The Journal of Internal Korean Medicine (대한한방내과학회지)

The Society of Internal Korean Medicine (대한한방내과학회)
권호 표지

Effect of Acupuncture on the Expressions of Neuropeptide Y and Leptin Receptor in the Hypothalamus of Food-deprived Rats

침치료가 굶긴 쥐 시상하부에서 neuropeptide Y(NPY)와 leptin receptor(LR)의 발현에 미치는 영향에 대한 실험적 연구

  • Kim, Mi-A (Dept. of Cardiovascular and Neurologic Diseases(Stroke center), College of Oriental Medicine, Kyung-Hee University) ;
  • Jung, Woo-Sang (Dept. of Cardiovascular and Neurologic Diseases(Stroke center), College of Oriental Medicine, Kyung-Hee University) ;
  • Moon, Sang-Kwan (Dept. of Cardiovascular and Neurologic Diseases(Stroke center), College of Oriental Medicine, Kyung-Hee University) ;
  • Kim, Young-Suk (Dept. of Cardiovascular and Neurologic Diseases(Stroke center), College of Oriental Medicine, Kyung-Hee University) ;
  • Kim, Chang-Ju (Dept. of physiology, college of Medicine, Kyung-Hee University) ;
  • Cho, Ki-Ho (Dept. of Cardiovascular and Neurologic Diseases(Stroke center), College of Oriental Medicine, Kyung-Hee University)
  • 김미아 (경희대학교 한의과대학 한방순환신경내과학 교실) ;
  • 정우상 (경희대학교 한의과대학 한방순환신경내과학 교실) ;
  • 문상관 (경희대학교 한의과대학 한방순환신경내과학 교실) ;
  • 김영석 (경희대학교 한의과대학 한방순환신경내과학 교실) ;
  • 김창주 (경희대학교 의과대학 생리학교실) ;
  • 조기호 (경희대학교 한의과대학 한방순환신경내과학 교실)
  • Published : 2013.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives : This study aimed to find out whether acupuncture at various acupoints shows any effects on appetite by regulating neurotransmitters in the hypothalamus through the expression of NPY and LR in the PVN via immunohistochemistry. Methods : Male Sprague-Dawley rats were divided into eight groups of five mice each. The rats in the acupuncture groups were treated with acupuncture at respective acupoints, twice per a day for 3 days. The animals were sacrificed 72 h after commencement of the experiment, the brains being dissected into serial coronal sections. Expressions of neuropeptide Y and leptin receptor in the hypothalamus were assessed by immunohistochemistry. Results : NPY expression in the PVN was enhanced and LR expression in the PVN was decreased by food deprivation. NPY immunoreactivity in the PVN of the food-derived rats was decreased by acupuncture at the auricular acupoint, Zusanli-acupoint, a and non-acupoint. However, acupuncture at the auricular acupoint showed most potent suppressing effect on NPY expression in the PVN of food-deprived rats. LR expression in the PVN decreased following food deprivation, and auricular acupuncture increased LR expression in the PVN of food-deprived rats. In normal conditions (fed state), LR expression in the PVN was not changed by acupuncture treatment at several sites. Conclusions : From this study, we have shown that acupuncture at the auricular acupoint exerts the most potent appetite suppressing effect on the food restriction state.

목 적 : 본 연구에서는 침치료가 비만치료의 주요방법인 식욕억제에 효과적인지 알아보기 위하여 굶긴 쥐 시상하부에서 NPY와 LR의 발현 변화를 실험을 통하여 연구하였다. 방 법 : 생후 6주 Sprague-Dawley rats를 한 군에 다섯 마리씩 배정하여 대조군-무치료, 대조군-이침치료, 대조군-족삼리치료, 대조군-임의혈치료, 실험군-무치료, 실험군-이침치료, 실험군-족삼리치료, 실험군-임의혈치료의 8군으로 분류하여 실험하였다. 실험군은 3일간 물만 공급하고 사료를 금식시켰고, 침자극은 하루 2회 3일간 시행하였다. 침은 직경 0.3 mm 이었고, 양측혈을 사용하였고, 2-4 mm 깊이로 자입 하였으며, 20분 유침하였다. 3일 후 pentobarbital로 마취하여 사망시켰고, 4% paraformaldehyde로 조직을 고정한 후 뇌조직을 관상으로 $40{\mu}m$두께로 잘랐다. 식욕조절중후인 시상하부의 paraventricular nucleus(PVN)에서 NPY와 LR의 발현을 면역조직법으로 보았다. 결 과 : 굶기지 않은 대조군에 비하여 굶긴 실험군에서 시상하부 PVN 에서 NPY의 증가와 LR 감소가 나타났다. 굶긴 실험군에 이침, 족삼리, 임의혈 자침시 시상하부 PVN 에서 NPY의 감소가 나타났으며, 이침이 타침 자침에 비하여 NPY의 감소를 더욱 크게 나타냈다. 굶기지 않은 정상상태에서 이침, 족삼리, 임의혈 자침시 NPY의 증가가 있었으며 이는 자침에 의한 스트레스로 인한 것으로 보여진다. 굶긴 실험군에 이침 자침 시에만 시상하부 PVN에서 LR의 증가가 있었으며 정상상태에서 자침시 LR 발현의 변화는 없었다. 결 론 : 이상의 연구결과로서 이침치료가 식욕을 억제하는데 가장 유의한 효과가 있는 것으로 나타났다.

