The Relationship between Homocysteine, Obesity, Glucose and Lipid Profiles in Small-Breed Dogs

소형견종에서 Homocysteine과 비만, 당 관련 인자, 지방 관련인자의 상관관계에 대한 연구

  • Lee, Seung-Gon (Choong-Hyun Animal Medical Center) ;
  • Nam, Hyo-Seung (Section of Small Animal Internal Medicine, School of Veterinary Medicine and Institute of Veterinary Medicine, Kangwon National University) ;
  • Hyun, Chang-Baig (Section of Small Animal Internal Medicine, School of Veterinary Medicine and Institute of Veterinary Medicine, Kangwon National University)
  • Accepted : 2012.08.20
  • Published : 2012.08.30

Abstract

This study was conducted to evaluate whether plasma homocysteine levels were related to obesity or its contributing factors (e.g., lipids, insulin, glucose, glucagon, and fructosamine) in dogs without systemic diseases such as diabetes or renal failure. For achieving our study goal, 100 client-owned dogs without systemic diseases were enrolled in this study. Fasting glucose concentration; lipid profile (i.e., total triglycerides [TG], total cholesterol [TC], highdensity lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol [LDL-C]); and fructosamine, insulin, and glucagon levels were determined. The dogs were subdivided by the body condition score (BCS). The median levels of homocysteine were considerably higher in obese dogs than in lean and normal dogs. Interestingly, not only was homocysteine positively associated with the level of HDL-C, but also found to have a significant positive association with TG, TC, plasma glucagon levels, and fructosamine. In contrast, LDL-C, fasting glucose and insulin did not show any association with homocysteine. The findings presented, suggest that elevated levels of homocysteine may play a biological role in obesity in dogs.

본 연구는 건강한 개에서 혈장 homocysteine농도가 비만이나 비만 관련인자(예, 지방, 인슐린, 혈당, 글루카곤, fructosamine)들과 어떤 상관관계가 있는지를 확인하기 위해 실시되었다. 이를 위해, 절식시 혈당, 지방지수(예, total triglycerides [TG], total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C]과 low-density lipoprotein cholesterol [LDL-C]), fructosamine, insulin 및 glucagon 농도를 각각 측정하였다. 실험에 사용된 개들은 body condition score (BCS)에 따라 분류하였다. 평균 혈장 homocysteine 농도는 비만한 개 집단이 정상이나 마른 개 집단에 비해 상당히 높았다. 또한 혈장 homocysteine농도는 HDL-C농도 뿐아니라 TG, TC, 혈장 glucagon 및 fructosamine 농도와도 밀접한 상관관계를 가지고 있었다. 반대로 LDL-C 농도, 절식시 혈당농도 및 insulin농도는 아무런 상관관계가 확인되지 않았다. 본 연구 결과, homocysteine의 농도 상승이 비만견에서 생물학적으로 중요한 역할을 하는 것으로 추정된다.

