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Anti-Obesity Effects and the Regulation of Energy Metabolism in Skeletal Muscle Tissues of Allii Fistulosi Bulbus Extract in High Fat Diet-Induced Obesity Mice

총백추출물의 고지방식이 유도 비만 마우스에서의 항비만 효과 및 근육조직에서의 에너지대사 조절기전 연구

  • 최윤용 (동국대학교 한의과대학) ;
  • 이현수 (동국대학교 한의과대학) ;
  • 백수연 (동국대학교 한의과대학) ;
  • 임수민 (동국대학교 한의과대학) ;
  • 정효원 (동국대학교 한의과대학) ;
  • 강석용 (동국대학교 한방신약개발센터) ;
  • 박용기 (동국대학교 한의과대학)
  • Received : 2022.10.28
  • Accepted : 2022.11.30
  • Published : 2022.12.30

Abstract

Objectives: We investigated the effects of Allii Fistulosi Bulbus (AFB) on high fat diet (HFD)-induced obesity in mice and the regulation of energy metabolism in muscle tissues of mice. Methods: The C57BL/6 mice (6 weeks, male) were fed a HFD for 8 weeks and then administrated with AFB extract at 500 mg/kg (p.o.) once daily for 4 weeks. The body weight (BW), muscle weight, calorie intake, fasting blood glucose (FBG) and serum glucose, insulin, and low-density lipoprotein-cholesterol (LDL-C) levels were measured in mice. It was also observed the histological changes of pancreas, liver, and fat tissues with hematoxylin and eosin staining. It was investigated the phosphorylation of insulin receptor substrate 1 (IRS-1), Ser/Thr kinase (AKT), and adenosine monophosphate-activated protein kinase (AMPK), and the expression of phosphoinositide 3-kinase, glucose transporter type 4 (GLUT4), and sirtuin1 (Sirt1) in gastrocnemius tissues by western blot, respectively. Results: The increases of BWs, calorie intakes and FBG levels in obesity mice were decreased significantly by the administration of AFB extract. The AFB extract administration was reduced significantly serum levels of glucose, insulin, and LDL-C in obesity mice. The AFB extract inhibited lipid accumulation in liver tissues, hyperplasia of pancreatic islets, and enlargement of fat tissues in obesity mice. The phosphorylation of IRS-1 and AKT was increased significantly in muscle tissues and AMPK phosphorylation and the GLUT4 and Sirt1 expression were decreased significantly in muscle tissues after the AFB administration. Conclusions: Our study indicates that AFB extract improves symptoms of obesity through regulation of energy regulating proteins in muscle tissues.

Keywords

Acknowledgement

이 논문은 2020년도 한국연구재단 '박사후연수지원사업'의 연구비 지원으로 수행되었음(NRF-2020R1A6A3A01099936).

