Özet
Erdem N.B., Effect of Reduced Saturated Fatty Acid Diet on Inflammation in Non-AlcoholicFatty Liver Disease (NAFLD), Hacettepe University Institue of Health Sciences of Nutritional Sciences, Master of Sciences Thesis, Ankara, 2017.Non-Alcoholic Fatty Liver Disease (NAFLD) is a complex disease that includes from; stetatosis known as a simple fatty liver to Non-Alcoholic Steatohepatitis, having inflamatuar situation and liver cancer.It has been showed that both of fat type and amount plays pioner role at the progression of disease.The aim of this study is to determine effect of reduced saturated fatty acids diet in anthropometric measurements some of biochemical parameters in blood Tumor necrosis factor (TNF) -α, Interleukin (IL)-6 and Chemerin levels in serum in individuals with NAFLD. A total of 23 adults aged between 19 to 65 years participated in the study. In this study regard individuals were randomly dividided into two groups. They followed diet therapy for three months; group with 7 % saturated fatty acid (n=11) 12% saturated fatty acid (n=12). Questionnairre including demographic characteristics,dietary habits, smoking status, alcohol consumption and 24 hour physical activity recall,were applied face to face at baseline. Collected serum samples for TNF-α, IL-6 and chemerin were run in by ELISA. Data of individiuals’s anthropometric measurements, biochemical parameters and serum protein levels were compared at baseline and end of study. Body Mass Index (BMI) decreased from 31,2±3,96 kg〖/m〗^2 to 29,3±4,36 kg〖/m〗^2(p=0,002) in 7 % saturated fatty acid group and from 29,9±3,90 kg〖/m〗^2 to 28,8±3,72kg〖/m〗^2 in 12 % saturated fatty acid group. (p=0,001)These changes were siginificant in statistically. At the end of study ALT, AST, enzyme level changes were significant (p<0,05). In both groups body weight, waist circumference and body fat percentage changes were significant in statistically (p<0,05). However TNF-α, IL-6 and chemerin levels changes weren’t significant in statistically (p>0,05). As a part of routin therapy importance of healthy nutrition should be explained to patients with NAFLD. Healhty nutrition habits can be applied long life should be aimed to patients with NAFLD.
Künye
1. Stojsavljevic S, Gomercic Palcic M, Virovic Jukic L, Smircic Duvnjak L, Duvnjak M. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(48):18070-91.
2. Finelli C, Tarantino G. What is the role of adiponectin in obesity related non-alcoholic fatty liver disease? World J Gastroenterol. 2013;19(6):802-12.
3. Fazel Y, Koenig AB, Sayiner M, Goodman ZD, Younossi ZM. Epidemiology and natural history of non-alcoholic fatty liver disease. Metabolism. 2016;65(8):1017-25.
4. Dietrich P, Hellerbrand C. Non-alcoholic fatty liver disease, obesity and the metabolic syndrome. Best Pract Res Clin Gastroenterol. 2014;28(4):637-53.
5. Basaranoglu M, Basaranoglu G, Senturk H. From fatty liver to fibrosis: a tale of "second hit". World J Gastroenterol. 2013;19(8):1158-65.
6. Smith U, Andersson CX, Gustafson B, Hammarstedt A, Isakson P, Wallerstedt E. Adipokines, systemic inflammation and inflamed adipose tissue in obesity and insulin resistance. Int Congr Ser. 2007;1303(2007):31-34 .
7. Tordjman J, Guerre-Millo M, Clement K. Adipose tissue inflammation and liver pathology in human obesity. Diabetes Metab. 2008;34(6):658-63.
8. Kalafateli M, Triantos C, Tsochatzis E, Michalaki M, Koutroumpakis E, Thomopoulos K, et al. Adipokines levels are associated with the severity of liver disease in patients with alcoholic cirrhosis. World J Gastroenterol. 2015;21(10):3020-9.
9. Braunersreuther V, Viviani GL, Mach F, Montecucco F. Role of cytokines and chemokines in non-alcoholic fatty liver disease. World J Gastroenterol. 2012;18(8):727-35.
10. Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes. 2007;56(4):1010-3.
11. Polyzos SA, Kountouras J, Mantzoros CS. Adipokines in nonalcoholic fatty liver disease. Metabolism. 2016;65(8):1062-79.
12. Larter CZ, Farrell GC. Insulin resistance, adiponectin, cytokines in NASH: Which is the best target to treat? J Hepatol. 2006;44(2):253-61.
13. Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology. 2007;132(6):2169-80.
14. Tsochatzis E, Papatheodoridis GV, Archimandritis AJ. The evolving role of leptin and adiponectin in chronic liver diseases. Am J Gastroenterol. 2006;101(11):2629-40.
15. Tarantino G, Savastano S, Colao A. Hepatic steatosis, low-grade chronic inflammation and hormone/growth factor/adipokine imbalance. World J Gastroenterol. 2010;16(38):4773-83.
16. Duarte N, Coelho IC, Patarrão RS, Almeida JI, Penha-Gonçalves C, Macedo MP. How inflammation impinges on NAFLD: a role for Kupffer cells. BioMed Res Int. 2015;2015.
17. Li Y, Liu L, Wang B, Wang J, Chen D. Simple steatosis is a more relevant source of serum inflammatory markers than omental adipose tissue. Clin Res Hepatol Gastroenterol. 2014;38(1):46-54.
18. Hatziagelaki E, Herder C, Tsiavou A, Teichert T, Chounta A, Nowotny P, et al. Serum chemerin concentrations associate with beta-cell function, but not with insulin resistance in individuals with non-alcoholic fatty liver disease (NAFLD). PLoS One. 2015;10(5):e0124935.
19. Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, et al. Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology. 2007;148(10):4687-94.
20. Krautbauer S, Wanninger J, Eisinger K, Hader Y, Beck M, Kopp A, et al. Chemerin is highly expressed in hepatocytes and is induced in non-alcoholic steatohepatitis liver. Exp Mol Pathol. 2013;95(2):199-205.
21. Parlee SD, Ernst MC, Muruganandan S, Sinal CJ, Goralski KB. Serum chemerin levels vary with time of day and are modified by obesity and tumor necrosis factor-{alpha}. Endocrinology. 2010;151(6):2590-602.
22. Goralski KB, McCarthy TC, Hanniman EA, Zabel BA, Butcher EC, Parlee SD, et al. Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem. 2007;282(38):28175-88.
23. Catalán V, Gómez-Ambrosi J, Rodríguez A, Ramírez B, Rotellar F, Valentí V, et al. Increased levels of chemerin and its receptor, chemokine-like receptor-1, in obesity are related to inflammation: tumor necrosis factor-α stimulates mRNA levels of chemerin in visceral adipocytes from obese patients. Surg Obes Relat Dis. 2013;9(2):306-14.
24. Weigert J, Neumeier M, Wanninger J, Filarsky M, Bauer S, Wiest R, et al. Systemic chemerin is related to inflammation rather than obesity in type 2 diabetes. Clin Endocrinol (Oxf). 2010;72(3):342-8.
25. Lehrke M, Becker A, Greif M, Stark R, Laubender RP, von Ziegler F, et al. Chemerin is associated with markers of inflammation and components of the metabolic syndrome but does not predict coronary atherosclerosis. Eur J Endocrinol. 2009;161(2):339-44.
26. Sell H, Divoux A, Poitou C, Basdevant A, Bouillot J-L, Bedossa P, et al. Chemerin correlates with markers for fatty liver in morbidly obese patients and strongly decreases after weight loss induced by bariatric surgery. J Clin Endocrinol Metab. 2010;95(6):2892-6.
27. Mussig K, Staiger H, Machicao F, Thamer C, Machann J, Schick F, et al. RARRES2, encoding the novel adipokine chemerin, is a genetic determinant of disproportionate regional body fat distribution: a comparative magnetic resonance imaging study. Metabolism. 2009;58(4):519-24.
