Th e effect of omega-3 fatty acid supplementation on plasma orexin A, plasma fatty acids, and anthropometric measurements in patients with narcolepsy

Amaç: Bu çalışmada narkolepsili hastalarda omega-3 (n-3) yağ asit desteğinin plazma oreksin A, plazma yağ asitleri ve antropometrik ölçümlere etkisini saptamak amaçlanmıştır. Yöntem ve gereç: Çalışma, 21-55 yaş arası 31 erkek birey (17 narkolepsili ve 14 sağlıklı) üzerinde yapılmıştır. Gruplara iki ay süresince günlük 1,4 g n-3 yağ asidi desteği verilmiştir. Çalışma başlangıcında ve sonunda bireylerin antropometrik ölçümleri alınmış plazmada oreksin, yağ asitleri ve diğer biyokimyasal parametreler analiz edilmiştir. Bulgular: Çalışma sonunda, hasta grubun antropometrik ölçüm ve diğer vücut bileşim değerlerinde istatistiksel olarak önemli değişiklik yokken (P > 0,05), kontrol grubunun vücut ağırlığı, beden kitle indeksi, bel/kalça oranı, vücut yağ (kg, %) değerlerindeki artış istatistiksel açıdan önemli bulunmuştur (P < 0,05). Hastaların çalışma başı ve sonunda plazma oreksin A düzeylerinde hem grup içi hem de gruplar arasında fark gözlenmemiştir (P > 0,05). Yine hastaların plazma seratonin düzeyleri çalışma başına göre, sonunda azalmış, insülin düzeyleri ise yükselmiştir (P < 0,05). Bireylerin grup içinde plazma n-6/n-3 oranında çalışma sonunda azalma olmasına karşın istatistiksel açıdan önemli değildir (P > 0,05). Plazma n-6/n-3 oranında gruplar arasında ise istatistiksel farklılık görülmüştür (P < 0,05). Kontrol grubundaki bireylerin çalışma başında plazma oreksin A düzeyi ile plazma n-3 yağ asitleri arasında korelasyon görülmüştür (P < 0,05). Yine çalışmada n-3 suplemantasyonu ardından yağ asitlerinin artmasına bağlı olarak plazma oreksin A düzeyi ile bazı yağ asitleri arasında korelasyon gözlenmiştir (P < 0,05). Sonuç: Bu veriler; n-3 yağ asidi desteğinin plazma oreksin A düzeyini yükseltmediğini ancak diğer bazı biyokimyasal parametreleri etkilediğini göstermektedir.

Narkolepsili hastalarda omega-3 yağ asit desteğinin plazma oreksin A, plazma yağ asitleri ve antropometrik ölçümlere etkisi

Aim: To determine the eff ect of omega-3 (n-3) fatty acid supplementation on plasma orexin A, plasma fatty acids, and anthropometric measurements in patients with narcolepsy. Materials and methods: Th e study was performed on 17 males with narcolepsy and 14 healthy males between the ages of 21-55. An n-3 fatty acid supplement of 1.4 g/day was administered to the groups for 2 months. Th e anthropometric measurements of the individuals were taken at the onset and the end of trial, and orexin, fatty acids, and other biochemical parameters in the plasma were analyzed. Results: While there was no statistically signifi cant change in anthropometric measurements or the other body composition values of the patient group (P > 0.05), there was a statistically signifi cant increase in the body weight, body mass index, waist-to-hip ratio, and body fat mass values (kg, %) of the control group (P < 0.05). Th ere was no diff erence in the levels of plasma orexin A of the patients within or between groups in the pre- and poststudy measurements (P > 0.05). Th e poststudy plasma serotonin levels of the patients were lower and plasma insulin levels were higher than in the initial study (P < 0.05). Th ere was a correlation between the plasma orexin A levels and plasma n-3 fatty acids in individuals in the control group at the onset of the study (P < 0.05). Depending on the increase of the fatty acids aft er the n-3 supplementation, a correlation between plasma orexin A levels and some fatty acids was observed (P < 0.05). Conclusion: Th e data demonstrated that supplementation of n-3 fatty acid did not enhance the plasma orexin A level but did aff ect some other biochemical parameters.