References

  1. Korean Society for the Study of Obesity. Obesity diagnosis [Internet]. Seoul [cited 2022 Oct 17]. Available from: http://general.kosso.or.kr/html/?pmode=obesityDiagnosis.
  2. Korean Society for the Study of Obesity. Quick reference guideline. Seoul : Korean Society for the Study of Obesity. 2020 : x, 58.
  3. Korea Iistitute of Oriental Medicine and the Society of Korean Medicine for Obesity Research. Obesity Korean medicine clinical practice guideline. Daejeon : Korea Iistitute of Oriental Medicine and the Society of Korean Medicine for Obesity Research. 2016.
  4. The Association of Korean Medicine. A variety of treatments [Internet]. 2009 [cited 2002 Oct 17]. Available from: https://www.akom.org/Home/AkomArticleHealth/105320?HealthType=3.
  5. Textbook Compilation Committee of National University of Korean Medicine, Korea. Herbology. Seoul : Younglimsa. 2018 : 174.
  6. Seo YJ. A study on the gynecologic use of Allii Fistulosi Bulbus in Donguibogam. J Orient Obstet Gynecol. 2011 ; 24(1) : 63-73.
  7. Terao J, Hiwada M, Taguchi K, Takahara K, Mohri S. Glutathione peroxidase mimics as novel antioxidants from vegetables. Biofactors. 2005 ; 23(1) : 1-6. https://doi.org/10.1002/biof.5520230101
  8. Phaya N, Higashiyamaa T, Tsujib M, Matsuuraa H, Fukushic Y, Yokotaa A, et al. An antifungal compound from roots of Welsh onion. Phytochemistry. 1999 ; 52(2) : 271-4. https://doi.org/10.1016/S0031-9422(99)00170-3
  9. Ueda H, Takeuchi A, Wako T. Activation of immune responses in mice by an oral administration of bunching onion (Allium fistulosum) mucus. Biosci Biotechnol Biochem. 2013 ; 77(9) : 1809-13. https://doi.org/10.1271/bbb.130084
  10. Chen JH, Chen HI, Wang JS, Tsai SJ, Jen CJ. Effects of Welsh onion extracts on human platelet function in vitro. Life Sci. 2000 ; 66(17) : 1571-9. https://doi.org/10.1016/S0024-3205(00)00477-X
  11. He B, Hao J, Sheng W, Xiang Y, Zhang J, Zhu H, et al. Fistular onion stalk extract exhibits anti-atherosclerotic effects in rats. Exp Ther Med. 2014 ; 8(3) : 785-92. https://doi.org/10.3892/etm.2014.1790
  12. Kang MJ, Kim JH, Choi HN, Kim MJ, Han JH, Lee JH, et al. Hypoglycemic effects of Welsh onion in an animal model of diabetes mellitus. Nutr Res Pract. 2010 ; 4(6) : 486-91. https://doi.org/10.4162/nrp.2010.4.6.486
  13. Shim SB, Ko BS, Ryuk JA, Lee JH, Lee HB, Chan HK, et al. Randomized, double-blind, and placebo-controlled human trial to evaluate the efficacy and safety of Allium Fistulosum L. root extract on improvement of child height growth: study protocol. J Pediatr Korean Med. 2021 ; 35(2) : 11-20. https://doi.org/10.7778/JPKM.2021.35.2.11
  14. Lee CJ, Kim MJ, An SJ. Current treatments on obesity. Korean J Health Promot. 2019 ; 19(4) : 171.
  15. Korean Society for the Study of Obesity. 2021 obesity fact sheet. Seoul : Korean Society for the Study of Obesity. 2021 : 10-3.
  16. Apovian CM, Okemah J, O'Neil PM. Body weight considerations in the management of type 2 diabetes. Adv Ther. 2019 ; 36(1) : 44-58. https://doi.org/10.1007/s12325-018-0824-8
  17. Dambha-Miller H, Day AJ, Strelitz J, Irving G, Griffin SJ. Behaviour change, weight loss and remission of type 2 diabetes: a community-based prospective cohort study. Diabet Med. 2020 ; 37(4) : 681-8. https://doi.org/10.1111/dme.14122
