Journal of Nutrition and Health

  • 제51권6호
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  • Pages.489-497
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  • 2018
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  • 2288-3886(pISSN)
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  • 2288-3959(eISSN)
한국영양학회 (The Korean Nutrition Society)
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고지방식이로 유도한 비만이 마우스의 조직 아연 농도와 아연수송체 발현에 미치는 영향

Effects of high-fat diet induced obesity on tissue zinc concentrations and zinc transporter expressions in mice

  • 민별초롱 (경희대학교 생활과학대학 식품영양학과) ;
  • 정자용 (경희대학교 생활과학대학 식품영양학과)
  • Min, Byulchorong (Department of Food & Nutrition, College of Human Ecology, Kyung Hee University) ;
  • Chung, Jayong (Department of Food & Nutrition, College of Human Ecology, Kyung Hee University)
  • 투고 : 2018.10.29
  • 심사 : 2018.11.16
  • 발행 : 2018.12.31
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초록

본 연구에서는 고지방식이로 유도한 비만군과 저지방식이를 공급한 대조군에서 각 조직의 아연 농도와 아연수송체 발현 수준을 비교하여, 비만 상태가 아연 대사에 미치는 영향을 파악하고자 하였다. C57BL/6J mice를 두 군으로 나누어 각 군당 15마리씩 고지방식이 (비만군) 또는 저지방식이 (대조군)를 총 15주간 공급하였다. 본 연구 결과, 비만군은 대조군에 비해 체중 증가량, 부위별 지방조직, 혈청과 간의 중성지방과 콜레스테롤 농도, 혈청 ALT 및 AST 활성 등이 모두 유의적으로 높게 나타났다. 또한 혈청 렙틴과 염증성 사이토카인인 IL-6의 농도도 비만군에서 유의적으로 증가하였다. 조직 별 아연 농도를 비교한 결과, 간, 소장, 신장, 췌장 등의 측정한 모든 조직에서 비만군이 대조군에 비해 유의적으로 낮게 나타났으며, 대변으로 배설되는 아연 함량은 비만군이 대조군에 비해 유의적으로 높았다. 혈청 아연 농도의 경우 두 군 간 유의적인 차이가 없었으나, 혈청 내 아연-의존 금속효소인 ALP 활성은 비만군에서 대조군에 비해 유의적으로 낮게 나타나 아연의 기능적인 결핍을 확인하였다. 내인성 아연의 체외 배출에 관여하는 췌장 조직에서의 ZnT1 mRNA 수준은 비만군에서 대조군에 비해 유의적으로 높게 나타났으며, 식이 아연 흡수에 관여하는 소장에서의 Zip4와 ZnT1의 mRNA 수준은 두 군간에 유의적인 차이가 없었다. 간 조직의 경우, ZnT1과 Zip10 mRNA이 모두 비만군에서 유의적으로 증가하였다. 이상의 결과를 요약하면, 비만 상태는 아연의 배설 증가와 조직 내 아연 농도 감소를 유발하는 것으로 나타났으며, 이들 아연 대사의 변화는 췌장과 간 조직의 아연 수송체 발현 수준 변화와 밀접한 관련이 있는 것으로 보인다. 비만인들에서 아연 영양상태가 결핍되지 않도록 관심을 가져야 할 것으로 생각되며, 비만으로 인한 아연 대사의 이상 (dysfunction)을 억제하기 위해서는 아연 수송체 발현을 조절할 수 있는 요인들에 대한 이해가 더욱 필요할 것으로 생각된다.

Purpose: Obesity is often associated with disturbances in the mineral metabolism. The purpose of this study was to investigate the effects of high-fat diet-induced obesity on tissue zinc concentrations and zinc transporter expressions in mice. Methods: C57BL/6J male mice were fed either a control diet (10% energy from fat, control group) or a high-fat diet (45% energy from fat, obese group) for 15 weeks. The zinc concentrations in the serum, stool, and various tissues were measured by inductively coupled plasma (ICP)-atomic emission spectrophotometry or ICP-mass spectrophotometry. The levels of zinc transporter mRNAs in the liver, duodenum, and pancreas were measured by real-time RT-PCR. The levels of serum adipokines, such as leptin and IL-6, were determined. Results: The total body weight, adipose tissue weight, and hepatic TG and cholesterol concentrations were significantly higher in the obese group, as compared to the control group. The obese group had significantly higher levels of serum leptin and pro-inflammatory IL-6 concentrations, and had significantly lower levels of serum alkaline phosphatase activity. The zinc concentrations of the liver, kidney, duodenum, and pancreas were all significantly lower in the obese group than in the control group. On the other hand, the fecal zinc concentrations were significantly higher in the obese group than in the control group. The serum zinc concentrations were not significantly different between the two groups. The ZnT1 mRNA levels of the liver and the pancreas were significantly higher in the obese group, as compared to the control group. Hepatic Zip10 mRNA was also increased in the obese group. Conclusion: Our study findings suggest that obesity increases fecal zinc excretion and lowers the tissue zinc concentrations, which may be associated with alterations in the zinc transporter expressions.

