer cachexia;    anorexia;   
Others  :  820379
DOI  :  10.1186/1743-7075-8-60
 received in 2011-05-06, accepted in 2011-08-24,  发布年份 2011
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【 摘 要 】

Aim

We tested the effects of a cancer cachexia-anorexia sydrome upon the balance of anti and pro-inflammatory cytokines in the hypothalamus of sedentary or trained tumour-bearing (Walker-256 carcinosarcoma) rats.

Methods

Animals were randomly assigned to a sedentary control (SC), sedentary tumour-bearing (ST), and sedentary pair-fed (SPF) groups or, exercised control (EC), exercised tumour-bearing (ET) and exercised pair-fed (EPF) groups. Trained rats ran on a treadmill (60%VO2max) for 60 min/d, 5 days/wk, for 8 wks. We evaluated food intake, leptin and cytokine (TNF-α, IL1β) levels in the hypothalamus.

Results

The cumulative food intake and serum leptin concentration were reduced in ST compared to SC. Leptin gene expression in the retroperitoneal adipose tissue (RPAT) was increased in SPF in comparison with SC and ST, and in the mesenteric adipose tissue (MEAT) the same parameter was decreased in ST in relation to SC. Leptin levels in RPAT and MEAT were decreased in ST, when compared with SC. Exercise training was also able to reduce tumour weight when compared to ST group. In the hypothalamus, IL-1β and IL-10 gene expression was higher in ST than in SC and SPF. Cytokine concentration in hypothalamus was higher in ST (TNF-α and IL-1β, p < 0.05), compared with SC and SPF. These pro-inflammatory cytokines concentrations were restored to control values (p < 0.05), when the animals were submitted to endurance training.

Conclusion

Cancer-induced anorexia leads towards a pro-inflammatory state in the hypothalamus, which is prevented by endurance training which induces an anti-inflammatory state, with concomitant decrease of tumour weight.

