DOI QR코드

DOI QR Code

Effects of Coenzyme Q10 on the Expression of Genes involved in Lipid Metabolism in Laying Hens

Coenzyme Q10 첨가 급여가 산란계의 지방대사 연관 유전자 발현에 미치는 영향

  • Jang, In Surk (Department of Animal Science and Biotechnology, Gyeongnam National University of Science and Technology) ;
  • Moon, Yang Soo (Department of Animal Science and Biotechnology, Gyeongnam National University of Science and Technology)
  • 장인석 (경남과학기술대학교 동물생명과학과) ;
  • 문양수 (경남과학기술대학교 동물생명과학과)
  • Received : 2016.03.02
  • Accepted : 2016.03.09
  • Published : 2016.03.31

Abstract

The aim of this study was to investigate the expression patterns of key genes involved in lipid metabolism in response to dietary Coenzyme Q10 (CoQ10) in hens. A total of 36 forty week-old Lohmann Brown were randomly allocated into 3 groups consisting of 4 replicates of 3 birds. Laying hens were subjected to one of following treatments: Control (BD, basal diet), T1 (BD+ CoQ10 100 mg/kg diet) and T2 (BD+ micellar of CoQ10 100 mg/kg diet). Birds were fed ad libitum a basal diet or the basal diet supplemented with CoQ10 for 5 weeks. Total RNA was extracted from the liver for quantitative RT-PCR. The mRNA levels of HMG-CoA reductase(HMGCR) and sterol regulatory element-binding proteins(SREBP)2 were decreased more than 30~50% in the liver of birds fed a basal diet supplemented with CoQ10 (p<0.05). These findings suggest that dietary CoQ10 can reduce cholesterol levels by the suppression of the hepatic HMGCR and SREBP2 genes. The gene expressions of liver X receptor (LXR) and SREBP1 were down regulated due to the addition of CoQ10 to the feed (p<0.05). The homeostasis of cholesterol can be regulated by LXR and SREBP1 in cholesterol-low-conditions. The supplement of CoQ10 caused a decreased expression of lipid metabolism-related genes including $PPAR{\gamma}$, XBP1, FASN, and GLUTs in the liver of birds (p<0.05). These data suggest that CoQ10 might be used as a dietary supplement to reduce cholesterol levels and to regulate lipid homeostasis in laying hens.

Coenzyme Q10(CoQ10)은 자연계에 널리 분포하는 화합물로 세포호흡과 항산화제로서 그 기능이 잘 알려졌지만, 최근 유전자들의 발현 조절자로서의 가능성도 제시되었다. 따라서 본 연구는 산란계에서 CoQ10의 첨가 급이가 콜레스테롤과 지방산 대사관련 유전자들의 발현에 미치는 영향을 관찰하고자 실시하였다. Lohmann Brown(40주령) 36수를 CoQ10의 첨가원에 따라 대조군(CON, basal diet(BD)), CoQ10 건조분말 급여군(T1, BD+CoQ10 100 mg/kg 사료) 및 CoQ10 건조분말 유화처리군(T2, BD+micellar of CoQ10 100 mg/kg 사료) 등 모두 3처리구로 설정하여 5주간 사양시험을 실시하였다. 시험 종료 후 각 개체의 간으로부터 total RNA를 추출하고, real-time PCR을 이용하여 유전자들의 발현을 분석하였다. 콜레스테롤 합성 과정에서 주요 조절 효소인 HMGCoA reductase(HMGCR)의 유전자 발현은 대조구에 비하여 CoQ10 분말첨가인 T1과 유화처리된 T2 처리구에서 모두 약 50%씩 억제되었다(p<0.05). 내생 콜레스테롤의 합성을 촉진시키는 전사인자인 SREBP2 mRNA 발현 또한 대조구와 비교해서 T1과 T2에서 각각 30%와 40% 감소하였다(p<0.05). CoQ10의 첨가 급이는 대조구에 비하여 liver X receptor(LXR) 유전자가 약 30~35% 그 발현이 억제되었으며, sterol regulatory element-binding proteins(SREBPs)1 또한 T2에서 약 40% 유전자 발현이 감소하였다(P<0.05). 전사인자인 $PPAR{\gamma}$와 XBP1은 CoQ10에 의하여 약 15~40% 수준으로 효과적으로 억제됨을 확인하였다(p<0.05). 세포 내부로의 에너지 공급원인 포도당의 흡수를 담당하는 GLUT2는 약 35~60% 그리고 GLUT8은 약 25~30%의 유전자발현 각각 감소함을 보였다(p<0.05). CoQ10의 섭취는 중성지방 합성을 위한 지방합성효소(FASN)의 유전자 발현을 분말처리군에서 약 30%, 유화처리군에서 약 65% 억제됨을 확인하였다(P<0.05). 본 연구결과는 CoQ10 첨가급여가 콜레스테롤 및 지방대사 관련 유전자 발현에 영향을 미치며, 세포내 콜레스테롤과 지방의 생성도 억제할 수 있음을 보여주었다.