28. Kukla M, Zwirska-Korczala K, Hartleb M, Waluga M, Chwist A, Kajor M, et al. Serum chemerin and vaspin in non-alcoholic fatty liver disease. Scand J Gastroenterol. 2010;45(2):235-42.
29. Tilg H. The role of cytokines in non-alcoholic fatty liver disease. Dig Dis. 2010;28(1):179-85.
30. Jamali R, Razavizade M, Arj A, Aarabi MH. Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease. World J Gastroenterol. 2016;22(21):5096.
31. Polyzos S, Kountouras J, Zavos C. The multi-hit process and the antagonistic roles of tumor necrosis factor-alpha and adiponectin in non alcoholic fatty liver disease. Hippokratia. 2009;13(2):127.
32. Tilg H, Hotamisligil GS. Nonalcoholic fatty liver disease: cytokine-adipokine interplay and regulation of insulin resistance. Gastroenterology. 2006;131(3):934-45.
33. Wullaert A, van Loo G, Heyninck K, Beyaert R. Hepatic tumor necrosis factor signaling and nuclear factor-κB: effects on liver homeostasis and beyond. Endocr Rev. 2007;28(4):365-86.
34. Satapathy SK, Garg S, Chauhan R, Sakhuja P, Malhotra V, Sharma BC, et al. Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. Am J Gastroenterol. 2004;99(10):1946-52.
35. Plomgaard P, Bouzakri K, Krogh-Madsen R, Mittendorfer B, Zierath JR, Pedersen BK. Tumor necrosis factor-α induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation. Diabetes. 2005;54(10):2939-45.
36. Rotter V, Nagaev I, Smith U. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-α, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem. 2003;278(46):45777-84.
37. Tokushige K, Takakura M, Tsuchiya-Matsushita N, Taniai M, Hashimoto E, Shiratori K. Influence of TNF gene polymorphisms in Japanese patients with NASH and simple steatosis. J Hepatol. 2007;46(6):1104-10.
38. Lemoine M, Ratziu V, Kim M, Maachi M, Wendum D, Paye F, et al. Serum adipokine levels predictive of liver injury in non‐alcoholic fatty liver disease. Liver Int. 2009;29(9):1431-8.
39. Carulli L, Canedi I, Rondinella S, Lombardini S, Ganazzi D, Fargion S, et al. Genetic polymorphisms in non-alcoholic fatty liver disease: interleukin-6-174G/C polymorphism is associated with non-alcoholic steatohepatitis. Dig Liver Dis. 2009;41(11):823-8.
40. Tarantino G, Conca P, Pasanisi F, Ariello M, Mastrolia M, Arena A, et al. Could inflammatory markers help diagnose nonalcoholic steatohepatitis? Eur J Gastroenterol Hepatol. 2009;21(5):504-11.
41. Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J. Beyond insulin resistance in NASH: TNF‐α or adiponectin? Hepatology. 2004;40(1):46-54.
42. Genc H, Dogru T, Kara M, Tapan S, Ercin CN, Acikel C, et al. Association of plasma visfatin with hepatic and systemic inflammation in nonalcoholic fatty liver disease. Ann Hepatol. 2013;12(4):548-55.
43. Kukla M, Ciupinska-Kajor M, Kajor M, Wylezol M, Zwirska-Korczala K, Hartleb M, et al. Liver visfatin expression in morbidly obese patients with nonalcoholic fatty liver disease undergoing bariatric surgery. Pol J Pathol. 2010;61(3):147-53.
44. Aller R, De Luis D, Izaola O, Sagrado MG, Conde R, Velasco M, et al. Influence of visfatin on histopathological changes of non-alcoholic fatty liver disease. Dig Dis Sci. 2009;54(8):1772-77.
45. Tsutsumi C, Okuno M, Tannous L, Piantedosi R, Allan M, Goodman D, et al. Retinoids and retinoid-binding protein expression in rat adipocytes. J Biol Chem. 1992;267(3):1805-10.
