본문 바로가기
KERD
논문KCI 등재

저강도 운동이 고지방식이로 유도된 비만 쥐의 지방세포에서 염증반응 및 세포사멸에 미치는 영향

The Effect of Low Intensity Exercise on Expression of Inflammatory Response and Apoptosis in Rats with Obesity Induced by a High-Fat Diet

2

조회

0

다운로드

4

인용

0

참고문헌

키워드

초록

PURPOSE: The goal of this study is to demonstrate whether low intensity exercise has an effect on the level of inflammatory response and apoptosis in rats with obesity induced by a high-fat diet. METHODS: A high fat diet (60% fat, 20% carbohydrate, and 20% protein) was treated to a subset of experimental rats for 35 weeks to induce obesity before exercise intervention. The rats were randomly assigned into 3 groups: normal control (ND-CON, n=7), High- Fat Diet control (HFD-CON, n=7) and High-Fat Diet+Exercise (HFD-EXE, n=7). The low intensity exercise program was performed for 10 weeks with treadmill (30 min/day, 5 days/week). After treadmill exercise, body weight, total fat mass, HOMA-IR and OGTT were analyzed. Also TLR-4 signaling pathway related proteins, inflammation related factors and apoptosis were analyzed using Western blot method. RESULTS: Low intensity exercise with treadmill reduces body weight and body fat of obese rats that were induced by high fat diet, and improves insulin resistance and blood glucose recovery ability. In addition, low intensity exercise inhibits the activity of NF-κB by reducing TLR4 protein, which regulates inflammation and immunity. This has shown to reduce the inflammatory cytokines IL-1β and TNF-α, Bax and Caspase3 proteins associated with apoptosis, and improve Bcl2 protein. CONCLUSIONS: In conclusion, low intensity exercise reduces the level of TLR4 protein that regulates immune and inflammatory responses in adipocytes of obese rats induced by high fat diet. This inhibits the activity of inflammatory cytokines and apoptosis-related proteins, which will be effective in the prevention and treatment of obesity.

Abstract

PURPOSE: The goal of this study is to demonstrate whether low intensity exercise has an effect on the level of inflammatory response and apoptosis in rats with obesity induced by a high-fat diet. METHODS: A high fat diet (60% fat, 20% carbohydrate, and 20% protein) was treated to a subset of experimental rats for 35 weeks to induce obesity before exercise intervention. The rats were randomly assigned into 3 groups: normal control (ND-CON, n=7), High- Fat Diet control (HFD-CON, n=7) and High-Fat Diet+Exercise (HFD-EXE, n=7). The low intensity exercise program was performed for 10 weeks with treadmill (30 min/day, 5 days/week). After treadmill exercise, body weight, total fat mass, HOMA-IR and OGTT were analyzed. Also TLR-4 signaling pathway related proteins, inflammation related factors and apoptosis were analyzed using Western blot method. RESULTS: Low intensity exercise with treadmill reduces body weight and body fat of obese rats that were induced by high fat diet, and improves insulin resistance and blood glucose recovery ability. In addition, low intensity exercise inhibits the activity of NF-κB by reducing TLR4 protein, which regulates inflammation and immunity. This has shown to reduce the inflammatory cytokines IL-1β and TNF-α, Bax and Caspase3 proteins associated with apoptosis, and improve Bcl2 protein. CONCLUSIONS: In conclusion, low intensity exercise reduces the level of TLR4 protein that regulates immune and inflammatory responses in adipocytes of obese rats induced by high fat diet. This inhibits the activity of inflammatory cytokines and apoptosis-related proteins, which will be effective in the prevention and treatment of obesity.

참고문헌 (56)