Keywords

References

  1. Albano CB, Muralikrishnan D, Ebadi M 2002 Distribution of coenzyme Q homologues in brain. Neurochem Res 27(5): 359-368. https://doi.org/10.1023/A:1015591628503
  2. Battino M, Ferri E, Gorini A, Villa RF, Rodriguez Huertas JF, Fiorella P, Genova ML, Lenaz G, Marchetti M 1990 Natural distribution and occurrence of coenzyme Q homologues. Membr Biochem 9(3):179-190. https://doi.org/10.3109/09687689009025839
  3. Beyer RE 1992 An analysis of the role of coenzyme Q in free radical generation and as an antioxidant. Biochem Cell Biol 70(6):390-403. https://doi.org/10.1139/o92-061
  4. Bhagavan HN, Chopra RK 2006 Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res 40(5):445-453. https://doi.org/10.1080/10715760600617843
  5. Carver FM, Shibley IA Jr, Pennington JS, Pennington SN 2001 Differential expression of glucose transporters during chick embryogenesis. Cell Mol Life Sci 58(4):645-652. https://doi.org/10.1007/PL00000887
  6. Cook F, Briggs GM 1977 Egg Science and Technology, second ed., eds. Stadelman WJ and Cotterill OJ, Avi Publishing Company, Westport, pp. 92-108.
  7. Elkin RG, Zhong Y, Donkin SS, Hengstschlager-Ottnad E, Schneider WJ 2006 Effects of atorvastatin on lipid metabolism in normolipidemic and hereditary hyperlipidemic, non-laying hens. Comp Biochem Physiol B Biochem Mol Biol 143(3):319-329. https://doi.org/10.1016/j.cbpb.2005.12.002
  8. Foufelle F, Ferre P 2002 New perspectives in the regulation of hepatic glycolytic and lipogenic genes by insulin and glucose: A role for the transcription factor sterol regulatory element binding protein-1c. Biochem J 366:377-391. https://doi.org/10.1042/bj20020430
  9. Geng AL, Guo YM 2005 Effects of dietary coenzyme Q10 supplementation on hepatic mitochondrial function and the activities of respiratory chain-related enzymes in ascitic broiler chickens. Br Poult Sci 46(5):626-634. https://doi.org/10.1080/00071660500273292
  10. Groneberg DA, Kindermann B, Althammer M, Klapper M, Vormann J, Littarru GP, Doring F 2005 Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells. Int J Biochem Cell Biol 37(6):1208-1218. https://doi.org/10.1016/j.biocel.2004.11.017
  11. Honda K, Kamisoyama H, Motoori T, Saneyasu T, Hasegawa S 2010 Effect of dietary coenzyme Q10 on cholesterol metabolism in growing chickens. J Poult Sci 47:41-47. https://doi.org/10.2141/jpsa.009063
  12. Honda K, Saneyasu T, Motoki T, Park Y, Kamisoyama H 2013 Dietary coenzyme Q10 suppressed hepatic hydroxymethylglutaryl-CoA reductase activity in laying hens. Biosci Biotechnol Biochem 77(7):1572-1574. https://doi.org/10.1271/bbb.130039
  13. Jang IS, Moon YS 2015 Effects of lycopene on the expression of lipid metabolism, glucose transport and pro-inflammatory related genes in chickens. Korean J Poult Sci 42:231-238. https://doi.org/10.5536/KJPS.2015.42.3.231