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1. American Academy of Sleep Medicine. International classifi cation of sleep disorders: diagnostic and coding manual. 2nd ed. Westchester (IL): American Academy of Sleep Medicine; 2005.
2. Dauvilliers Y, Maret S, Taft i M. Genetics of normal and pathological sleep in humans. Sleep Med Rev 2005; 9: 91-100.
3. Longstreth WT Jr, Koepsell TD, Ton TG, Hendrickson AF, van Belle G. Th e epidemiology of narcolepsy. Sleep 2007; 30: 13-26.
4. Eggermann E, Serafi n M, Bayer L, Machard D, Saint-Mleux B, Jones BE et al. Orexins/hypocretins excite basal forebrain cholinergic neurons. Neuroscience 2001; 108: 177-81.
5. Dauvilliers Y, Billiard M, Montplaisir J. Clinical aspects and pathophysiology of narcolepsy. Clin Neurophysiol 2003; 114: 2000-17.
6. Zeitzer JM, Nishino S, Mignot E. Th e neurobiology of hypocretins (orexins), narcolepsy and related therapeutic interventions. Trends Pharmacol Sci 2006; 27: 368-74.
7. Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 2000; 6: 991-7.
8. Fry JM. Treatment modalities for narcolepsy. Neurology 1998; 50: 43-8.
9. De Lecea L, Sutcliff e JG. Th e hypocretins and sleep. Th e FEBS Journal 2005; 272: 5675-88.
10. Lees G, Coyne L. Th e orexins: a novel family of sleep regulating neuropeptides. Curr Anaesth Crit Care 2004; 15: 75-7.
11. Gerashchenko D, Murillo-Rodriguez E, Lin L, Xu M, Hallett L, Nishino S et al. Relationship between CSF hypocretin levels and hypocretin neuronal loss. Exp Neurol 2003; 184: 1010-6.
12. Beck B, Kozak R, Moar K, Mercer CG. Hypothalamic orexigenic peptides are overexpressed in young Long-Evans rats aft er early life exposure to fat-rich diets. Biochem Biophys Res Commun 2006; 342: 452-8.
13. Chang G, Karatayev O, Davydova Z, Leibowitz SF. Circulating triglycerides impact on orexigenic peptides and neuronal activity in hypothalamus. Endocrinology 2004; 145: 3904-12.
14. Shimokawa T, Kumar MV, Lane MD. Eff ect of a fatty acid synthase inhibitor on food intake and wxpression of hypothalamic neuropeptides. Proc Natl Acad Sci USA 2002; 99: 66-71.
15. Deckelbaum RJ, Worgall TS, Seo T. N-3 fatty acids and gene expression. Am J Clin Nutr 2006; 83: 1520-5.
16. Delion S, Chalon S, Herault J, Guilloteau E, Besnard JC, Durand G. Chronic dietary alpha-linolenic acid defi ciency alters dopaminergic and serotoninergic neurotransmission in rats. J Nutr 1994; 124: 2466-76.
17. Wortley KE, Chang GQ, Davydova Z, Leibowitz SF. Peptides that regulate food intake: orexin gene expression is increased during states of hypertriglyceridemia. Am J Physiol Regul Integr Comp Physiol 2003; 284: 1454-65.
18. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1978; 18: 499-502.
19. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-9.
20. David F, Sandra P, Wylie PL. Improving the analysis of fatty acid methyl esters using retention time locked methods and retention time databases. Agilent Technologies 2003. Available from: URL: http://www.chem.agilent.com/Library/ applications/5988-5871EN.pdf.
21. RECIPE. Serotonin in plasma. 2011. Available from: URL: http://www.recipe.de/en/products_hplc_diagn_06000.html.
22. Phoenix Pharmaceuticals. General protocol for RK-003-30. No date. Available from: URL: http://www.phoenixpeptide.com/ catalog/repository/QCdata_RIK/RK-003-30.pdf.
23. Taheri S, Zeitzer JM, Mignot E. Th e role of hypocretins (orexins) in sleep regulation and narcolepsy. Ann Rev Neurosci 2002; 25: 283-313.
24. Chabas D, Foulon C, Gonzalez J, Nasr M, Lyon-Caen O, Willer JC et al. Eating disorder and metabolism in narcoleptic patients. Sleep 2007; 30: 1267-73.
25. Williams CM, Moore F, Morgan L, Wright J. Eff ects of n-3 fatty acids on postprandial triacylglycerol and hormone concentrations in normal subjects. Br J Nutr 1992; 68: 655-66.
26. Kok SW, Overeem S, Visscher TLS, Lammers GJ, Seidell JC, Pijl H et al. Hypocretin defi ciency in narcoleptic humans is associated with abdominal obesity. Obes Res 2003; 11: 1147-54.
27. WHO/FAO. Diet, nutrition and the prevention of chronic diseases. Report of a joint WHO/FAO expert consultation. Geneva: WHO Technical Report Series, 916; 2003.
28. Dalal MA, Schuld A, Haack H, Uhr M, Geisler P, Einsensehr I et al. Normal plasma levels of orexin A (hypocretin-1) in narcoleptic patients. Neurology 2001; 56: 1749-51.
29. Nishino S, Mignot E. Article reviewed: plasma orexin-A is lower in patients with narcolepsy. Sleep Med 2002; 3: 377-8.
30. Igarashi N, Tatsumi K, Nakamura A, Sakao S, Takiguchi Y, Nishikawa T et al. Plasma orexin-A levels in obstructive sleep apnea-hypopnea syndrome. Chest 2003; 124: 1381-5.
31. Harel Z, Gascon G, Riggs S, Vaz R, Brown W, Exil G. Supplementation with omega-3 polyunsaturated fatty acids in the management of recurrent migraines in adolescents. J Adolesc Health 2002; 31: 154-61.
32. Sawazaki S, Hamazaki T, Yazawa K, Kobayashi M. Th e eff ect of docosahexaenoic acid on plasma catecholamine concentrations and glucose tolerance during long-lasting psychological stress: a double-blind placebo-controlled study. J Nutr Sci Vitaminol 1999; 45: 655-65.
33. Locke CA, Stoll AL. Omega-3 fatty acids in major depression. World Rev Nutr Diet 2001; 89: 173-85.
34. Arterburn LM, Hall EB, Oken H. Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr 2006; 83: 1467-76.
35. Tidow-Kebritchi S, Mobarhan S. Eff ects of diets containing fi sh oil and vitamin E on rheumatoid arthritis. Nutrition Review 2001; 59: 335-41.
36. Peet M, Horrobin DF. A dose-ranging study of the eff ects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry 2002; 59: 913-9.
37. Hamazaki T, Sawazaki S, Itomura M, Asaoka E, Nagao Y, Nishimura N et al. Th e eff ect of docosahexaenoic acid on aggression in young adults. J Clin Invest 1996; 97: 1129-33.
38. Dziedzic B, Szemraj J, Bartkowiak J, Walczewska A. Various dietary fats diff erentially change the gene expression of neuropeptides involved in body weight regulation in rats. J Neuroendocrinol 2007; 19: 364-73.