دوره 32، شماره 276: هفته اول اردیبهشت ماه 1393:243-255

نقش اسید های چرب امگا 3 در پیشگیری و درمان بیمار ی کبد چرب غیر الکلی

حمید ذوالفقاری, کورش جعفریان, بیژن ایرج, غلامرضا عسکری

چکیده


مقدمه: 35-10 درصد از جمعیت بزرگسالان سراسر جهان به بیماری کبد چرب غیر الکلی مبتلا می‌باشند. تا کنون هیچ درمان قطعی برای این بیماری پیشنهاد نشده است. اسیدهای چرب امگا 3 درای اثرات مفیدی در درمان هایپرلیپیدمی و بیماری‌های قلبی- عروقی می‌باشند و به تازگی برای درمان بیماری کبد چرب غیر الکلی استفاده می‌شوند. هدف از این مطالعه، مرور مطالعاتی بود كه نقش اسیدهای چرب امگا 3 در پیشگیری و درمان بیماری کبد چرب غیر الکلی را بررسی كرده بودند.

روش‌ها: ابتدا از پایگاه‌های PubMed و ISI مقالاتی كه در متن خود دارای كلمات NAFLD (Non-alcoholic fatty liver disease)، NASH (Nonalcoholic steatohepatitis)، Nonalcoholic fatty liver، Steatosis، DHA (Docosahexaenoic acid)، EPA (Eicosapentaenoic acid)، Fish oil و 3Omega  بودند، جستجو شدند. سپس مقالات به سه دسته مطالعات حیوانی، مطالعات مقطعی و مورد- شاهدی و مطالعات کارآزمایی بالینی تقسیم‌بندی شدند که در مجموع، 21 مقاله مورد ارزیابی قرار گرفتند.

یافته‌ها: نتایج مطالعات مقطعی و مورد- شاهدی همسو نبود، اما نتایج مطالعات قوی‌تر نشان می‌داد که دریافت ناکافی از منابع غذایی امگا 3 با بروز بیماری کبد چرب در ارتباط می‌باشد. بیشتر مداخلات انجام شده در مطالعات حیوانی و انسانی، تأثیر مثبتی از مصرف مکمل امگا 3 در کاهش تری گلیسیرید و چربی کبدی در مبتلایان به کبد چرب غیر الکلی گزارش کرده‌اند.

نتیجه‌گیری: کاهش دریافت امگا 3 از منابع غذایی به دلیل عادات غذایی نادرست، می‌تواند یکی از دلایل چند عاملی بودن بیماری کبد چرب باشد. همچنین مصرف مکمل آن می‌تواند در کنار اصلاح الگوی غذایی و سبک زندگی برای این بیماران مفید باشد.


واژگان کلیدی


كبد چرب غیر الكلی؛ استئاتوزیس؛ امگا 3؛ دوكوزاهگزانوئیك اسید؛ ایكوزاپنتانوئیك اسید

تمام متن:

PDF

مراجع


McCullough AJ. The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin Liver Dis 2004; 8(3): 521-33, viii.

Hegazi RA, Sutton-Tyrrell K, Evans RW, Kuller LH, Belle S, Yamamoto M, et al. Relationship of adiposity to subclinical atherosclerosis in obese patients with type 2 diabetes. Obes Res 2003; 11(12): 1597-605.

Malaguarnera L, Di RM, Zambito AM, dell'Ombra N, Di MR, Malaguarnera M. Potential role of chitotriosidase gene in nonalcoholic fatty liver disease evolution. Am J Gastroenterol 2006; 101(9): 2060-9.

Malaguarnera L, Di RM, Zambito AM, dell'Ombra N, Nicoletti F, Malaguarnera M. Chitotriosidase gene expression in Kupffer cells from patients with non-alcoholic fatty liver disease. Gut 2006; 55(9): 1313-20.

Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology 1998; 114(4): 842-5.

Malaguarnera M, Vacante M, Motta M, Malaguarnera M, Li VG, Galvano F. Effect of L-carnitine on the size of low-density lipoprotein particles in type 2 diabetes mellitus patients treated with simvastatin. Metabolism 2009; 58(11): 1618-23.