  18. National Health Insurance Service. Health insurance obesity (E66) medical expenses [serial online]. 2020 [cited 2021 Aug 4]. Available from: https://www.docdocdoc.co.kr/news/articleView.html?idxno=2003363.
  19. Son JW. Recent advances in anti-obesity drugs. J Korean Diabetes. 2022 ; 23(2) : 113-27. https://doi.org/10.4093/jkd.2022.23.2.113
  20. Garvey WT. New horizons. A new paradigm for treating to target with second-generation obesity medications. J Clin Endocrinol Metab. 2022 ; 107(4) : e1339-47. https://doi.org/10.1210/clinem/dgab848
  21. Kuryszko J, Slawuta P, Sapikowski G. Secretory function of adipose tissue. Pol J Vet Sci. 2016 ; 19(2) : 441-6. https://doi.org/10.1515/pjvs-2016-0056
  22. Byun S, Lee CH, Jeong H, Kim H, Kwon HM, Park S, et al. Loss of adipose TET proteins enhances β-adrenergic responses and protects against obesity by epigenetic regulation of β3-AR expression. Proc Natl Acad Sci USA. 2022 ; 119(26) : e2205626119.
  23. Ferrulli A, Terruzzi I, Senesi P, Succi M, Cannavaro D, Luzi L. Turning the clock forward: new pharmacological and non pharmacological targets for the treatment of obesity. Nutr Metab Cardiovasc Dis. 2022 ; 32(6) : 1320-34. https://doi.org/10.1016/j.numecd.2022.02.016
  24. Han KS, Lee MJ, Kim HJ. Systematic review on herbal treatment for obesity in adults. J Korean Med Rehabil. 2016 ; 26(4) : 23-35. https://doi.org/10.18325/JKMR.2016.26.4.23
  25. Lim SY. Clinical study of Gambitang for 22 obese patients. J East-West Med. 2011 ; 36(4) : 51-7.
  26. The Society of Korean Medicine Rehabilitaion. Korean rehabilitation medicine. Seoul : Koonja Publisher. 2005 : 349-59.
  27. Farrington R, Musgrave IF, Byard RW. Evidence for the efficacy and safety of herbal weight loss preparations. J Integr Med. 2019 ; 17(2) : 87-92. https://doi.org/10.1016/j.joim.2019.01.009
  28. Hwang MJ, Shin HD, Song MY. Literature review of herbal medicines on treatment of obesity since 2000 - mainly about Ephedra Herba. J Korean Med Obes Res. 2007 ; 7(1) : 39-54.
  29. Sohn HY, Kum EJ, Ftyu HY, Jeon SJ, Kim NS, Son KH. Antifungal activity of fistulosides, steroidal saponins, from allium fistulosum L. J Life Sci. 2006 ; 16(2) : 310-4. https://doi.org/10.5352/jls.2006.16.2.310
  30. Kim HW, Kim BS, Kim YE, Ko SH. Development of extraction method for Welsh onion root by Alliinase activation. Food Eng Prog. 2015 ; 19(2) : 117-21. https://doi.org/10.13050/foodengprog.2015.19.2.117
  31. Tigu AB, Moldovan CS, Toma VA, Farcas AD, Mot AC, Jurj A, et al. Phytochemical analysis and in vitro effects of Allium fistulosum L. and Allium sativum L. extracts on human normal and tumor cell lines: a comparative study. Molecules. 2021 ; 26(3) : 574.
  32. Shi X, Zhou X, Chu X, Wang J, Xie B, Ge J, et al. Allicin improves metabolism in high-fat diet-induced obese mice by modulating the gut microbiota. Nutrients. 2019 ; 11(12) : 2909.
  33. Caballero B. Humans against obesity: who will win? Adv Nutr. 2019 ; 10(suppl_1) : S4-S9. https://doi.org/10.1093/advances/nmy055
  34. Choi CS. Review: pathogenesis of insulin resistance. Korean J Med. 2009 ; 77(2) : 171-7.
  35. Korean Diabetsa Association. Clinical practice guidelines for diabetes. Seoul : Korean Diabetsa Association. 2022 : 11-2, 27-9.
  36. Kim HG, Han JM. Obesity and pancreatic diseases. Korean J Gastroenterol. 2012 ; 59(1) : 35-9. https://doi.org/10.4166/kjg.2012.59.1.35