46. Chang X, Yan H, Bian H, Xia M, Zhang L, Gao J, et al. Serum retinol binding protein 4 is associated with visceral fat in human with nonalcoholic fatty liver disease without known diabetes: a cross-sectional study. Lipids Health Dis. 2015;14(28):1-8
47. Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Schleicher E, et al. High circulating retinol-binding protein 4 is associated with elevated liver fat but not with total, subcutaneous, visceral, or intramyocellular fat in humans. Diabetes Care. 2007;30(5):1173-8.
48. Polyzos SA, Aronis KN, Kountouras J, Raptis DD, Vasiloglou MF, Mantzoros CS. Circulating leptin in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Diabetologia. 2016;59(1):30-43.
49. Kelesidis T, Kelesidis I, Chou S, Mantzoros CS. Narrative review: the role of leptin in human physiology: emerging clinical applications. Ann Intern Med. 2010;152(2):93-100.
50. Dalamaga M, Chou SH, Shields K, Papageorgiou P, Polyzos SA, Mantzoros CS. Leptin at the intersection of neuroendocrinology and metabolism: current evidence and therapeutic perspectives. Cell Metab. 2013;18(1):29-42.
51. Frank S, Stallmeyer B, Kämpfer H, Kolb N, Pfeilschifter J. Leptin enhances wound re-epithelialization and constitutes a direct function of leptin in skin repair. J Clin Invest. 2000;106(4):501-9.
52. Angulo P, Alba LM, Petrovic LM, Adams LA, Lindor KD, Jensen MD. Leptin, insulin resistance, and liver fibrosis in human nonalcoholic fatty liver disease. J Hepatol. 2004;41(6):943-9.
53. Polyzos SA, Toulis KA, Goulis DG, Zavos C, Kountouras J. Serum total adiponectin in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Metabolism. 2011;60(3):313-26.
54. Melgar-Lesmes P, Casals G, Pauta M, Ros J, Reichenbach V, Bataller R, et al. Apelin mediates the induction of profibrogenic genes in human hepatic stellate cells. Endocrinology. 2010;151(11):5306-14.
55. Hashım AM, Ali G, Hassan H, El-Sayed A, Amro Ayad M. Serum Apelin Level and Insulin Resistance in Nonalcoholic Fatty Liver Disease and their Relationship to Histological Severity of Liver Disease. Med J Cairo Univ. 2014;82(1):363-368
56. García-Díaz D, Campión J, Milagro FI, Martínez JA. Adiposity dependent apelin gene expression: relationships with oxidative and inflammation markers. Mol Cell Biochem. 2007;305(1-2):87-94.
57. Shen C, Zhao C-Y, Wang W, Wang Y-D, Sun H, Cao W, et al. The relationship between hepatic resistin overexpression and inflammation in patients with nonalcoholic steatohepatitis. BMC Gastroenterol. 2014;14(39):1-8
58. Bajaj M, Suraamornkul S, Hardies L, Pratipanawatr T, DeFronzo R. Plasma resistin concentration, hepatic fat content, and hepatic and peripheral insulin resistance in pioglitazone-treated type II diabetic patients. Int J Obes. 2004;28(6):783-9.
59. Jarrar M, Baranova A, Collantes R, Ranard B, Stepanova M, Bennett C, et al. Adipokines and cytokines in non‐alcoholic fatty liver disease. Aliment Pharmacol Ther. 2008;27(5):412-21.
60. Lottenberg AM, Afonso Mda S, Lavrador MS, Machado RM, Nakandakare ER. The role of dietary fatty acids in the pathology of metabolic syndrome. J Nutr Biochem. 2012;23(9):1027-40.
61. Obesity and overweight [İnternet]. 2008. [Erişim Tarihi 17 Nisan 2017]. Erişim adresi http://www.wiredhealthresources.net/resources/
62. Guan YS, He Q. A current update on the rule of alternative and complementary medicine in the treatment of liver diseases. Evid Based Complement Alternat Med. 2013;2013:321234.