Keywords

References

  1. Bailhache E, Nguyen P, Krempf M, Siliart B, Magot T, Ouguerram K. Lipoproteins abnormalities in obese insulinresistant dogs. Metabolism 2003; 52: 559-564. https://doi.org/10.1053/meta.2003.50110
  2. Barazzoni R, Zanetti M, Tiengo A, Tessari P. Protein metabolism in glucagonoma. Diabetologia 1999; 42: 326-329. https://doi.org/10.1007/s001250051158
  3. Barth RJ. Insulin resistance, obesity and the metabolic syndrome. S D Med 2011; Spec No: 22-27.
  4. Bjorck J, Hellgren M, Rastam L, Lindblad U. Associations between serum insulin and homocysteine in a Swedish population-a potential link between the metabolic syndrome and hyperhomocysteinemia: the Skaraborg project. Metabolism 2006; 55: 1007-1013. https://doi.org/10.1016/j.metabol.2006.03.010
  5. Budak N, Yazici C, Ozturk A, Bayram F, Mazicio lu MM, Kurtoglu S. Is plasma homocysteine level associated with metabolic syndrome components in adolescents? Metab Syndr Relat Disord 2009; 7: 357-362. https://doi.org/10.1089/met.2008.0037
  6. Chandler ML, Payne-James JJ. Prospective evaluation of a peripherally administered three-in-one parenteral nutrition product in dogs. J Small Anim Pract 2006; 47: 518-523. https://doi.org/10.1111/j.1748-5827.2006.00173.x
  7. Davison LJ, Podd SL, Ristic JM, Herrtage ME, Parnham A, Catchpole B. Evaluation of two point-of-care analysers for measurement of fructosamine or haemoglobin A1c in dogs. J Small Anim Pract 2002; 43: 526-532. https://doi.org/10.1111/j.1748-5827.2002.tb00025.x
  8. Delpierre G, Collard F, Fortpied J, Van Schaftingen E. Fructosamine 3-kinase is involved in an intracellular deglycation pathway in human erythrocytes. Biochem J 2002; 365: 801-
  9. Ercan M, Konukoglu D. Role of plasma viscosity and plasma homocysteine level on hyperinsulinemic obese female subjects. Clin Hemorheol Microcirc 2008; 38: 227-234.
  10. Finch JM, Joseph J. Homocysteine, cardiovascular inflammation, and myocardial remodeling. Cardiovasc Hematol Disord Drug Targets 2010; 10: 241-245. https://doi.org/10.2174/187152910793743887
  11. Fonseca VA, Fink LM, Kern PA. Insulin sensitivity and plasma homocysteine concentrations in non-diabetic obese and normal weight subjects. Atherosclerosis 2003; 167: 105-109. https://doi.org/10.1016/S0021-9150(02)00386-6
  12. Fruchart JC, Nierman MC, Stroes ES, Kastelein JJ, Duriez P. New risk factors for atherosclerosis and patient risk assessment. Circulation 2004; 109 (Suppl): III15-III 19.
  13. Guyard-Dangremont V, Desrumaux C, Gambert P, Lallemant C, Lagrost L. Phospholipid and cholesteryl ester transfer activities in plasma from 14 vertebrate species. Relation to atherogenesis susceptibility. Comp Biochem Physiol B Biochem Mol Biol 1998; 120: 517-525. https://doi.org/10.1016/S0305-0491(98)10038-X
  14. Hess RS. Insulin resistance in dogs. Vet Clin North Am Small Anim Pract 2010; 40: 309-316. https://doi.org/10.1016/j.cvsm.2009.12.001
  15. Herrmann M, Taban-Shomal O, Hübner U, Böhm M, Herrmann W. A review of homocysteine and heart failure. Eur J Heart Fail 2006; 8: 571-576. https://doi.org/10.1016/j.ejheart.2005.11.016
  16. Herrmann W. The importance of hyperhomocysteinemia as a risk factor for diseases: an overview. Clin Chem Lab Med 2001; 39: 666-674.
  17. Hofmann MA, Kohl B, Zumbach MS, Borcea V, Bierhaus A, Henkels M, Amiral J, Schmidt AM, Fiehn W, Ziegler R, Wahl P, Nawroth PP. Hyperhomocyst(e)inemia and endothelial dysfunction in IDDM. Diabetes Care 1998; 21: 841-848. https://doi.org/10.2337/diacare.21.5.841
  18. Jacobs RL, Stead LM, Brosnan ME, Brosnan JT. Hyperglucagonemia in rats results in decreased plasma homocysteine and increased flux through the transsulfuration pathway in liver. J Biol Chem 2001; 276: 43740-43747. https://doi.org/10.1074/jbc.M107553200
  19. Karatela RA, Sainani GS. Plasma homocysteine in obese, overweight and normal weight hypertensives and normotensives. Indian Heart J 2009; 61: 156-159.
  20. Liao D, Tan H, Hui R, Li Z, Jiang X, Gaubatz J, Yang F, Durante W, Chan L, Schafer AI, Pownall HJ, Yang X, Wang H. Hyperhomocysteinemia decreases circulating high-density lipoprotein by inhibiting apolipoprotein A-I Protein synthesis and enhancing HDL cholesterol clearance. Circ Res 2006; 99: 598-606. https://doi.org/10.1161/01.RES.0000242559.42077.22
  21. Maldonado EN, Romero JR, Ochoa B, Aveldano MI. Lipid and fatty acid composition of canine lipoproteins. Comp Biochem Physiol B Biochem Mol Biol 2001; 128: 719-729. https://doi.org/10.1016/S1096-4959(00)00366-3
