본문 바로가기
KERD
논문KCI 등재

올레산으로 유도된 비알코올성 지방간 세포 모델에서의 미세전류 자극의 지질 대사 조절 효능 평가

Effects of Micro-current Stimulation on lipid metabolism in Oleic Acid-Induced Non-Alcoholic Fatty Liver disease in FL83B cells

이민주|김한성|이한아
대한의용생체공학회 (The Korea Society Of Medical & Biological Engineering)|2022.02|의공학회지 (Journal of biomedical Engineering Research)|제43권 제1호|pp. 1-10

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

Lipid metabolismNon-alcoholic fatty liver diseaseMicro-current stimulationHepatic lipid accumulationFL83B cells

초록

Non-alcoholic fatty liver disease(NAFLD) is excessive hepatic lipid accumulation mainly caused by obesity. This study aimed to evaluate whether micro-current stimulation(MCS) could modulate lipid metabolism regarding the Sirt1/AMPK pathway, fatty acid β-oxidation pathway, and lipolysis and lipogenesis-related factors in FL83B cells. For the NAFLD cell model, FL83B cells were treated with oleic acid for lipid accumulation. MCS were stimulated for 1 hr and used frequency 10 Hz, duty cycle 50%, and biphasic rectangular current pulse. The intensity of MCS was divided into 50, 100, 200, and 400 μA. Through the results of Oil red O staining, it was confirmed that MCSs with the intensity of 200 μA and 400 μA significantly reduced the degree of lipid droplet formation. Thus, these MCS intensities were applied to western blot analysis. Western blot analysis was performed to analyze the effects of MCS on lipid metabolism. MCS with the intensity of 400 μA showed that significantly activated the Sirt1/AMPK pathway, a key pathway for regulating lipid metabolism in hepatocytes, and fatty acid β-oxidation-related transcription factors. Moreover, it activated the lipolysis pathway and suppressed lipogenesis-related transcription factors such as SREBP- 1c, FAS, and PPARγ. In the case of MCS with the intensity of 200 μA, only PGC1α and SREBP-1c showed significant differences compared to cells treated only with oleic acid. Taken together, these results suggested that MCS with the intensity of 400 μA could alleviate hepatic lipid accumulation by modulating lipid metabolism in hepatocytes.

Abstract

Non-alcoholic fatty liver disease(NAFLD) is excessive hepatic lipid accumulation mainly caused by obesity. This study aimed to evaluate whether micro-current stimulation(MCS) could modulate lipid metabolism regarding the Sirt1/AMPK pathway, fatty acid β-oxidation pathway, and lipolysis and lipogenesis-related factors in FL83B cells. For the NAFLD cell model, FL83B cells were treated with oleic acid for lipid accumulation. MCS were stimulated for 1 hr and used frequency 10 Hz, duty cycle 50%, and biphasic rectangular current pulse. The intensity of MCS was divided into 50, 100, 200, and 400 μA. Through the results of Oil red O staining, it was confirmed that MCSs with the intensity of 200 μA and 400 μA significantly reduced the degree of lipid droplet formation. Thus, these MCS intensities were applied to western blot analysis. Western blot analysis was performed to analyze the effects of MCS on lipid metabolism. MCS with the intensity of 400 μA showed that significantly activated the Sirt1/AMPK pathway, a key pathway for regulating lipid metabolism in hepatocytes, and fatty acid β-oxidation-related transcription factors. Moreover, it activated the lipolysis pathway and suppressed lipogenesis-related transcription factors such as SREBP- 1c, FAS, and PPARγ. In the case of MCS with the intensity of 200 μA, only PGC1α and SREBP-1c showed significant differences compared to cells treated only with oleic acid. Taken together, these results suggested that MCS with the intensity of 400 μA could alleviate hepatic lipid accumulation by modulating lipid metabolism in hepatocytes.

참고문헌 (48)

