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Endothelial dysfunction in high fructose containing diet fed rats: Increased nitric oxide and decreased endothelin-1 levels in liver tissue

Year 2010, Volume: 37 Issue: 3, 193 - 198, 01.09.2010

Abstract

Objectives: Dietary high fructose consumption which is closely associated with endothelial dysfunction via insülin resistance has recently increased in developed countries.Insulin resistance has a promoter effect on many meta-bolic disorders such as syndrome X, polycystic ovary syn-drome, Type 2 diabetes mellitus etc. Our aim in this study is to understand the impact of increased fructose intake on metabolisms of glucose, insulin and endothelial dys-function by measuring nitric oxide (NO) and endothelin-1(ET-1) levels in hepatic tissue which is crucial in fructose metabolism. Materials and Methods: We designed an animal study to understand increased fructose intake on hepatic en-dothelium. Twenty adult male albino rats were divided into two groups; the study group (group 1, n=10) received isocaloric fructose enriched diet (fructose-fed rats, con-taining 18.3% protein, 60.3% fructose and 5.2% fat) while the control group received purifi ed regular chow (group 2,n=10) for 2 weeks. After feeding period, blood and hepatictissue samples were collected and glucose, insulin, NO and ET-1 levels were analysed. Results: We found increased fasting glucose and insülin levels and impaired glucose tolerance in fructose fed rats. Higher NO and lower ET–1 levels were also detected in hepatic tissue samples of the group 1. Conclusion: Increased fructose consumption has delete- rious effects on glucose tolerance, insulin resistance and may cause to endothelial dysfunction. Key words: Fructose consumption, endothelial dysfunc-tion, nitric oxide, endothelin-1, liver.

References

  • Bray GA, Nielsen SJ, Popkin BM. Consumption of high- fructose corn syrup in beverages may play a role in the epi- demic of obesity. Am J Clin Nutr 2004;79:537-43.
  • Vos MB, Kimmons JE, Gillespie C, Welsh J, Blanck HM. Di- etary fructose consumption among US children and adults: the Third National Health and Nutrition Examination Sur- vey. Medscape J Med 2008;10:160-5.
  • Shapiro A, Mu W, Roncal CA, Cheng KY, Johnson RJ, Scar- pace PJ. Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high fat feeding. Am J Physiol Regul Integr Comp Physiol 2008;295:R1365-9.
  • Lê KA, Tappy L. Metabolic effects of fructose. Curr Opin Clin Nutr Metab Care 2006;9:469-75.
  • Stanhope KL, Havel PJ. Fructose consumption: potential mechanisms for its effects to increase visceral adiposity and induce dyslipidemia and insulin resistance. Curr Opin Lipidol 2008;19:16–24.
  • Chisholm DJ, Campbell LV, Kraegen EW. Pathogenesis of the insulin resistance syndrome (syndrome X). Clin Exp Pharmacol Physiol 1997;24:782–4.
  • Oudot A, Behr-Roussel D, Compagnie S et al. Endothelial dysfunction in insulin-resistant rats is associated with oxi- dative stress and COX pathway dysregulation. Physiol Res 2009;58:499-509.
  • Feletou M, Vanhoutte VM. Endothelial dysfunction: a multifaceted disorder. Am J Physiol Heart Circ Physiol 2006;291:985-1002.
  • Pryor WA, Squadrito GL. The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol 1995;268:699-722.
  • Kelly GS. Insulin resistance: lifestyle and nutritional inter- ventions. Altern Med Rev 2000;5.109-32.
  • Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 1994;94:1172-9.
  • Rayssiguier Y, Gueux E, Nowacki W, Rock E, Mazur A. High fructose consumption combined with low dietary magnesium intake may increase the incidence of the meta- bolic syndrome by inducing infl ammation. Magnes Res 2006;19:237-43.
  • Basciano H, Federico L, Adeli K. Fructose, insulin resis- tance, and metabolic dyslipidemia. Nutr Metab 2005;2:5- 10.
  • Gaby AR. Adverse effects of dietary fructose. Altern Med Rev 2005;10:294-306.
  • Mayes PA: Intermediary metabolism of fructose. Am J Clin Nutr 1993;58:754-65.
  • Catena C, Giacchetti G, Novello M, Colussi G, Cavarape A, Sechi LA. Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension. Am J Hypertens 2003;16.973-8.
  • Porikos KP, van Itallie TB. Transient elevations of serum transaminase in healthy males on a high sucrose diet. Am J Clin Nutr 1979;32:959-63.
  • Oberhaensli RD, Galloway GJ. Taylor DJ, Bore PJ, Radda GK. Assessment of human liver metabolism by phospho- rus–31 magnetic resonance spectroscopy. Br J Radiol 1986;59:695-9.
  • Delbosc S, Paizanis E, Magous R, et al. Involvement of oxidative stress and NADPH oxidase activation in the development of cardiovascular complications in a model of insulin resistance, the fructose-fed rat. Atherosclerosis 2005;179:43-9
  • Busserolles J, Zimowska W, Rock E, Rayssiguier Y, Ma- zur A. Rats fed a high sucrose diet have altered heart an- tioxidant enzyme activity and gene expression. Life Sci 2002;71:1303–12.
  • Faure P, Rossini E, Lafond JL, Richard MJ, Favier A, Hal- imi S. Vitamin E improves the free radical defense system potential and insulin sensitivity of rats fed high fructose di- ets. J Nutr 1997;127:103-7.
  • Cosenzi A, Bernobich E, Bonavita M, Gris F, Odoni G, Bellini G. Role of nitric oxide in the early renal changes induced by high fructose diet in rats. Kidney Blood Pres Res 2002;25:363-9.
  • Busserolles J, Mazur A, Gueux E, Rock E, Rayssiquier Y. Metabolic syndrome in the rat: females are protected against the pro-oxidant effect of a high sucrose diet. Exp Biol Med 2002;227:837-42.
  • Lee DH, Lee JU, Kang DG, Paek YW, Chung DJ, Chung MY. Increased vascular endothelin–1 gene expression with unaltered nitric oxide synthase levels in fructose-induced hypertensive rats. Metabolism 2001;50:74-8.
  • Zhao CX, Xu X, Cui Y et al. Increased endothelial nitric oxide synthase expression reduces hypertension and hyper- insulinemia in fructose-treated rats. J Pharmacol Exp Ther 2009;328:610-20.