63. Aller R, de Luis DA, Izaola O, de la Fuente B, Bachiller R. Effect of a high monounsaturated vs high polyunsaturated fat hypocaloric diets in nonalcoholic fatty liver disease. Eur Rev Med Pharmacol Sci. 2014;18(7):1041-7.
64. Frayn KN. Adipose tissue as a buffer for daily lipid flux. Diabetologia. 2002;45(9):1201-10.
65. Yki-Jarvinen H. Liver fat in the pathogenesis of insulin resistance and type 2 diabetes. Dig Dis. 2010;28(1):203-9.
66. Green CJ, Hodson L. The influence of dietary fat on liver fat accumulation. Nutrients. 2014;6(11):5018-33.
67. Partridge CG, Fawcett GL, Wang B, Semenkovich CF, Cheverud JM. The effect of dietary fat intake on hepatic gene expression in LG/J AND SM/J mice. BMC Genomics. 2014;15:99.
68. Zelber-Sagi S, Godos J, Salomone F. Lifestyle changes for the treatment of nonalcoholic fatty liver disease: a review of observational studies and intervention trials. Therap Adv Gastroenterol. 2016;9(3):392-407.
69. McCarthy EM, Rinella ME. The role of diet and nutrient composition in nonalcoholic Fatty liver disease. J Acad Nutr Diet. 2012;112(3):401-9.
70. Papandreou D, Andreou E. Role of diet on non-alcoholic fatty liver disease: An updated narrative review. World J Hepatol. 2015;7(3):575-82.
71. Asrih M, Jornayvaz FR. Diets and nonalcoholic fatty liver disease: the good and the bad. Clin Nutr. 2014;33(2):186-90.
72. Byrne CD. Fatty liver: role of inflammation and fatty acid nutrition. Prostaglandins Leukot Essent Fatty Acids. 2010;82(4-6):265-71.
73. Juarez-Hernandez E, Chavez-Tapia NC, Uribe M, Barbero-Becerra VJ. Role of bioactive fatty acids in nonalcoholic fatty liver disease. Nutr J. 2016;15(1):72.
74. Ferramosca A, Zara V. Modulation of hepatic steatosis by dietary fatty acids. World J Gastroenterol. 2014;20(7):1746-55.
75. Marina A, von Frankenberg AD, Suvag S, Callahan HS, Kratz M, Richards TL, et al. Effects of dietary fat and saturated fat content on liver fat and markers of oxidative stress in overweight/obese men and women under weight-stable conditions. Nutrients. 2014;6(11):4678-90.
76. Besler HT, Rakıcıoğlu N, Ayaz A, Büyüktuncer-Demirel Z, Gökmen-Özel H, Eroğlu-Samur G. Türkiye'ye Özgü Besin ve Beslenme Rehberi. Ankara; 2015
77. Wang D, Wei Y, Pagliassotti MJ. Saturated fatty acids promote endoplasmic reticulum stress and liver injury in rats with hepatic steatosis. Endocrinology. 2006;147(2):943-51.
78. Hardy S, El-Assaad W, Przybytkowski E, Joly E, Prentki M, Langelier Y. Saturated fatty acid-induced apoptosis in MDA-MB-231 breast cancer cells. A role for cardiolipin. J Biol Chem. 2003;278(34):31861-70.
79. Wei Y, Wang D, Topczewski F, Pagliassotti MJ. Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am J Physiol Endocrinol Metab. 2006;291(2):E275-81.
80. Spritz N, Mishkel MA. Effects of dietary fats on plasma lipids and lipoproteins: an hypothesis for the lipid-lowering effect of unsaturated fatty acids. J Clin Invest. 1969;48(1):78-86.
81. Tripodi A, Loria P, Dilengite MA, Carulli N. Effect of fish oil and coconut oil diet on the LDL receptor activity of rat liver plasma membranes. Biochim Biophys Acta. 1991;1083(3):298-304.
82. Assy N, Nassar F, Nasser G, Grosovski M. Olive oil consumption and non-alcoholic fatty liver disease. World J Gastroenterol. 2009;15(15):1809-15.
