Nutritional Effects and Biochemical Mechanisms in Non-alcoholic Fatty Liver Disease
DOI:
https://doi.org/10.47320/rasbran.2021.1436Abstract
The Non-alcoholic Fatty Liver Disease (NAFLD) has gained alarming proportions, affecting about 25-30% of the world's population. The occurrence of NAFLD is associated with overweight, insulin resistance, and metabolic syndrome. It is a silent disease that evolves from an initial fat liver accumulation to the steatosis, hepatitis, fibrosis, cirrhosis, and carcinoma. Morbimortality associated with NAFLD has increased significantly, along with the growth of overweight in the population. There is still neither a specific marker for the diagnosis nor a pharmacological treatment for the disease. Therefore, both the prevention and treatment are based on a change in lifestyle, with the adoption of healthy eating habits that must lead to weight loss, improving the health condition. The objective of this review was to search and synthesize updated scientific information about the DHGNA. The search was directed to dietary influences in the development, prevention, and treatment of NAFLD and to the biochemical and metabolic mechanisms involved with the disease. By doing that we could provide information to help understanding the DHGNA's diet and biochemistry, as well as the importance of the disease on the light of public health. The issues reported help to enhance the nutritionist in the current scenario of food and nutrition education, aimed at the prevention and treatment of the NAFLD.
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Byass P. The global burden of liver disease: a challenge for methods and for public health. BMC Med. 2014;12:159. DOI: https://doi.org/10.1186/s12916-014-0159-5
Oliveira CPMS, Mazo DFC. Hepatologia/Gastroenterologia - Doença hepática gordurosa não alcoólica: fisiopatogenia e relação com a terapêutica. In: Parise ER, Mendonça Filho HTF. Esteatose hepática: visão hepatológica e cardiometabólica. 1. ed. São Paulo: MTS Editora Arte de Cuidar; 2013.
Sayiner M, Koenig A, Henry L, Younossi ZM. Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in the United States and the rest of the world. Clin Liver Dis. 2016;20(2):205-14. DOI: https://doi.org/10.1016/j.cld.2015.10.001
Bellentani S. The epidemiology of non-alcoholic fatty liver disease. Liver Int. 2017;37(1):81-4. DOI: https://doi.org/10.1111/liv.13299
Hardy T, Oakley F, Anstee QM, Day CP. Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum. Annu Rev Pathol: Mechanisms of Disease. 2016;11:451-96. DOI: https://doi.org/10.1146/annurev-pathol-012615-044224
Parise ER, Santos VN. Hepatologia/Gastroenterologia. Esteatose: definição, epidemiologia e diagnóstico. In: Parise ER, Mendonça Filho HTF. Esteatose hepática: visão hepatológica e cardiometabólica. 1. ed. São Paulo: MTS Editora Arte de Cuidar; 2013.
Parise ER, Mendonça Filho HTF. Esteatose hepática: visão hepatológica e cardiometabólica. 1. ed. São Paulo: MTS Editora Arte de Cuidar; 2013.
Ertle J, Dechêne A, Sowa JP, Penndorf V, Herzer K, Kaiser G, Schlaak JF, Gerken G, Syn WK, Canbay A. Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. Int J Cancer. 2011;128(10):2436-43. DOI: https://doi.org/10.1002/ijc.25797
Pockros PJ, Bisceglie AMD, Bloom A. Direct-acting antivirals for the treatment of hepatitis C virus infection. [Internet]. UpToDate. [acesso em 5 out 2018] Disponível em: https://www.uptodate.com/contents/direct-acting-antivirals-for-the-treatment-of-hepatitis-c-virus-infection/print.
Younossi Z, Stepanova M, ONG JP, Jacobson IM, Bugianesi E, Duseja A, Eguchi Y, Wong VW, Negro F, Yilmaz Y, Romero-Gomez M, George J, Ahmed A, Wong R, Younossi I, Ziayee M, Afendy A. Global nonalcoholic steatohepatitis council. Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates. Clin Gastroenterol Hepatol. 2018;18:30611-6.