Yüksek fruktoz içeren diyetle beslenen ratlarda endotel disfonksiyonu: Karaciğerdokusunda artmıs nitrik oksit ve azalmıs endotelin-1 düzeyleri

Year 2010, Volume: 37 Issue: 3, 193 - 198, 01.09.2010

Abstract

Amaç: Gelismis ulkelerdeki diyetlerde fruktozun tüketilme sıklığı son yıllarda giderek artmaktadır. Artan fruktoz tuke-timi insulin rezistansı olusturarak endotel disfonksiyonuna yol acabilir. İnsulin rezistansı, sendrom X, polikistik over sendromu, tip 2 diabet gibi bircok metabolik bozukluğun patogenezinde altta yatan etkendir. Calısmamızın amacı, artmıs fruktoz tuketiminin, glukoz, insulin duzeylerine ve ayrıca metabolizmada kritik oneme sahip olan karaciğer dokusundaki endotel fonksiyonlarına olan etkilerini, nitrik oksit (NO) ve endothelin–1 (ET–1) olcerek değerlendir-mektir. Gereç ve yöntem: Calısmamızda 20 erkek sıcan iki gruba ayrıldı. Calısma grubu (grup 1, n=10) fruktozdan zenginlestirilmis izokalorik diyet ile (iceriği: %18.3 protein, %60.3 fruktoz ve %5.2 yağ), kontrol grubu ise (grup 2, n=10) purifi ye normal besin ile 2 hafta suresince beslendi. Beslenme periyodu sonrası kan ve hepatik doku ornekle-ri alınarak glukoz, insulin, NO ve ET–1 duzeyleri analiz edildi. Bulgular: Fruktozdan zengin beslenen sıcanlarda artmış aclık glukozu, insulin duzeyleri ve bozulmus glukoz tole-ransı izlendi. Grup 1 karaciğer dokularında ise yuksek NO ve dusuk ET–1 duzeyleri saptandı. Sonuç: Artmıs fruktoz tuketimi glukoz toleransını boz-makta ve insulin rezistansı olusturmaktadır. İnsulin rezis-tansı karaciğer dokusunda endotel disfonksiyonuna yol acabilir.