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참고문헌

  1. Institute of Medicine; Food and Nutrition Board; Panel on Micronutrients; Subcommittees on Upper Reference Levels of Nutrients and of Interpretation and Use of Dietary Reference Intakes; Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, D.C.: National Academies Press; 2001.
  2. Solomons NW. Mild human zinc deficiency produces an imbalance between cell-mediated and humoral immunity. Nutr Rev 1998; 56(1 Pt 1): 27-28.
  3. Prasad AS. Zinc: an overview. Nutrition 1995; 11(1 Suppl): 93-99.
  4. Heyneman CA. Zinc deficiency and taste disorders. Ann Pharmacother 1996; 30(2): 186-187. https://doi.org/10.1177/106002809603000215
  5. Wessels I, Maywald M, Rink L. Zinc as a gatekeeper of immune function. Nutrients 2017; 9(12): E1286. https://doi.org/10.3390/nu9121286
  6. Hara T, Takeda TA, Takagishi T, Fukue K, Kambe T, Fukada T. Physiological roles of zinc transporters: molecular and genetic importance in zinc homeostasis. J Physiol Sci 2017; 67(2): 283-301. https://doi.org/10.1007/s12576-017-0521-4
  7. Hojyo S, Fukada T. Zinc transporters and signaling in physiology and pathogenesis. Arch Biochem Biophys 2016; 611: 43-50. https://doi.org/10.1016/j.abb.2016.06.020
  8. Lichten LA, Cousins RJ. Mammalian zinc transporters: nutritional and physiologic regulation. Annu Rev Nutr 2009; 29(1): 153-176. https://doi.org/10.1146/annurev-nutr-033009-083312
  9. Dufner-Beattie J, Wang F, Kuo YM, Gitschier J, Eide D, Andrews GK. The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc-regulated zinc transporter in mice. J Biol Chem 2003; 278(35): 33474-33481. https://doi.org/10.1074/jbc.M305000200
  10. Geiser J, De Lisle RC, Andrews GK. The zinc transporter Zip5 (Slc39a5) regulates intestinal zinc excretion and protects the pancreas against zinc toxicity. PLoS One 2013; 8(11): e82149. https://doi.org/10.1371/journal.pone.0082149
  11. Kaler P, Prasad R. Molecular cloning and functional characterization of novel zinc transporter rZip10 (Slc39a10) involved in zinc uptake across rat renal brush-border membrane. Am J Physiol Renal Physiol 2007; 292(1): F217-F229. https://doi.org/10.1152/ajprenal.00014.2006
  12. Cousins RJ, Liuzzi JP, Lichten LA. Mammalian zinc transport, trafficking, and signals. J Biol Chem 2006; 281(34): 24085-24089. https://doi.org/10.1074/jbc.R600011200
  13. Ennes Dourado Ferro F, de Sousa Lima VB, Mello Soares NR, Franciscato Cozzolino SM, do Nascimento Marreiro D. Biomarkers of metabolic syndrome and its relationship with the zinc nutritional status in obese women. Nutr Hosp 2011; 26(3): 650-654. https://doi.org/10.1590/S0212-16112011000300032
  14. Konukoglu D, Turhan MS, Ercan M, Serin O. Relationship between plasma leptin and zinc levels and the effect of insulin and oxidative stress on leptin levels in obese diabetic patients. J Nutr Biochem 2004; 15(12): 757-760. https://doi.org/10.1016/j.jnutbio.2004.07.007
  15. Marreiro DN, Fisberg M, Cozzolino SM. Zinc nutritional status and its relationships with hyperinsulinemia in obese children and adolescents. Biol Trace Elem Res 2004; 100(2): 137-149. https://doi.org/10.1385/BTER:100:2:137