  37. Kusminski CM, Ghaben AL, Morley TS, Samms RJ, Adams AC, An Y, et al. A novel model of diabetic complications: adipocyte mitochondrial dysfunction triggers massive β-cell hyperplasia. Diabetes. 2020 ; 69(3) : 313-30. https://doi.org/10.2337/db19-0327
  38. Shim JJ. Secondary causes of fatty liver. Single Topic Symposium. 2018 ; 2 : 16-22.
  39. Milic S, Lulic D, Stimac D. Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations. World J Gastroenterol. 2014 ; 20(28) : 9330-7. https://doi.org/10.3748/wjg.v20.i28.9330
  40. Bailey CJ. Metformin: historical overview. Diabetologia. 2017 ; 60(9) : 1566-76. https://doi.org/10.1007/s00125-017-4318-z
  41. Ha JH, Lee SS. Role of AMPK in the regulation of cellular energy metabolism. Endocrinol Metab. 2010 ; 25(1) : 9-17.
  42. Masarwa R, Brunetti VC, Aloe S, Henderson M, Platt RW, Filion KB. Efficacy and safety of metformin for obesity: a systematic review. Pediatrics. 2021 ; 147(3) : e20201610.
  43. Maniar K, Moideen A, Bhattacharyya R, Banerjee D. Metformin exerts anti-obesity effect via gut microbiome modulation in prediabetics: a hypothesis. Med Hypotheses. 2017 ; 104 : 117-20. https://doi.org/10.1016/j.mehy.2017.06.001
  44. Grandone A, Di Sessa A, Umano GR, Toraldo R, Miraglia Del Giudice E. New treatment modalities for obesity. Best Pract Res Clin Endocrinol Metab. 2018 ; 32(4) : 535-49. https://doi.org/10.1016/j.beem.2018.06.007
  45. McCreight LJ, Bailey CJ, Pearson ER. Metformin and the gastrointestinal tract. Diabetologia. 2016 ; 59(3) : 426-35. https://doi.org/10.1007/s00125-015-3844-9
  46. Flory J, Lipska K. Metformin in 2019. JAMA. 2019 ; 321(19) : 1926-7. https://doi.org/10.1001/jama.2019.3805
  47. Swiderska E, Strycharz J, Wroblewski A, Szemraj J, Drzewoski J, Sliwinska A. Role of PI3K/AKT pathway in insulin-mediated glucose uptake. In: Szablewski L, editor. Blood glucose levels. London : IntechOpen. 2018 : 37-54.
  48. Habegger KM, Hoffman NJ, Ridenour CM, Brozinick JT, Elmendorf JS. AMPK enhances insulin-stimulated GLUT4 regulation via lowering membrane cholesterol. Endocrinology. 2012 ; 153(5) : 2130-41. https://doi.org/10.1210/en.2011-2099
  49. Yu BL, Zhao SP, Hu JR. Cholesterol imbalance in adipocytes: a possible mechanism of adipocytes dysfunction in obesity. Obes Rev. 2010 ; 11(8) : 560-7. https://doi.org/10.1111/j.1467-789X.2009.00699.x
  50. Yuan Y, Cruzat VF, Newsholme P, Cheng J, Chen Y, Lu Y. Regulation of SIRT1 in aging: roles in mitochondrial function and biogenesis. Mech Ageing Dev. 2016 ; 155 : 10-21. https://doi.org/10.1016/j.mad.2016.02.003
  51. Wang G, Yu Y, Cai W, Batista TM, Suk S, Noh HL, et al. Muscle-specific insulin receptor overexpression protects mice from diet-induced glucose intolerance but leads to postreceptor insulin resistance. Diabetes. 2020 ; 69(11) : 2294-309. https://doi.org/10.2337/db20-0439
  52. Yaspelkis BB 3rd, Kvasha IA, Figueroa TY. High-fat feeding increases insulin receptor and IRS-1 coimmunoprecipitation with SOCS-3, IKKα/β phosphorylation and decreases PI-3 kinase activity in muscle. Am J Physiol Regul Integr Comp Physiol. 2009 ; 296(6) : R1709-15. https://doi.org/10.1152/ajpregu.00117.2009
  53. Collino M, Mastrocola R, Nigro D, Chiazza F, Aragno M, D'Antona G, et al. Variability in myosteatosis and insulin resistance induced by high-fat diet in mouse skeletal muscles. Biomed Res Int. 2014 ; 2014 : 569623.