83. Sato K, Arai H, Mizuno A, Fukaya M, Sato T, Koganei M, et al. Dietary palatinose and oleic acid ameliorate disorders of glucose and lipid metabolism in Zucker fatty rats. J Nutr. 2007;137(8):1908-15.
84. Esposito K, Giugliano D. Mediterranean dietary patterns and chronic diseases. Am J Clin Nutr. 2008;88(4):1179-80; author reply 80-1.
85. Ruiz-Gutierrez V, Perez-Espinosa A, Vazquez CM, Santa-Maria C. Effects of dietary fats (fish, olive and high-oleic-acid sunflower oils) on lipid composition and antioxidant enzymes in rat liver. Br J Nutr. 1999;82(3):233-41.
86. Türkiye'ye Özgü Beslenme Rehberi 2004 [Erişim Tarihi 17 Nisan 2017]. Erişim adresi: http://www.bdb.hacettepe.edu.tr/torehberi.pdf.
87. Jump DB, Depner CM, Tripathy S, Lytle KA. Potential for dietary omega-3 fatty acids to prevent nonalcoholic fatty liver disease and reduce the risk of primary liver cancer. Adv Nutr. 2015;6(6):694-702.
88. Li YH, Yang LH, Sha KH, Liu TG, Zhang LG, Liu XX. Efficacy of poly-unsaturated fatty acid therapy on patients with nonalcoholic steatohepatitis. World J Gastroenterol. 2015;21(22):7008-13.
89. Calzolari I, Fumagalli S, Marchionni N, Di Bari M. Polyunsaturated fatty acids and cardiovascular disease. Curr Pharm Des. 2009;15(36):4094-102.
90. Da Silva HE, Arendt BM, Noureldin SA, Therapondos G, Guindi M, Allard JP. A cross-sectional study assessing dietary intake and physical activity in Canadian patients with nonalcoholic fatty liver disease vs healthy controls. J Acad Nutr Diet. 2014;114(8):1181-94.
91. Provenzano A, Milani S, Vizzutti F, Delogu W, Navari N, Novo E, et al. n-3 polyunsaturated fatty acids worsen inflammation and fibrosis in experimental nonalcoholic steatohepatitis. Liver Int. 2014;34(6):918-30.
92. Dentin R, Girard J, Postic C. Carbohydrate responsive element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c): two key regulators of glucose metabolism and lipid synthesis in liver. Biochimie. 2005;87(1):81-6.
93. Jump DB. N-3 polyunsaturated fatty acid regulation of hepatic gene transcription. Curr Opin Lipidol. 2008;19(3):242-7.
94. 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.
95. Popescu LA, Virgolici B, Lixandru D, Miricescu D, Condrut E, Timnea O, et al. Effect of diet and omega-3 fatty acids in NAFLD. Rom J Morphol Embryol. 2013;54(3 Suppl):785-90.
96. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55(6):2005-23.
97. Valenzuela R, Videla LA. The importance of the long-chain polyunsaturated fatty acid n-6/n-3 ratio in development of non-alcoholic fatty liver associated with obesity. Food Funct. 2011;2(11):644-8.
98. 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.
99. Allard JP, Aghdassi E, Mohammed S, Raman M, Avand G, Arendt BM, et al. Nutritional assessment and hepatic fatty acid composition in non-alcoholic fatty liver disease (NAFLD): a cross-sectional study. J Hepatol. 2008;48(2):300-7.
100. FAO. Human energy requirements report, Rome: 2001 17–24 October.
101. Baysal A, Aksoy M, Besler HT, Bozkurt N, Keçecioğlu S, Mercanlıgil SM ve ark. Diyet El Kitabı. 6. baskı. Ankara: Hatiboğlu Basım ve Yayım San. Tic. Ltd. Şti. . Diyet El Kitabı 2011.
102. Harris JA, Benedict FG. A biometric study of human basal metabolism. Proc Natl Acad Sci U.S.A 1918;4(12):370-3.
103. Amiri HL, Agah S, Azar JT, Hosseini S, Shidfar F, Mousavi SN. Effect of daily calcitriol supplementation with and without calcium on disease regression in non-alcoholic fatty liver patients following an energy-restricted diet: Randomized, controlled, double-blind trial. Clin Nutr. 2016.