  1. Gui Y, "The associa-tion between obesity related adipokines and risk of breast cancer: a meta-analysis", Oncotarget, 8(43), pp.75389~ (2017)
  2. 유기덕, "비알코올 지방간 질환의 생활습관 치료", 대한내과학회지, 86(4), pp.416~424 (2014), 대한내과학회[DOI]
  3. Lin HTV, "Effects of low-molecular-weight fucoidan and high stability fucoxanthin on glucose homeostasis, lipid metabolism, and liver function in a mouse model of type II diabetes", Marine drugs, 15(4), pp.113~ (2017)
  4. Kitade H, "Nonalcoholic fatty liver dis-ease and insulin resistance: new insights and potential new treatments", Nutrients, 9(4), pp.387~ (2017)
  5. He XX, "Effectiveness of omega-3 polyunsaturated fatty acids in non-alcoholic fatty liver disease: a meta-analysis of random-ized controlled trials", PLoS One, 11(10), pp.0162368~ (2016)
  6. 김추숙, "유리지방산 유도 지방간세포에서 Isorhamnetin의 PPARα 활성화 작용을 통한 지질 축적 억제 효과", 한국식품영양과학회지, 47(7), pp.703~709 (2018), 한국식품영양과학회
  7. Raghow R, "SREBPs:the crossroads of physiological and pathological lipid homeostasis", Trends in endocrinology & metabolism, 19(2), pp.65~73 (2008)
  8. Yeh YT, "Chinese olive extract ameliorates hepatic lipid accumulation in vitro and in vivo by reg-ulating lipid metabolism", Scientific reports, 8(1), pp.1~13 (2018)
  9. Browning JD, "Molecular mediators of hepatic steatosis and liver injury", The Journal of clinical investigation, 114(2), pp.147~152 (2004)
  10. Tian J, "Insulin induction of SREBP-1c in rodent liver requires LXRα-C", EBPβ complex, 2016, pp.113(29), 8182~8187
  11. Wang Y, "Transcriptional regula-tion of hepatic lipogenesis", Nature reviews Molecular cell biology, 16(11), pp.678~689 (2015)
  12. Long YC, "AMP-activated protein kinase signal-ing in metabolic regulation", The Journal of clinical investi-gation, 116(7), pp.1776~1783 (2006)
  13. Foretz M, "Regulation of hepatic metabolism by AMPK", Journal of Hepatology, 54(4), pp.827~829 (2011)
  14. Li YU, "AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice", Cell metabolism, 13(4), pp.376~388 (2011)
  15. Staels B, "Therapeutic roles of peroxisome pro-liferator–activated receptor agonists", Diabetes, 54(8), pp.2460~2470 (2005)
  16. Szkudelski T, "Effects of AMPK activation on lipolysis in primary rat adipocytes: studies at different glucose concentrations", Archives of physiology and biochemistry, 123(1), pp.43~49 (2017)
  17. Liou CJ, "Fisetin protects against hepatic steatosis through regulation of the Sirt1", AMPK and fatty acid β-oxidation signaling path-way in high-fat diet-induced obese mice, 2018, pp.49(5), 1870~1884
  18. Cho MS, "The effect of microcurrent-inducing shoes on fatigue and pain in mid-dle-aged people with plantar fascitis", Journal of Physical Therapy Science, 19(2), pp.165~170 (2007)
  19. Oh HJ, "The effects of microcurrent stimu-lation on recovery of function and pain in chronic low back pain", Journal of the Korean Society of Physical Medicine, 3(1), pp.47~56 (2008)
  20. 황동현, "Wnt", β-catenin 신호 활성화를 통한 미세전류 자극의 지방생성 억제 효과, 2020, pp.41(6), 235~246[DOI]
  21. 김한성, "세포 전기자극 시스템 및 방법", 대한민국 특허청등록특허공보, ~ (2020)
  22. Reccia I, "Non-alcoholic fatty liver disease: a sign of systemic disease", Metabolism, 72, pp.94~108 (2017)
  23. Hazlehurst JM, "Non-alcoholic fatty liver disease and diabetes", Metabo-lism, 65(8), pp.1096~1108 (2016)
  24. Heindel JJ, "Endocrine disruptors and obesity", Nature Reviews Endocrinology, 11(11), pp.653~661 (2015)
  25. Yoo A, "Scopolin ameliorates high-fat diet induced hepatic steatosis in mice:potential involvement of SIRT1-mediated signaling cascades in the liver", Scientific reports, 7(1), pp.1~11 (2017)
  26. Herbrechter R, "Identification of Glycyrrhiza as the rik-kunshito constituent with the highest antagonistic potential on heterologously expressed 5-HT3A receptors due to the action of flavonoids", Frontiers in pharmacology, 6, pp.130~ (2015)
  27. Wang Z, "Homocysteine suppresses lipolysis in adipocytes by activat-ing the AMPK pathway", American journal of physiology-endocrinology and metabolism, 301(4), pp.703~712 (2011)
  28. Chen H, "Role of SIRT1 and AMPK in mesenchymal stem cells differ-entiation", Ageing research reviews, 13, pp.55~64 (2014)
  29. Lim CT, "AMPK as a mediator of hormonal signalling", Journal of molecular endocrinology, 44(2), pp.87~ (2010)
  30. Peng IC, "Glucagon regulates ACC activity in adipocytes through the CAMKKβ", AMPK pathway, 2012, pp.302(12), 1560~1568
  31. Huang WC, "Phloretin and phlorizin promote lipolysis and inhibit inflam-mation in mouse 3T3-L1 cells and in macrophage-adipocyte co-cultures", Molecular nutrition & food research, 57(10), pp.1803~1813 (2013)
  32. Malandrino MI, "Enhanced fatty acid oxi-dation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation", American Journal of Physiology-Endocrinology and Metabolism, 308(9), pp.756~769 (2015)
  33. Houten SM, "The bio-chemistry and physiology of mitochondrial fatty acid β-oxidation and its genetic disorders", Annual review of physiology, 78, pp.23~44 (2016)
  34. Brunt EM, "Nonalcoholic fatty liver disease: pros and cons of histologic systems of evaluation", International journal of molecu-lar sciences, 17(1), pp.97~ (2016)
  35. Choi SS, "Hepatic triglyceride synthesis and non-alcoholic fatty liver disease", Current opinion in lipidology, 19(3), pp.295~300 (2008)
  36. Cherkaoui-Malki M, "Hepatic steatosis and peroxisomal fatty acid beta-oxidation", Current Drug Metabolism, 13(10), pp.1412~1421 (2012)
  37. Evans RM, "PPARs and the complex journey to obesity", Nature medicine, 10(4), pp.355~361 (2004)
  38. Postic C, "Contribution of de novo fatty acid synthe-sis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice", The Journal of clinical investi-gation, 118(3), pp.829~838 (2008)
  39. Finck BN, "PGC-1 coactivators: inducible regula-tors of energy metabolism in health and disease", The Journal of clinical investigation, 116(3), pp.615~622 (2006)
  40. Day EA, "AMPK as a therapeutic tar-get for treating metabolic diseases", Trends in Endocrinology & Metabolism, 28(8), pp.545~560 (2017)
  41. Smith BK, "Treatment of nonalcoholic fatty liver disease: role of AMPK", American Journal of Physiology-Endocrinology and Metabolism, 311(4), pp.730~740 (2016)
  42. Ducharme NA, "Minireview: lipid droplets in lipo-genesis and lipolysis", Endocrinology, 149(3), pp.942~949 (2008)
  43. Frühbeck G, "Regulation of adipocyte lipolysis", Nutrition research reviews, 27(1), pp.63~93 (2014)
  44. Malandrino MI, "Enhanced fatty acid oxi-dation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation", American Journal of Physiology-Endocrinology and Metabolism, 308(9), pp.756~769 (2015)
  45. Duncan RE, "Regulation of lipolysis in adipocytes", Annu. Rev. Nutr, 27, pp.79~101 (2007)
  46. Lampidonis AD, "The resurgence of Hormone-Sensitive Lipase (HSL) in mamma-lian lipolysis", Gene, 477(1-2), pp.1~11 (2011)
  47. Gaidhu MP, "Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipo-cytes: novel mechanisms integrating HSL and ATGL", Journal of lipid research, 50(4), pp.704~715 (2009)
  48. Li Y, "Resveratrol suppresses the STAT3 signaling pathway and inhibits proliferation of high glucose-exposed HepG2 cells partly through SIRT1", Oncol-ogy reports, 30(6), pp.2820~2828 (2013)