Keywords

References

  1. Cho ZH, Chung SC, Jones JP, Park JB, Park HJ, Lee HJ. New Endings of the correlation between acupoints and corresponding brain cortices using functional MRI. Natl Acad Sci USA 1998;95:2670-3. https://doi.org/10.1073/pnas.95.5.2670
  2. Kim EH, Kim YJ, Lee HJ, Huh Y, Chung JH, Seo JC. Acupuncture increases cell proliferation in dentate gyrus after transient global ischemia in gerbils. Neurosci Lett 2001;297:21-4. https://doi.org/10.1016/S0304-3940(00)01656-6
  3. Kim JH, Min BI, Schmidt D, Lee HJ, Park DS. The difference between electro- acupuncture only and electroacupuncture with manipulation on analgesia in rats. Neurosci Lett 2000;279 :149-52. https://doi.org/10.1016/S0304-3940(99)00994-5
  4. Shiraishi T, Onoe M, Kojima T, Sameshima Y, Kageyama T. Effects of auricular stimulation on feeding-related hypothalamic neuronal activity in normal and obese rats. Brain res bull 1995; 36:141-8. https://doi.org/10.1016/0361-9230(94)00179-5
  5. Tian D, Li X, Niu D, Shi Y, Chang JK, Han J. Electroacupuncture up-regulated arcuate nucleus alpha-MSH expression in the rat of diet-induced obesity. Beijing Daxue Xueba 2003;35:458-61.
  6. Tian DR, Li XD, Wang F, Niu DB, He QH, Li YS, et al. Up-regulation of the expression of cocaine and amphetamine- regulated transcript peptide by electroacupuncture in the arcuate nucleus of diet-induced obese rats. Neurosci Lett 2005;383:17-21. https://doi.org/10.1016/j.neulet.2005.03.039
  7. Chronwall BM, DiMaggio DA, Massari VJ, Pickel VM, Ruggiero DA, O'Donohue TL. The anatomy of neuropeptide-Y-containing neurons in rat brain. Neuroscience 1985;15:1159-81. https://doi.org/10.1016/0306-4522(85)90260-X
  8. Inui A. Feeding and body-weight regulation by hypothalamic neuropeptides-mediation of the actions of leptin. Trends Neurosci 1999;22:62-7. https://doi.org/10.1016/S0166-2236(98)01292-2
  9. O'Donohue TL, Chronwall BM, Pruss RM, Mezey E, Kiss JZ, Eiden LE, et al. Neuropeptide Y and peptide YY neuronal and endocrine systems. Peptides 1985;6:755-68. https://doi.org/10.1016/0196-9781(85)90180-9
  10. Stanley BG, Magdalin W, Seira EA, Nguyen MM, Leibowitz SF. Evidence for neuropeptide Y mediation of eating produced by food deprivation and for a variant of the Y1 receptor mediating this peptide's effect. Peptides 1992;13:581-7. https://doi.org/10.1016/0196-9781(92)90093-I
  11. Brady LS, Smith MA, Gold PW, Herkenham M. Altered expression of hypothalamic neuropeptide mRNAs in food-restricted and food-deprived rats. Neuroendocrinology 1990;52:441-7. https://doi.org/10.1159/000125626
  12. Billington CJ, Briggs JE, Grace M, Levine AS. Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism. Am j Physiol 1991;260:R321-7.
  13. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-32. https://doi.org/10.1038/372425a0
  14. Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2000;404:661-71.
  15. Bear MF, Connors BW, Paradiso MA. Neuroscience: Exploring the Brain. Lippincott Williams & Wilkins 2001.
  16. Ahima RS, Osei, SY. Leptin signaling. Physiol Behav 2004;81:223-41. https://doi.org/10.1016/j.physbeh.2004.02.014
  17. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, et al. Identification and expression cloning of a leptin receptor, Ob-R. Cell 1995;83:1263-71. https://doi.org/10.1016/0092-8674(95)90151-5
  18. Hakansson ML, Brown H, Ghilardi N, Skoda RC, Meister B. Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. J Neurosci 1998;18:559-72.
  19. Ghilardi N, Ziegler S, Wiestner A, Stoffel R, Heim MH, Skoda RC. Defective STAT signaling by the leptin receptor in diabetic mice. Natl Acad Sci USA 1996;93:6231-5. https://doi.org/10.1073/pnas.93.13.6231
  20. Spanswick D, Smith MA, Groppi VE, Logan SD, Ashford ML. Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels. Nature 1997;390:521-5. https://doi.org/10.1038/37379
  21. Shiraishi T, Onoe M, Kageyama T, Sawatsugawa S, Sakurai K. Effects of bilateral auricular acupuncture stimulation on body weight in healthy volunteers and mildly obese patients. Exp Biol Med 2003;228:1201-7.
  22. Emond M, Ladenheim EE, Schwartz GJ, Moean TH. Leptin amplifies the feeding inhibition and neural activation arising from a gastric nutrient preload. Physiol Behav 2001;72:123-8. https://doi.org/10.1016/S0031-9384(00)00393-0
  23. Lee JD, Jang MH, Kim EW, Kim CJ. Acupuncture decreases neuropeptide Y expression in the hypothalamus of rats with streptozotocin-induced diabetes. Acupunct Electrother Res 2004;29:73-82.
  24. Conrad CD, McEwen BS. Acute stress increases neuropeptide Y mRNA within the arcuate nucleus and hilus of the dentate gyrus. Brain Res Mol Brain Res 2000;79:102-9. https://doi.org/10.1016/S0169-328X(00)00105-4
  25. Asamoto S, Takeshige C. Activation of the satiety center by auricular acupuncture point stimulation. Brain Res Bull 1992;29:157-64. https://doi.org/10.1016/0361-9230(92)90021-O
  26. Zhao M, Liu Z, Su J. The time-effect relationship of central action in acupuncture treatment for weight reduction. J Tradit Chin Med 2000;20:26-9.