  22. Mikael LG, Wang XL, Wu Q, Jiang H, Maclean KN, Rozen R. Hyperhomocysteinemia is associated with hypertriglyceridemia in mice with methylenetetrahydrofolate reductase deficiency. Mol Genet Metab 2009; 98: 187-194. https://doi.org/10.1016/j.ymgme.2009.05.011
  23. Meigs JB, Jacques PF, Selhub J, Singer DE, Nathan DM, Rifai N, D'Agostino RB Sr, Wilson PW. Fasting plasma homocysteine levels in the insulin resistance syndrome: the Framingham offspring study. Diabetes Care 2001; 24: 1403-1410. https://doi.org/10.2337/diacare.24.8.1403
  24. Mawby DI, Bartges JW, d'Avignon A, Laflamme DP, Moyers TD, Cottrell T. Comparison of various methods for estimating body fat in dogs. J Am Anim Hosp Assoc 2004; 40: 109-114.
  25. Mazza A, Bossone E, Mazza F, Distante A. Reduced serum homocysteine levels in type 2 diabetes. Nutr Metab Cardiovasc Dis 2005; 15: 118-124. https://doi.org/10.1016/j.numecd.2004.03.001
  26. McMichael MA, Freeman LM, Selhub J, Rozanski EA, Brown DJ, Nadeau MR, Rush JE. Plasma homocysteine, B vitamins, and amino acid concentrations in cats with cardiomyopathy and arterial thromboembolism. J Vet Intern Med 2000; 14: 507-512. https://doi.org/10.1111/j.1939-1676.2000.tb02268.x
  27. Obeid R, Herrmann W. Homocysteine and lipids: S-adenosyl methionine as a key intermediate. FEBS Lett 2009; 583: 1215-1225. https://doi.org/10.1016/j.febslet.2009.03.038
  28. Pinkney JH, Stehouwer CD, Coppack SW, Yudkin JS. Endothelial dysfunction: cause of the insulin resistance syndrome. Diabetes 1997; 46 (Suppl 2): S9-S13.
  29. Puavilai W, Laorugpongse D, Deerochanawong C, Muthapongthavorn N, Srilert P. The accuracy in using modified Friedewald equation to calculate LDL from non-fast triglyceride: a pilot study. J Med Assoc Thai 2009; 92: 182-187.
  30. Reimers TJ, Cowan RG, McCann JP, Ross MW. Validation of a rapid solid-phase radioimmunoassay for canine, bovine, and equine insulin. Am J Vet Res 1982; 43: 1274-1278.
  31. Robillon JF, Canivet B, Candito M, Sadoul JL, Jullien D, Morand P, Chambon P, Freychet P. Type 1 diabetes mellitus and homocyst(e)ine. Diabete Metab 1994; 20: 494-496.
  32. Rossi S, Rossi G, Giordano A, Paltrinieri S. Homocysteine measurement by an enzymatic method and potential role of homocysteine as a biomarker in dogs. J Vet Diagn Invest 2008; 20: 644-649. https://doi.org/10.1177/104063870802000520
  33. Schalinske KL. Interrelationship between diabetes and homocysteine metabolism: hormonal regulation of cystathionine beta-synthase. Nutr Rev 2003; 61: 136-138. https://doi.org/10.1301/nr.2003.apr.136-138
  34. Son HR, d'Avignon DA, Laflamme DP. Comparison of dualenergy x-ray absorptiometry and measurement of total body water content by deuterium oxide dilution for estimating body composition in dogs. Am J Vet Res 1998; 59: 529-532.
  35. Suematsu N, Ojaimi C, Kinugawa S, Wang Z, Xu X, Koller A, Recchia FA, Hintze TH. Hyperhomocysteinemia alters cardiac substrate metabolism by impairing nitric oxide bioavailability through oxidative stress. Circulation 2007; 115: 255-262
  36. Uysal O, Arikan E, Cakir B. Plasma total homocysteine level and its association with carotid intima-media thickness in obesity. J Endocrinol Invest 2005; 28: 928-934.
  37. Veiga AP, Price CA, de Oliveira ST, Dos Santos AP, Campos R, Barbosa PR, González FH. Association of canine obesity with reduced serum levels of C-reactive protein. J Vet Diagn Invest 2008; 20: 224-228. https://doi.org/10.1177/104063870802000214
  38. Velez-Carrasco W, Merkel M, Twiss CO, Smith JD. Dietary methionine effects on plasma homocysteine and HDL metabolism in mice. J Nutr Biochem 2008; 19: 362-370. https://doi.org/10.1016/j.jnutbio.2007.05.005
  39. Vizzardi E, Bonadei I, Zanini G, Fiorina C, Raddino R, Dei Cas L. [Homocysteine: a casual link with heart failure?]. Minerva Med 2009; 100: 421-427.
  40. Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med 1998; 338: 1042-1050. https://doi.org/10.1056/NEJM199804093381507
  41. Wilt TJ, Rubins HB, Robins SJ, Riley WA, Collins D, Elam M, Rutan G, Anderson JW. Carotid atherosclerosis in men with low levels of HDL cholesterol. Stroke 1997; 28: 1919-1925. https://doi.org/10.1161/01.STR.28.10.1919
  42. Wollesen F, Brattstrom L, Refsum H, Ueland PM, Berglund L, Berne C. Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus. Kidney Int 1999; 55: 1028-1035. https://doi.org/10.1046/j.1523-1755.1999.0550031028.x