Galvano F, Li VG, Malaguarnera M, Avitabile T, Antic T, Vacante M, et al. Effects of simvastatin and carnitine versus simvastatin on lipoprotein(a) and apoprotein(a) in type 2 diabetes mellitus. Expert Opin Pharmacother 2009; 10(12): 1875-82.

Unger RH, Orci L. Lipoapoptosis: its mechanism and its diseases. Biochim Biophys Acta 2002; 1585(2-3): 202-12.

Targher G, Bertolini L, Poli F, Rodella S, Scala L, Tessari R, et al. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes 2005; 54(12): 3541-6.

Shimabukuro M, Zhou YT, Levi M, Unger RH. Fatty acid-induced beta cell apoptosis: a link between obesity and diabetes. Proc Natl Acad Sci U S A 1998; 95(5): 2498-502.

de Almeida IT, Cortez-Pinto H, Fidalgo G, Rodrigues D, Camilo ME. Plasma total and free fatty acids composition in human non-alcoholic steatohepatitis. Clin Nutr 2002; 21(3): 219-23.

Yki-Jarvinen H. Nutritional modulation of nonalcoholic fatty liver disease and insulin resistance: human data. Curr Opin Clin Nutr Metab Care 2010; 13(6): 709-14.

Bedogni G, Bellentani S. Fatty liver: how frequent is it and why? Ann Hepatol 2004; 3(2): 63-5.

Shapiro H, Tehilla M, Attal-Singer J, Bruck R, Luzzatti R, Singer P. The therapeutic potential of long-chain omega-3 fatty acids in nonalcoholic fatty liver disease. Clin Nutr 2011; 30(1): 6-19.

Henkel J, Frede K, Schanze N, Vogel H, Schurmann A, Spruss A, et al. Stimulation of fat accumulation in hepatocytes by PGE(2)-dependent repression of hepatic lipolysis, beta-oxidation and VLDL-synthesis. Lab Invest 2012; 92(11): 1597-606.

Owen JL, Zhang Y, Bae SH, Farooqi MS, Liang G, Hammer RE, et al. Insulin stimulation of SREBP-1c processing in transgenic rat hepatocytes requires p70 S6-kinase. Proc Natl Acad Sci U S A 2012; 109(40): 16184-9.

Zhang J, Tan Y, Yao F, Zhang Q. Polydatin alleviates non-alcoholic fatty liver disease in rats by inhibiting the expression of TNF-alpha and SREBP-1c. Mol Med Rep 2012; 6(4): 815-20.

Porter JR, Lee CY, Espenshade PJ, Iglesias PA. Regulation of SREBP during hypoxia requires Ofd1-mediated control of both DNA binding and degradation. Mol Biol Cell 2012; 23(18): 3764-74.

Akarte AS, Srinivasan BP, Gandhi S. Vildagliptin selectively ameliorates GLP-1, GLUT4, SREBP-1c mRNA levels and stimulates beta-cell proliferation resulting in improved glucose homeostasis in rats with streptozotocin-induced diabetes. J Diabetes Complications 2012; 26(4): 266-74.

Yahagi N, Shimano H, Hasty AH, Amemiya-Kudo M, Okazaki H, Tamura Y, et al. A crucial role of sterol regulatory element-binding protein-1 in the regulation of lipogenic gene expression by polyunsaturated fatty acids. J Biol Chem 1999; 274(50): 35840-4.

Shao W, Espenshade PJ. Expanding roles for SREBP in metabolism. Cell Metab 2012; 16(4): 414-9.

Levy JR, Clore JN, Stevens W. Dietary n-3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats. Hepatology 2004; 39(3): 608-16.

Svegliati-Baroni G, Candelaresi C, Saccomanno S, Ferretti G, Bachetti T, Marzioni M, et al. A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-alpha and n-3 polyunsaturated fatty acid treatment on liver injury. Am J Pathol 2006; 169(3): 846-60.

Buettner R, Parhofer KG, Woenckhaus M, Wrede CE, Kunz-Schughart LA, Scholmerich J, et al. Defining high-fat-diet rat models: metabolic and molecular effects of different fat types. J Mol Endocrinol 2006; 36(3): 485-501.