104. Waist Circumference and Waist–Hip Ratio Report. Geneva: World Helath Organization; 2008 December 8-11.
105. Fan S, Yang B, Zhi X, He J, Ma P, Yu L, et al. Neck circumference associated with arterial blood pressures and hypertension: A cross-sectional community-based study in northern Han Chinese.(İnternet). 2017 [Erişim Tarihi 10 Temmuz 2017]. Erişim adresi: https://www.nature.com/articles/
106. Pimenta NM, Santa-Clara H, Melo X, Cortez-Pinto H, Silva-Nunes J, Sardinha LB. Waist-to-Hip Ratio Is Related to Body Fat Content and Distribution Regardless of the Waist Circumference Measurement Protocol in Nonalcoholic Fatty Liver Disease Patients. Int J Sport Nutr Exerc Metab. 2016;26(4):307-14.
107. Mason C, Katzmarzyk PT. Effect of the site of measurement of waist circumference on the prevalence of the metabolic syndrome. Am J of Cardiol. 2009;103(12):1716-20.
108. 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(7):412-9.
109. Gelli C, Tarocchi M, Abenavoli L, Di Renzo L, Galli A, De Lorenzo A. Effect of a counseling-supported treatment with the Mediterranean diet and physical activity on the severity of the non-alcoholic fatty liver disease. World J Gastroenterol. 2017;23(17):3150-62.
110. Leslie T, Pawloski L, Kallman-Price J, Escheik C, Hossain N, Fang Y, et al. Survey of health status, nutrition and geography of food selection of chronic liver disease patients. Ann Hepatol. 2014;13(5):533-40.
111. Non-Alcoholic Fatty Liver Disease (NAFLD) 2016 [Erişim Tarihi 24 Temmuz 2017]. Erişim adresi: http://www.liverfoundation.org/abouttheliver/info/nafld/
112. Perseghin G, Lattuada G, De Cobelli F, Ragogna F, Ntali G, Esposito A, et al. Habitual physical activity is associated with intrahepatic fat content in humans. Diabetes Care. 2007;30(3):683-8.
113. Magkos F. Exercise and fat accumulation in the human liver. Curr Opin Lipidol. 2010;21(6):507-17.
114. Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R, Webb M, Zvibel I, Goldiner I, et al. Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study. Hepatology. 2008;48(6):1791-8.
115. Ueno T, Sugawara H, Sujaku K, Hashimoto O, Tsuji R, Tamaki S, et al. Therapeutic effects of restricted diet and exercise in obese patients with fatty liver. J Hepatol. 1997;27(1):103-7.
116. Szalman K, Bancu L, Sin A. Correlations between anthropometric and serologic elements of metabolic syndrome and histopathologic features of nonalcoholic fatty liver disease. Rom J Morphol Embryol. 2013;54(1):173-8.
117. Executive summary of the clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. Arch Intern Med. 1998;158(17):1855-67.
118. Rusu E, Enache G, Jinga M, Dragut R, Nan R, Popescu H, et al. Medical nutrition therapy in non-alcoholic fatty liver disease--a review of literature. J Med Life. 2015;8(3):258-62.
119. Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010;51(1):121-9.
120. Rodriguez-Hernandez H, Cervantes-Huerta M, Rodriguez-Moran M, Guerrero-Romero F. Decrease of aminotransferase levels in obese women is related to body weight reduction, irrespective of type of diet. Ann Hepatol. 2011;10(4):486-92.
121. Cuthbertson DJ, Shojaee-Moradie F, Sprung VS, Jones H, Pugh CJ, Richardson P, et al. Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease. Clin Sci (Lond). 2016;130(2):93-104.
122. Li Q, Wang N, Han B, Chen Y, Zhu C, Chen Y, et al. Neck circumference as an independent indicator to non-alcoholic fatty liver disease in non-obese men. Nutr Metab (Lond). 2015;12:63.