【 授权许可】

   
2011 Lira et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Tisdale MJ: The 'cancer cachectic factor. Support Care Cancer 2003, 11:73-78.
  • [2]Bing C, Taylor S, Tisdale MJ, et al.: Cachexia in MAC16 adenocarcinoma: suppression of hunger despite normal regulation of leptin, insulin and hypothalamic neuropeptide Y. Journal of Neurochemistry 2001, 79:1004-1012.
  • [3]Bing C, Trayhurn P: Regulation of adipose tissue metabolism in cancer cachexia. Current Opinion in Clinical Nutrition & Metabolic Care 2008, 11:201-207.
  • [4]Chen SZ, Qiu ZG: Combined treatment with GH, insulin, and indomethacin alleviates cancer cachexia in a mouse model. Journal of Endocrinology 2011, 208:131-136.
  • [5]Inui A: Cancer anorexia-cachexia syndrome: are neuropeptides the key? Cancer Research 1999, 59:4493-4501.
  • [6]Plata-Salamán CR, Ilyin SE, Gayle D: Brain cytokine mRNAs in anorectic rats bearing prostate adenocarcinoma tumour cells. American Journal Physiology 1998, 275:566-573.
  • [7]Oliff A, Defeo-Jones D, Boyer M, et al.: Tumours secreting human TNF/cachectin induce cachexia in mice. Cell 1987, 50:555-563.
  • [8]Hanahan D, Weinberg RA: Hallmarks of cancer: The next generation. Cell 2011, 144:646-674.
  • [9]Walsh NP, Gleeson M, Shephard RJ, et al.: Position statement. Part one: Immune function and exercise. Exerc Immunol Rev 2011, 17:6-63. Review
  • [10]Lira FS, Rosa JC, Zanchi NE, et al.: Regulation of inflammation in the adipose tissue in cancer cachexia: effect of exercise. Cell Biochem Funct 2009, 27(2):71-5. Review
  • [11]Lira FS, Tavares FL, Yamashita AS, et al.: Effect of endurance training upon lipid metabolism in the liver of cachectic tumour-bearing rats. Cell Biochemistry and Function 2008, 26:701-708.
  • [12]Seelaender MC, Nascimento CM, Curi R, et al.: Studies on the lipid metabolism of Walker 256 tumour-bearing rats during the development of cancer cachexia. Biochemistry & Molecular Biology International 1996, 39:1037-1047.
  • [13]Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analytical Biochemistry 1987, 162:156-159.
  • [14]Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 1976, 7:248-254.
  • [15]Laviano A, Inui A, Marks DL, et al.: Neural control of the anorexia-cachexia syndrome. American Journal Physiology Endocrinology Metabolism 2008, 295:1000-1008.
  • [16]Niswender KD, Morton GJ, Stearns WH, et al.: Intracellular signalling. Key enzyme in leptin-induced anorexia. Nature 2001, 413:794-795.
  • [17]Carvalheira JB, Torsoni MA, Ueno M, et al.: Cross-talk between the insulin and leptin signaling systems in rat hypothalamus. Obes Res 2005, 13:48-57.
  • [18]Flores MB, Fernandes MF, Ropelle ER, et al.: Exercise improves insulin and leptin sensitivity in hypothalamus of Wistar rats. Diabetes 2006, 55:2554-2561.
  • [19]Schwartz MW, Baskin DG, Kaiyala KJ, et al.: Model for the regulation of energy balance and adiposity by the central nervous system. American Journal of Clinical Nutrition 1999, 69:584-596.
  • [20]Machado AP, Costa Rosa LF, Seelaender MC: Adipose tissue in Walker 256 tumour-induced cachexia: possible association between decreased leptin concentration and mononuclear cell infiltration. Cell and Tissue Research 2004, 318:503-514.
  • [21]Pedersen BK: The anti-inflammatory effect of exercise: its role in diabetes and cardiovascular disease control. Essays Biochem 2006, 42:105-17. Review
  • [22]Ardies CM: Exercise, cachexia, and cancer therapy: a molecular rationale. Nutrition Cancer 2002, 42:143-157.
  • [23]Demarzo MM, Martins LV, Fernandes CR, et al.: Exercise reduces inflammation and cell proliferation in rat colon carcinogenesis. Medicine & Science in Sports & Exercise 2008, 40:618-621.
  • [24]Bacurau RF, Belmonte MA, Seelaender MC, et al.: Effect of a moderate intensity exercise training protocol on the metabolism of macrophages and lymphocytes of tumour-bearing rats. Cell Biochemistry and Function 2000, 18:249-258.
  • [25]Dos Santos Cunha WD, Giampietro MV, De Souza DF, et al.: Exercise restores immune cell function in energy-restricted rats. Medicine & Science in Sports & Exercise 2004, 36:2059-2064.
  • [26]Petersen AMW, Pedersen BK: The anti-inflammatory effect of exercise. Journal of Applied Physiology 2005, 98:1154-1162.
  • [27]Polak J, Klimcakova E, Moro C, et al.: Effect of aerobic training on plasma levels and subcutaneous abdominal adipose tissue gene expression of adiponectin, leptin, interleukin 6, and tumour necrosis factor alpha in obese women. Metabolism 2006, 55:1375-1381.
  • [28]Lira F, Rosa J, Yamashita A, et al.: Endurance training induces depot-specific changes in il-10/tnf-α ratio in rat adipose tissue. Cytokine 2009, 45:80-85.
  • [29]Shephard RJ, Verde TJ, Thomas SG, et al.: Physical activity and the immune system. Canadian Journal of Sport Sciences 1991, 16:169-185.
  • [30]Nieman DC: Exercise immunology: practical applications. International Journal of Sports Medicine 1997, 18:91-100.
  • [31]Pedersen BK, Hoffman-Goetz L: Exercise and the immune system: regulation, integration, and adaptation. Physiology Reviews 2000, 80:1055-1081.
  • [32]Sugiura H, Nishida H, Sugiura H, Mirbod SM: Immunomodulatory action of chronic exercise on macrophage and lymphocyte cytokine production in mice. Acta Physiologica Scandinavica 2002, 174:247-256.
  • [33]Chennaoui M, Drogou C, Gomez-Merino D: Effects of physical training on IL-1beta, IL-6 and IL-1ra concentrations in various brain areas of the rat. European Cytokine Network 2008, 19:8-14.
  • [34]Nybo L, Nielsen B, Pedersen BK, et al.: Interleukin-6 release from the human brain during prolonged exercise. Journal Physiology 2002, 542:991-995.
  • [35]Fischer C: Interleukin-6 in acute exercise and training: what is the biological relevance? Exercise Immunology Reviews 2006, 12:6-33.
  • [36]Steensberg A, Fischer C, Keller C, et al.: IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. American Journal Physiology Endocrinology Metabolism 2003, 285:433-437.
  • [37]Costa Rosa L: Exercise as a time-conditioning effector in chronic disease: a complementary treatment strategy. Evidence-based Complementary and Alternative Medicine 2004, 1:63-70.
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