References

  • Bray GA, Nielsen SJ, Popkin BM. Consumption of high- fructose corn syrup in beverages may play a role in the epi- demic of obesity. Am J Clin Nutr 2004;79:537-43.
  • Vos MB, Kimmons JE, Gillespie C, Welsh J, Blanck HM. Di- etary fructose consumption among US children and adults: the Third National Health and Nutrition Examination Sur- vey. Medscape J Med 2008;10:160-5.
  • Shapiro A, Mu W, Roncal CA, Cheng KY, Johnson RJ, Scar- pace PJ. Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high fat feeding. Am J Physiol Regul Integr Comp Physiol 2008;295:R1365-9.
  • Lê KA, Tappy L. Metabolic effects of fructose. Curr Opin Clin Nutr Metab Care 2006;9:469-75.
  • Stanhope KL, Havel PJ. Fructose consumption: potential mechanisms for its effects to increase visceral adiposity and induce dyslipidemia and insulin resistance. Curr Opin Lipidol 2008;19:16–24.
  • Chisholm DJ, Campbell LV, Kraegen EW. Pathogenesis of the insulin resistance syndrome (syndrome X). Clin Exp Pharmacol Physiol 1997;24:782–4.
  • Oudot A, Behr-Roussel D, Compagnie S et al. Endothelial dysfunction in insulin-resistant rats is associated with oxi- dative stress and COX pathway dysregulation. Physiol Res 2009;58:499-509.
  • Feletou M, Vanhoutte VM. Endothelial dysfunction: a multifaceted disorder. Am J Physiol Heart Circ Physiol 2006;291:985-1002.
  • Pryor WA, Squadrito GL. The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol 1995;268:699-722.
  • Kelly GS. Insulin resistance: lifestyle and nutritional inter- ventions. Altern Med Rev 2000;5.109-32.
  • Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 1994;94:1172-9.
  • Rayssiguier Y, Gueux E, Nowacki W, Rock E, Mazur A. High fructose consumption combined with low dietary magnesium intake may increase the incidence of the meta- bolic syndrome by inducing infl ammation. Magnes Res 2006;19:237-43.
  • Basciano H, Federico L, Adeli K. Fructose, insulin resis- tance, and metabolic dyslipidemia. Nutr Metab 2005;2:5- 10.
  • Gaby AR. Adverse effects of dietary fructose. Altern Med Rev 2005;10:294-306.
  • Mayes PA: Intermediary metabolism of fructose. Am J Clin Nutr 1993;58:754-65.
  • Catena C, Giacchetti G, Novello M, Colussi G, Cavarape A, Sechi LA. Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension. Am J Hypertens 2003;16.973-8.
  • Porikos KP, van Itallie TB. Transient elevations of serum transaminase in healthy males on a high sucrose diet. Am J Clin Nutr 1979;32:959-63.
  • Oberhaensli RD, Galloway GJ. Taylor DJ, Bore PJ, Radda GK. Assessment of human liver metabolism by phospho- rus–31 magnetic resonance spectroscopy. Br J Radiol 1986;59:695-9.
  • Delbosc S, Paizanis E, Magous R, et al. Involvement of oxidative stress and NADPH oxidase activation in the development of cardiovascular complications in a model of insulin resistance, the fructose-fed rat. Atherosclerosis 2005;179:43-9
  • Busserolles J, Zimowska W, Rock E, Rayssiguier Y, Ma- zur A. Rats fed a high sucrose diet have altered heart an- tioxidant enzyme activity and gene expression. Life Sci 2002;71:1303–12.
  • Faure P, Rossini E, Lafond JL, Richard MJ, Favier A, Hal- imi S. Vitamin E improves the free radical defense system potential and insulin sensitivity of rats fed high fructose di- ets. J Nutr 1997;127:103-7.
  • Cosenzi A, Bernobich E, Bonavita M, Gris F, Odoni G, Bellini G. Role of nitric oxide in the early renal changes induced by high fructose diet in rats. Kidney Blood Pres Res 2002;25:363-9.
  • Busserolles J, Mazur A, Gueux E, Rock E, Rayssiquier Y. Metabolic syndrome in the rat: females are protected against the pro-oxidant effect of a high sucrose diet. Exp Biol Med 2002;227:837-42.
  • Lee DH, Lee JU, Kang DG, Paek YW, Chung DJ, Chung MY. Increased vascular endothelin–1 gene expression with unaltered nitric oxide synthase levels in fructose-induced hypertensive rats. Metabolism 2001;50:74-8.
  • Zhao CX, Xu X, Cui Y et al. Increased endothelial nitric oxide synthase expression reduces hypertension and hyper- insulinemia in fructose-treated rats. J Pharmacol Exp Ther 2009;328:610-20.
There are 25 citations in total.