123. Baloseanu CL, Streba CT, Vere CC, Comanescu V, Rogoveanu I. Association between liver histology, carotid ultrasonography and retinal vascular changes in patients with nonalcoholic fatty liver disease (NAFLD). Rom J Morphol Embryol. 2012;53(3):609-14.
124. Yamamoto M, Iwasa M, Iwata K, Kaito M, Sugimoto R, Urawa N, et al. Restriction of dietary calories, fat and iron improves non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2007;22(4):498-503.
125. Ryan MC, Abbasi F, Lamendola C, Carter S, McLaughlin TL. Serum alanine aminotransferase levels decrease further with carbohydrate than fat restriction in insulin-resistant adults. Diabetes Care. 2007;30(5):1075-80.
126. Utzschneider KM, Bayer-Carter JL, Arbuckle MD, Tidwell JM, Richards TL, Craft S. Beneficial effect of a weight-stable, low-fat/low-saturated fat/low-glycaemic index diet to reduce liver fat in older subjects. Br J Nutr. 2013;109(6):1096-104.
127. Larson-Meyer DE, Newcomer BR, Heilbronn LK, Volaufova J, Smith SR, Alfonso AJ, et al. Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function. Obesity (Silver Spring). 2008;16(6):1355-62.
128. Westerbacka J, Lammi K, Hakkinen AM, Rissanen A, Salminen I, Aro A, et al. Dietary fat content modifies liver fat in overweight nondiabetic subjects. J Clin Endocrinol Metab. 2005;90(5):2804-9.
129. Diabetes Management Guidelines [İnternet) 2016 [Erişim Tarihi 24 Temmuz 2017]. Erişim adresi: http://www.ndei.org/ADA-nutrition-guidelines-2013.aspx.html
130. Saturated Fats 2015 [İnternet) [Erişim Tarihi 24 Temmuz 2017) Erişim adresi: https://healthyforgood.heart.org/Eat-smart/Articles/Saturated-Fats.
131. The American Heart Association's Diet and Lifestyle Recommendations 2015 [Erişim Tarihi 24 Temmuz 2017]. Erişim adresi: http://www.heart.org/HEARTORG/HealthyLiving/Diet-and-Lifestyle-Recommendations_UCM_305855_Article.jsp#.WXWkgxXygdU.
132. Chalasani NP, Sanyal AJ, Kowdley KV, Robuck PR, Hoofnagle J, Kleiner DE, et al. Pioglitazone versus vitamin E versus placebo for the treatment of non-diabetic patients with non-alcoholic steatohepatitis: PIVENS trial design. Contemp Clin Trials. 2009;30(1):88-96.
133. Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA. 2011;305(16):1659-68.
134. Chan DC, Watts GF, Gan S, Wong AT, Ooi EM, Barrett PH. Nonalcoholic fatty liver disease as the transducer of hepatic oversecretion of very-low-density lipoprotein-apolipoprotein B-100 in obesity. Arterioscler Thromb Vasc Biol. 2010;30(5):1043-50.
135. Jamali R, Razavizade M, Arj A, Aarabi MH. Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease. World J Gastroenterol. 2016;22(21):5096-103.
136. Rotter V, Nagaev I, Smith U. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem. 2003;278(46):45777-84.
137. Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab. 1998;83(3):847-50.
138. Bozaoglu K, Segal D, Shields KA, Cummings N, Curran JE, Comuzzie AG, et al. Chemerin is associated with metabolic syndrome phenotypes in a Mexican-American population. J Clin Endocrinol Metab. 2009;94(8):3085-8.
139. Chakaroun R, Raschpichler M, Kloting N, Oberbach A, Flehmig G, Kern M, et al. Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism. 2012;61(5):706-14.
140. Hron BM, Ebbeling CB, Feldman HA, Ludwig DS. Hepatic, adipocyte, enteric and pancreatic hormones: response to dietary macronutrient composition and relationship with metabolism. Nutr Metab (Lond). 2017;14:44