  16. Voruganti VS, Cai G, Klohe DM, Jordan KC, Lane MA, Freeland-Graves JH. Short-term weight loss in overweight/obese low-income women improves plasma zinc and metabolic syndrome risk factors. J Trace Elem Med Biol 2010; 24(4): 271-276. https://doi.org/10.1016/j.jtemb.2010.05.001
  17. Ishikawa Y, Kudo H, Kagawa Y, Sakamoto S. Increased plasma levels of zinc in obese adult females on a weight-loss program based on a hypocaloric balanced diet. In Vivo 2005; 19(6): 1035-1037.
  18. Kennedy ML, Failla ML, Smith JC Jr. Influence of genetic obesity on tissue concentrations of zinc, copper, manganese and iron in mice. J Nutr 1986; 116(8): 1432-1441. https://doi.org/10.1093/jn/116.8.1432
  19. Chen MD, Lin PY. Zinc-induced hyperleptinemia relates to the amelioration of sucrose-induced obesity with zinc repletion. Obes Res 2000; 8(7): 525-529. https://doi.org/10.1038/oby.2000.65
  20. Francisco V, Pino J, Campos-Cabaleiro V, Ruiz-Fernandez C, Mera A, Gonzalez-Gay MA, Gomez R, Gualillo O. Obesity, fat mass and immune system: role for leptin. Front Physiol 2018; 9: 640. https://doi.org/10.3389/fphys.2018.00640
  21. La Cava A. Leptin in inflammation and autoimmunity. Cytokine 2017; 98: 51-58. https://doi.org/10.1016/j.cyto.2016.10.011
  22. Sanchez-Margalet V, Martín-Romero C, Santos-Alvarez J, Goberna R, Najib S, Gonzalez-Yanes C. Role of leptin as an immunomodulator of blood mononuclear cells: mechanisms of action. Clin Exp Immunol 2003; 133(1): 11-19. https://doi.org/10.1046/j.1365-2249.2003.02190.x
  23. Agrawal S, Gollapudi S, Su H, Gupta S. Leptin activates human B cells to secrete TNF-${\alpha}$, IL-6, and IL-10 via JAK2/STAT3 and p38MAPK/ERK1/2 signaling pathway. J Clin Immunol 2011; 31(3): 472-478. https://doi.org/10.1007/s10875-010-9507-1
  24. Zarrati M, Salehi E, Razmpoosh E, Shoormasti RS, Hosseinzadeh-Attar MJ, Shidfar F. Relationship between leptin concentration and body fat with peripheral blood mononuclear cells cytokines among obese and overweight adults. Ir J Med Sci 2017; 186(1): 133-142. https://doi.org/10.1007/s11845-016-1454-2
  25. Besecker BY, Exline MC, Hollyfield J, Phillips G, Disilvestro RA, Wewers MD, Knoell DL. A comparison of zinc metabolism, inflammation, and disease severity in critically ill infected and noninfected adults early after intensive care unit admission. Am J Clin Nutr 2011; 93(6): 1356-1364. https://doi.org/10.3945/ajcn.110.008417
  26. Alkhouri RH, Hashmi H, Baker RD, Gelfond D, Baker SS. Vitamin and mineral status in patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2013; 56(1): 89-92. https://doi.org/10.1097/MPG.0b013e31826a105d
  27. Griffin IJ, Kim SC, Hicks PD, Liang LK, Abrams SA. Zinc metabolism in adolescents with Crohn's disease. Pediatr Res 2004; 56(2): 235-239. https://doi.org/10.1203/01.PDR.0000132851.50841.D7
  28. Hennigar SR, Kelley AM, McClung JP. Metallothionein and zinc transporter expression in circulating human blood cells as biomarkers of zinc status: a systematic review. Adv Nutr 2016; 7(4): 735-746. https://doi.org/10.3945/an.116.012518
  29. Ray CS, Singh B, Jena I, Behera S, Ray S. Low alkaline phosphatase in adult population an indicator of zinc and magnesium deficiency. Curr Res Nutr Food Sci 2017; 5(3): 347-352. https://doi.org/10.12944/CRNFSJ.5.3.20