  14. Kalen A, Norling B, Appelkvist EL, Dallner G 1987 Ubiquinone biosynthesis by the microsomal fraction from rat liver. Biochim Biophys Acta 926(1):70-78. https://doi.org/10.1016/0304-4165(87)90183-8
  15. Kamisoyama H, Honda K, Kitaguchi K, Hasegawa S 2010 Transfer of dietary coenzyme Q10 into the egg yolk of laying hens. J Poult Sci 47:28-33. https://doi.org/10.2141/jpsa.009037
  16. Kono T, Nishida M, Nishiki Y, Seki Y, Sato K, Akiba Y 2005 Characterization of glucose transporter (GLUT) gene expression in broiler chickens. Br Poult Sci 46(4):510-515. https://doi.org/10.1080/00071660500181289
  17. Krishnaiah KV, Ramasarma T 1970 Regulation of hepatic cholesterolgenesis by ubiquinone. Biochim Biophys Acta 202(2):332-342. https://doi.org/10.1016/0005-2760(70)90195-5
  18. Lee AH, Scapa EF, Cohen DE, Glimcher LH 2008 Regulation of hepatic lipogenesis by the transcription factor XBP1. Science 320(5882):1492-1496. https://doi.org/10.1126/science.1158042
  19. Livak KJ, Schmittgen TD 2001 Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C(T)) method. Methods 25(4):402-408. https://doi.org/10.1006/meth.2001.1262
  20. Maxwell MH, Robertson GW 1998 UK survey of broiler ascites and sudden death syndromes in 1993. Br Poult Sci 39(2):203-215. https://doi.org/10.1080/00071669889132
  21. Modi K, Santani DD, Goyal RK, Bhatt PA 2006 Effect of coenzyme Q10 on catalase activity and other antioxidant parameters in streptozotocin-induced diabetic rats. Biol Trace Elem Res 109(1):25-34. https://doi.org/10.1385/BTER:109:1:025
  22. Nakamura Y, Okamura T, Tamaki S, Kadowaki T, Hayakawa T, Kita Y, Okayama A, Ueshima H 2004 Egg consumption, serum cholesterol, and cause-specific and all-cause mortality: The national integrated project for prospective observation of non-communicable disease and its trends in the aged, 1980 (NIPPON DATA80). Am J Clin Nutr 80: 58-63. https://doi.org/10.1093/ajcn/80.1.58
  23. O'Hea EK, Leveille GA 1968 Lipogenesis in isolated adipose tissue of the domestic chick (Gallus domesticus). Comp Biochem Physiol 26(1):111-120. https://doi.org/10.1016/0010-406X(68)90317-4
  24. SAS 1996 User's Guide: Statistics Version 6.12 Ed. SAS Inst., Inc., Cary, NC.
  25. Saneyasu T, Shiragaki M, Nakanishi K, Kamisoyama H, Honda K 2013 Effects of short term fasting on the expression of genes involved in lipid metabolism in chicks. Comp Biochem Physiol B Biochem Mol Biol 165(2):114-118. https://doi.org/10.1016/j.cbpb.2013.03.005
  26. Sato K, Kamada T 2011 Regulation of bile acid, cholesterol, and fatty acid synthesis in chicken primary hepatocytes by different concentrations of T0901317, an agonist of liver X receptors. Comp Biochem Physiol A Mol Integr Physiol 158(2):201-206. https://doi.org/10.1016/j.cbpa.2010.10.028
  27. Schadinger SE, Bucher NL, Schreiber BM, Farmer SR 2005 PPARgamma2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes. Am J Physiol Endocrinol Metab 288(6):E1195-1205. https://doi.org/10.1152/ajpendo.00513.2004