관련 논문AI추천

Wnt/β-catenin 신호 활성화를 통한 미세전류 자극의 지방생성 억제 효과김한성, 이민주, 이한아, 조승관, 황동현대한의용생체공학회 · 의공학회지2020 · 제41권 제6호중만분소환 추출물이 Palmitate로 유발된 비알코올성 지방간 HepG2 cell 모델에 미치는 영향이지원, 전상윤, 최창원, 하예진, 한창우대한한방내과학회 · 대한한방내과학회지2016 · 제37권 제3호동과자 에탄올 추출물이 비알코올성 지방간 세포 모델에 미치는 효과권민정, 김균하, 김소연, 주명수, 최준용, 한창우대한한방내과학회 · 대한한방내과학회지2012 · 제33권 제4호곽향과 금전초 추출물이 Palmitic acid로 유발된 비알코올성 지방간 세포 모델에 미치는 영향김영광, 김은지, 문영호, 이다은, 이혜인, 임현찬대한한방내과학회 · 대한한방내과학회지2018 · 제39권 제3호비알코올성 지방간 세포 모델에서 곤포의 효능과 기전 연구이인, 권민정, 권정남, 김소연, 박성하, 주명수, 최준용, 한창우, 홍진우대한한방내과학회 · 대한한방내과학회지2014 · 제35권 제2호강황 추출물의 비알코올성 지방간 질환 개선 효과강옥화, 권동렬, 이대영, 이영섭한국약용작물학회 · 한국약용작물학회지2020 · 제28권 제4호

이 간행물의 다른 논문 (7건)

세포 및 동물모델용 펄스형 전자기장 자극 파라미터 가변장치 설계 및 평가이자우, 박창순, 이용흠, 김준영pp. 11-18약물의 염전성 부정맥 유발 예측 지표로서 심장의 전기생리학적 특징 값들의 검증정다운, Aroli Marcellinus, 임기무, 유예담pp. 19-26생체 신호 기반 음주량 예측 및 음주량에 따른 운전 능력 평가김태현, 김한성, 최준원, 서정훈, 박승원, 정면규, 이강인pp. 27-34가상경계-격자 볼츠만 방법을 이용한 유동장내 나노/마이크로 입자에 작용하는 힘의 해석이세영, 조홍주pp. 35-44InceptionV3 기반의 심장비대증 분류 정확도 향상 연구정우연, 김정훈pp. 45-51
원문 보기