  30. Cho YE, Lomeda RA, Ryu SH, Sohn HY, Shin HI, Beattie JH, Kwun IS. Zinc deficiency negatively affects alkaline phosphatase and the concentration of Ca, Mg and P in rats. Nutr Res Pract 2007; 1(2): 113-119. https://doi.org/10.4162/nrp.2007.1.2.113
  31. Krebs NF. Overview of zinc absorption and excretion in the human gastrointestinal tract. J Nutr 2000; 130(5S Suppl): 1374S-1377S. https://doi.org/10.1093/jn/130.5.1374S
  32. King JC, Shames DM, Woodhouse LR. Zinc homeostasis in humans. J Nutr 2000; 130(5S Suppl): 1360S-1366S. https://doi.org/10.1093/jn/130.5.1360S
  33. Jackson MJ, Jones DA, Edwards RH, Swainbank IG, Coleman ML. Zinc homeostasis in man: studies using a new stable isotope-dilution technique. Br J Nutr 1984; 51(2): 199-208. https://doi.org/10.1079/BJN19840024
  34. Tamaki M, Fujitani Y, Hara A, Uchida T, Tamura Y, Takeno K, Kawaguchi M, Watanabe T, Ogihara T, Fukunaka A, Shimizu T, Mita T, Kanazawa A, Imaizumi MO, Abe T, Kiyonari H, Hojyo S, Fukada T, Kawauchi T, Nagamatsu S, Hirano T, Kawamori R, Watada H. The diabetes-susceptible gene SLC30A8/ZnT8 regulates hepatic insulin clearance. J Clin Invest 2013; 123(10): 4513-4524. https://doi.org/10.1172/JCI68807
  35. Schmitt S, Kury S, Giraud M, Dreno B, Kharfi M, Bezieau S. An update on mutations of the SLC39A4 gene in acrodermatitis enteropathica. Hum Mutat 2009; 30(6): 926-933. https://doi.org/10.1002/humu.20988
  36. Lazarczyk M, Pons C, Mendoza JA, Cassonnet P, Jacob Y, Favre M. Regulation of cellular zinc balance as a potential mechanism of EVER-mediated protection against pathogenesis by cutaneous oncogenic human papillomaviruses. J Exp Med 2008; 205(1): 35-42. https://doi.org/10.1084/jem.20071311
  37. Lang C, Murgia C, Leong M, Tan LW, Perozzi G, Knight D, Ruffin R, Zalewski P. Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation. Am J Physiol Lung Cell Mol Physiol 2007; 292(2): L577-L584. https://doi.org/10.1152/ajplung.00280.2006
  38. Chi ZH, Wang X, Wang ZY, Gao HL, Dahlstrom A, Huang L. Zinc transporter 7 is located in the cis-Golgi apparatus of mouse choroid epithelial cells. Neuroreport 2006; 17(17): 1807-1811. https://doi.org/10.1097/01.wnr.0000239968.06438.c5
  39. Wong CP, Magnusson KR, Ho E. Increased inflammatory response in aged mice is associated with age-related zinc deficiency and zinc transporter dysregulation. J Nutr Biochem 2013; 24(1): 353-359. https://doi.org/10.1016/j.jnutbio.2012.07.005
  40. Galvez-Peralta M, Wang Z, Bao S, Knoell DL, Nebert DW. Tissue-Specific induction of mouse ZIP8 and ZIP14 divalent cation/bicarbonate symporters by, and cytokine response to, inflammatory signals. Int J Toxicol 2014; 33(3): 246-258. https://doi.org/10.1177/1091581814529310
  41. Miyai T, Hojyo S, Ikawa T, Kawamura M, Irié T, Ogura H, Hijikata A, Bin BH, Yasuda T, Kitamura H, Nakayama M, Ohara O, Yoshida H, Koseki H, Mishima K, Fukada T. Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development. Proc Natl Acad Sci USA 2014; 111(32): 11780-11785. https://doi.org/10.1073/pnas.1323549111
  42. Maxel T, Svendsen PF, Smidt K, Lauridsen JK, Brock B, Pedersen SB, Rungby J, Larsen A. Expression patterns and correlations with metabolic markers of zinc transporters ZIP14 and ZNT1 in obesity and polycystic ovary syndrome. Front Endocrinol (Lausanne) 2017; 8: 38.

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