  1. Victoria JV, "Effects of diet and exercise on metabolic disturbances in high-fat diet-fed mice", Cytokine, 46(3), pp.339~345 (2009)
  2. Dandona P, "Inflammation : the link between insulin resistance, obesity and diabetes", Trends Immunol, 25(1), pp.4~7 (2004)
  3. Despres, JP, "Intra-addominalobesity : An untreated risk factor for type 2 diabetes and cardiovascular disease", J Endocrinol Invest, 29(3), pp.77~82 (2006)
  4. Jung GH, "The Relationships between Serum Adipokines and Cardiovascular Risk Factors in Metabolic Syndrome", pp.2007
  5. Schaffler A, "Role of adipose tissue as an inflammatory organ in human diseases", Endocr Rev, 27(5), pp.449~467 (2006)
  6. Mohamed-Ali V, "Adipose tissue as an endocrine and paracrine organ", Int J Obes Relat Metab Disord, 22(12), pp.1145~1158 (1998)
  7. Engeli s, "Physiology and pathophysiology of the adipose tissue renin-angiotensin system", Hypertension, 35(6), pp.1270~1277 (2000)
  8. Shapiro ME, "Effects of treatment of C57BL", 6j mice fed high vs. low fat diets with metformin or rosiglitazone on adiposity, food intake, hyperglycemia and insulin resistance, 2001, ~
  9. Villareal DT, "Physical frailty and body composition in obese elderly men and women", Obes Res, 12(6), pp.913~920 (2004)
  10. Visser M, "Elevated C-reactive protein levels in overweight and obese adults", JAMA, 282(22), pp.2131~2135 (1999)
  11. Bjorkbacka H, "Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways", Nat Med, 10(4), pp.416~421 (2004)
  12. Song MJ, "Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes", Biochem Biophys Res Commun, 346(3), pp.739~745 (2006)
  13. Schaffler A, "Adipose tissue as an immunological organ : Toll-like receptors, C1q", TNFs and CTRPs, 2007, pp.28(9), 393~399
  14. Rosa JC, "Exhaustive exercise increases inflammatory response via Toll like receptor-4and NF-κBp65 pathway in rat adipose tissue", J Cell Physiol, 226(6), pp.1604~1607 (2011)
  15. Medzhitov R, "A human homologue of the Drosophila Toll protein signals activation of adaptive immunity", Nature, 388(6640), pp.394~397 (1997)
  16. Sabroe I, "Toll-like receptors in health and disease : complex questions remain", J Immunol, 171(4), pp.1630~1635 (2003)
  17. Biragyn A, "Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2", Science, 298(5595), pp.1025~1029 (2002)
  18. Oliveira JL, "Hydrogenated fat intake during pregnancy and lactation caused increase in TRAF-6 and reduced AdipoR1 in white adipose tissue, but not in muscle of 21 days old offspring rats", Lipids Health Dis, 10(1), pp.22~ (2011)
  19. Carmody RJ, "Nuclear factor-kappaB : activation and regulation during toll-like receptor signaling", Cell Mol Immunol, 4(1), pp.31~41 (2007)
  20. Takeda K, "Toll-like receptors in innate immunity", Int Immunol, 17(1), pp.1~14 (2005)
  21. Ho RC, "Regulation of IkappaB kinase and NF-kappaB in contracting adult ratskeletal muscle", Am J Physiol Cell Physiol, 289(4), pp.794~801 (2005)
  22. Tang SC, "Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenal", Exp Neurol, 213(1), pp.114~121 (2008)
  23. Li NC, "Aerobic exercise blocks interleukin-6 levels and germ cell apoptosis in obese rats", Andrologia (2017)
  24. Cani PD, "Metabolic endotoxemia initiates obesity and insulin resistance", Diabetes, 56(7), pp.1761~1772 (2007)
  25. 서영성, "고지방 저제지방 비비만 여성에서 전염증성 사이토카인과 인슐린저항성", Diabetes and Metabolism Journal, 31(2), pp.136~143 (2007), 대한당뇨병학회
  26. Poret JM, "High fat diet consumption differentially affects adipose tissue inflammation and adipocyte size in obesity-prone and obesity-resistant rats", Int J Obes, pp.280~ (2017)
  27. Kawanishi N, "Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2macrophages in high-fat-diet-induced obese mice", Exerc Immunol Rev, 16, pp.105~118 (2010)
  28. Li G, "Exercise training attenuates sympathetic activation and oxidative stress in diet-induced obesity", Physiol Res, 64(3), pp.355~367 (2015)
  29. Zhang G, "Swim Training Attenuates Inflammation and Improves Insulin Sensitivity in Mice Fed with a High-Fat Diet", Int J Endocrinol, 2017, pp.5940732~ (2017)