Shirouchi B, Nagao K, Inoue N, Ohkubo T, Hibino H, Yanagita T. Effect of dietary omega 3 phosphatidylcholine on obesity-related disorders in obese Otsuka Long-Evans Tokushima fatty rats. J Agric Food Chem 2007; 55(17): 7170-6.

Sekiya M, Yahagi N, Matsuzaka T, Najima Y, Nakakuki M, Nagai R, et al. Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology 2003; 38(6): 1529-39.

El-Badry AM, Moritz W, Contaldo C, Tian Y, Graf R, Clavien PA. Prevention of reperfusion injury and microcirculatory failure in macrosteatotic mouse liver by omega-3 fatty acids. Hepatology 2007; 45(4): 855-63.

Martin PG, Guillou H, Lasserre F, Dejean S, Lan A, Pascussi JM, et al. Novel aspects of PPARalpha-mediated regulation of lipid and xenobiotic metabolism revealed through a nutrigenomic study. Hepatology 2007; 45(3): 767-77.

Gonzalez-Periz A, Horrillo R, Ferre N, Gronert K, Dong B, Moran-Salvador E, et al. Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J 2009; 23(6): 1946-57.

Capristo E, Miele L, Forgione A, Vero V, Farnetti S, Mingrone G, et al. Nutritional aspects in patients with non-alcoholic steatohepatitis (NASH). Eur Rev Med Pharmacol Sci 2005; 9(5): 265-8.

Cortez-Pinto H, Jesus L, Barros H, Lopes C, Moura MC, Camilo ME. How different is the dietary pattern in non-alcoholic steatohepatitis patients? Clin Nutr 2006; 25(5): 816-23.

Toshimitsu K, Matsuura B, Ohkubo I, Niiya T, Furukawa S, Hiasa Y, et al. Dietary habits and nutrient intake in non-alcoholic steatohepatitis. Nutrition 2007; 23(1): 46-52.

Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R, Webb M, Blendis L, Halpern Z, et al. Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): a population based study. J Hepatol 2007; 47(5): 711-7.

Kim CH, Kallman JB, Bai C, Pawloski L, Gewa C, Arsalla A, et al. Nutritional assessments of patients with non-alcoholic fatty liver disease. Obes Surg 2010; 20(2): 154-60.

Shi L, Liu ZW, Li Y, Gong C, Zhang H, Song LJ, et al. The prevalence of nonalcoholic fatty liver disease and its association with lifestyle/dietary habits among university faculty and staff in Chengdu. Biomed Environ Sci 2012; 25(4): 383-91.

Capanni M, Calella F, Biagini MR, Genise S, Raimondi L, Bedogni G, et al. Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study. Aliment Pharmacol Ther 2006; 23(8): 1143-51.

Itoh M, Suganami T, Satoh N, Tanimoto-Koyama K, Yuan X, Tanaka M, et al. Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Arterioscler Thromb Vasc Biol 2007; 27(9): 1918-25.

Spadaro L, Magliocco O, Spampinato D, Piro S, Oliveri C, Alagona C, et al. Effects of n-3 polyunsaturated fatty acids in subjects with nonalcoholic fatty liver disease. Dig Liver Dis 2008; 40(3): 194-9.

Tanaka N, Sano K, Horiuchi A, Tanaka E, Kiyosawa K, Aoyama T. Highly purified eicosapentaenoic acid treatment improves nonalcoholic steatohepatitis. J Clin Gastroenterol 2008; 42(4): 413-8.

Sofi F, Giangrandi I, Cesari F, Corsani I, Abbate R, Gensini GF, et al. Effects of a 1-year dietary intervention with n-3 polyunsaturated fatty acid-enriched olive oil on non-alcoholic fatty liver disease patients: a preliminary study. Int J Food Sci Nutr 2010; 61(8): 792-802.

Nobili V, Bedogni G, Alisi A, Pietrobattista A, Rise P, Galli C, et al. Docosahexaenoic acid supplementation decreases liver fat content in children with non-alcoholic fatty liver disease: double-blind randomised controlled clinical trial. Arch Dis Child 2011; 96(4): 350-3.




Creative Commons Attribution-NonCommercial 4.0

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.