Details

Primary Language Turkish
Journal Section Research Articles
Authors

Mustafa Altas This is me

Ahmet Var This is me

Can Köse This is me

Kemal Özbilgin This is me

Zeki Arı This is me

Publication Date September 1, 2010
Submission Date March 2, 2015
Published in Issue Year 2010 Volume: 37 Issue: 3

Cite

APA Altas, M., Var, A., Köse, C., Özbilgin, K., et al. (2010). Yüksek fruktoz içeren diyetle beslenen ratlarda endotel disfonksiyonu: Karaciğerdokusunda artmıs nitrik oksit ve azalmıs endotelin-1 düzeyleri. Dicle Tıp Dergisi, 37(3), 193-198.
AMA Altas M, Var A, Köse C, Özbilgin K, Arı Z. Yüksek fruktoz içeren diyetle beslenen ratlarda endotel disfonksiyonu: Karaciğerdokusunda artmıs nitrik oksit ve azalmıs endotelin-1 düzeyleri. diclemedj. September 2010;37(3):193-198.
Chicago Altas, Mustafa, Ahmet Var, Can Köse, Kemal Özbilgin, and Zeki Arı. “Yüksek Fruktoz içeren Diyetle Beslenen Ratlarda Endotel Disfonksiyonu: Karaciğerdokusunda artmıs Nitrik Oksit Ve azalmıs Endotelin-1 düzeyleri”. Dicle Tıp Dergisi 37, no. 3 (September 2010): 193-98.
EndNote Altas M, Var A, Köse C, Özbilgin K, Arı Z (September 1, 2010) Yüksek fruktoz içeren diyetle beslenen ratlarda endotel disfonksiyonu: Karaciğerdokusunda artmıs nitrik oksit ve azalmıs endotelin-1 düzeyleri. Dicle Tıp Dergisi 37 3 193–198.
IEEE M. Altas, A. Var, C. Köse, K. Özbilgin, and Z. Arı, “Yüksek fruktoz içeren diyetle beslenen ratlarda endotel disfonksiyonu: Karaciğerdokusunda artmıs nitrik oksit ve azalmıs endotelin-1 düzeyleri”, diclemedj, vol. 37, no. 3, pp. 193–198, 2010.
ISNAD Altas, Mustafa et al. “Yüksek Fruktoz içeren Diyetle Beslenen Ratlarda Endotel Disfonksiyonu: Karaciğerdokusunda artmıs Nitrik Oksit Ve azalmıs Endotelin-1 düzeyleri”. Dicle Tıp Dergisi 37/3 (September 2010), 193-198.
JAMA Altas M, Var A, Köse C, Özbilgin K, Arı Z. Yüksek fruktoz içeren diyetle beslenen ratlarda endotel disfonksiyonu: Karaciğerdokusunda artmıs nitrik oksit ve azalmıs endotelin-1 düzeyleri. diclemedj. 2010;37:193–198.
MLA Altas, Mustafa et al. “Yüksek Fruktoz içeren Diyetle Beslenen Ratlarda Endotel Disfonksiyonu: Karaciğerdokusunda artmıs Nitrik Oksit Ve azalmıs Endotelin-1 düzeyleri”. Dicle Tıp Dergisi, vol. 37, no. 3, 2010, pp. 193-8.
Vancouver Altas M, Var A, Köse C, Özbilgin K, Arı Z. Yüksek fruktoz içeren diyetle beslenen ratlarda endotel disfonksiyonu: Karaciğerdokusunda artmıs nitrik oksit ve azalmıs endotelin-1 düzeyleri. diclemedj. 2010;37(3):193-8.