  30. Fischer CP, "Interleukin-6 in acute exercise and training : what is the biological relevance?", Exerc Immunol Rev, 12, pp.6~33 (2006)
  31. Petersen AM, "The anti-inflammatory effect of exercise", J Appl Physiol, 98(4), pp.1154~1162 (2005)
  32. 조도근, "Effect of treadmill exercise on skeletal muscle autophagy in rats with obesity induced by a high-fat diet", Physical Activity and Nutrition, 21(3), pp.26~34 (2017), 한국운동영양학회[DOI]
  33. 최동훈, "The effect of treadmill exercise on inflammatory responses in rat model of streptozotocin-induced experimental dementia of Alzheimer's type", Physical Activity and Nutrition, 18(2), pp.225~233 (2014), 한국운동영양학회
  34. Kim HB, "Treadmill exercise increases cell proliferation in dentate gyrus of rats with streptozotocin-induced diabetes", J Diabetes Complications, 17(1), pp.29~33 (2003)
  35. Luca DC, "Stressed out about obesity and insulin resistance", Nat Med, 12(1), pp.41~42 (2006)
  36. Rao X, "Exercise Protects against Diet-Induced Insulin Resistance through Downregulation of Protein Kinase Cβ in Mice", PLoS One, 8(12), pp.e81364~ (2013)
  37. Delghingaro-Augusto V, "Voluntary running exercise prevents β-cell failure in susceptible islets of the Zucker diabetic fatty rat", Endocrinology and Metabolism-Am J Physiol, 302(2), pp.254~264 (2012)
  38. Hainsworth AH, "Do in vivo experimental models reflect human cerebral small vessel disease? A systematic review", J Cereb Blood Flow Metab, 28(12), pp.1877~1891 (2008)
  39. Holloszy JO, "Adaptations of skeletal muscle mitochondria to endurance exercise : a personal perspective", Exerc Sport Sci Rev, 32(2), pp.41~43 (2004)
  40. Kim JK, "Metabolic impairment precedes insulin resistance in skeletal muscle during high-fat feeding in rats", Diabetes, 45(5), pp.651~658 (1996)
  41. Vitseva OI, "Inducible Toll-like receptor and NF-kappaB regulatory pathway expression in human adipose tissue", Obesity(Silver Spring), 16(5), pp.932~937 (2008)
  42. Suganami T, "Role of the Toll-like receptor 4", NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages, 2007, pp.27(1), 84~91
  43. Shi H, "TLR4 links innate immunity and fatty acid-induced insulin resistance", J Clin Invest, 116(11), pp.3015~3025 (2006)
  44. Oliveira AG, "Physical exercise reduces circulating lipopolysaccharide and TLR4 activation and improves insulin signaling in tissues of DIO rats", Diabetes, 60(3), pp.784~796 (2011)
  45. Akira S, "Toll-like receptor signalling", Nat Rev Immunol, 4(7), pp.499~511 (2004)
  46. Hoshino K, "Differential involvement of IFN-β in Toll-like receptorstimulated dendritic cell activation", Int J Immunol, 14(10), pp.1225~1231 (2002)
  47. Kock A, "Human keratinocytes are a source for tumor necrosis factor α : evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light", J Exp Med, 172(6), pp.1609~1614 (1990)
  48. Bankers-Fulbright JL, "Interleukin-1 signal transduction", Life Sci, 59(2), pp.61~83 (1996)
  49. Song MJ, "Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes", Biochem Biophys Res Commun, 346(3), pp.739~745 (2006)
  50. Hotamisligil GS, "Adipose expression of tumor necrosis factor-alpha : direct role in obesity-linked insulin resistance", Science, 259(5091), pp.87~91 (1993)
  51. Francaux M, "Toll-like receptor signalling induced by endurance exercise", Appl Physiol Nutr Metab, 34(3), pp.454~458 (2009)
  52. Lin Y, "The lipopolysaccharide-activated toll-like receptor(TLR)-4 induces synthesis of the closely related receptor TLR-2 in adipocytes", J Biol Chem, 275(32), pp.24255~24263 (2000)
  53. Hawley JA, "Exercise as a therapeutic intervention for the prevention and treatment of insulin resistance", Diabetes Metab Res Rev, 20(5), pp.383~393 (2004)
  54. Fulda S, "Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy", Oncogene, 25(34), pp.4798~4811 (2006)
  55. Adams JM, "The Bcl-2 apoptotic switch in cancer development and therapy", Oncogene, 26(9), pp.1324~1337 (2007)
  56. Hacker G, "BH3-only proteins trigger cytochrome c release, but how?", Arch Biochem Biophys, 462(2), pp.150~155 (2007)

관련 논문AI추천

이 간행물의 다른 논문 (8건)