Bertot LC, Adams LA. The natural course of non-alcoholic fatty liver disease. Int J Mol Sci. 2016;17(5):774. DOI: https://doi.org/10.3390/ijms17050774
Asselah T, Boyer N, Guimont MC, Cazals-Hatem D, Tubach F, Nahon K, Daïkha H, Vidaud D, Martinot M, Vidaud M, Degott C, Valla D, Marcellin P. Liver fibrosis is not associated with steatosis but with necroinflammation in French patients with chronic hepatitis C. Gut. 2003; 52:1638-43. DOI: https://doi.org/10.1136/gut.52.11.1638
Neuman MG, Schmilovitz-Weiss H, Hilzenrat N, Bourliere M, Marcellin P, Trepo C, Mazulli T, Moussa G, Patel A, Baig AA, Cohen L. Markers of inflammation and fibrosis in alcoholic hepatitis and viral hepatitis C. Int J Hepatology. 2012;2012:231210. DOI: https://doi.org/10.1155/2012/231210
Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, Washington MK, Germanidis G, Flaherty JF, Aguilar Schall R, Bornstein JD, Kitrinos KM, Subramanian GM, Mchutchison JG, Heathcote EJ. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381(9865):468-75. DOI: https://doi.org/10.1016/S0140-6736(12)61425-1
Marcellin P, Kutala BK. Liver diseases: a major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int. 2018;38(1):2-6. DOI: https://doi.org/10.1111/liv.13682
Dyson JK, Anstee QM, Mcpherson S. Non-alcoholic fatty liver disease: a practical approach to diagnosis and staging. Frontline Gastroenterol. 2014;5:211-218. DOI: https://doi.org/10.1136/flgastro-2013-100403
Dongiovanni P, Lanti C, Riso P, Valenti L. Nutritional therapy for nonalcoholic fatty liver disease. J Nutr Biochem. 2016;29:1-11. DOI: https://doi.org/10.1016/j.jnutbio.2015.08.024
Biblioteca virtual em saúde. [Internet]. Descritores em ciências da saúde. [acesso em 13 set 2018]. Disponível em: http://decs.bvs.br.
Amaya-Farfan J. Aflatoxin B1-induced hepatic steatosis: role of carbonyl compounds and active diols on steatogenesis. Lancet. 1999; 353(9154):747-8. DOI: https://doi.org/10.1016/S0140-6736(98)09261-7
Sociedade brasileira de hepatologia. [Internet]. Doença hepática gordurosa não alcoólica. [acesso em 3 out 2018]. Disponível em: http://www.sbhepatologia.org.br/pdf/Consenso_DHGNA_da_SBH-2015.pdf.
Miele L, Liguori A, Marrone G, Biolato M, Araneo C, Vaccaro FG, Gasbarrini A, Grieco A. Fatty liver and drugs: the two sides of the same coin. Eur Rev Med Pharmacol Sci. 2017;21(1):86-94.
Kumar R, Mohan S. Non-alcoholic fatty liver disease in lean subjects: characteristics and implications. J Clin Transl Hepatol. 2017;5(3):216-23. DOI: https://doi.org/10.14218/JCTH.2016.00068
Curi R, Pompéia C, Miyasaka CK, Procopio J. Entendendo a gordura: os ácidos graxos. 1a ed. Barueri - SP: Editora Manole; 2002.
Manuais MSD. [Internet]. Versão saúde para a família. [acesso em out 2018]. Disponível em: https://www.msdmanuals.com/pt-br/casa/doenças-hepáticas-e-da-ves%C3%ADcula-biliar/fibrose-e-cirrose-do-f%C3%ADgado/fibrose-do-f%C3%ADgado.
Parise ER. Métodos de imagem e testes não invasivos no diagnóstico da DHGNA. Doença hepática gordurosa não alcoólica. [Internet]. Sociedade brasileira de hepatologia. [acesso em 3 out 2018]. Disponível em: http://www.sbhepatologia.org.br/pdf/revista_monotematico_hepato.pdf.
BRASIL. Ministério da Saúde. [Internet]. Elastografia hepática ultrassônica no diagnóstico da fibrose hepática. Comissão nacional de incorporação de tecnologias no SUS. [acesso em 3 out 2018]. Disponível em: http://conitec.gov.br/images/Relatorios/2015/Elastografia_final.pdf.
Nelson DL, Cox MM. Regulação hormonal e integração do metabolismo em mamíferos. In: Princípios e Bioquímica de Lehninger. 6. ed. Porto Alegre - RS: Artmed; 2014.
Ipsen DH, Lykkesfeldt J, Tveden-Nyborg P. Molecular mechanisms of hepatic lipid accumulation in non‐alcoholic fatty liver disease. Cell Mol Life Sci. 2018;75:3313-27. DOI: https://doi.org/10.1007/s00018-018-2860-6
Bechmann LS, Hannivoort RA, Gerken G, Hotamisligil GS, Trauner M, Canbay A. The interaction of hepatic lipid and glucose metabolism in liver diseases. J Hepatol. 2012;56:952-64. DOI: https://doi.org/10.1016/j.jhep.2011.08.025
Projeto diretrizes [Internet]. Associação médica brasileira e conselho federal de medicina. Terapia nutricional nas doenças hepáticas crônicas e insuficiência hepática. [acesso em 3 out 2018]. Disponível em: https://diretrizes.amb.org.br/_BibliotecaAntiga/terapia_nutricional_nas_doencas_hepaticas_cronicas_e_insuficiencia_hepatica.pdf.
Kawano Y, Cohen DE. Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease. J Gastroenterol. 2013;48(8):434-41. DOI: https://doi.org/10.1007/s00535-013-0758-5
Zámbó V, Simon-Szabó L, Szelényi P, Kereszturi E, Bánhegyi G, Csala M. Lipotoxicity in the liver. World J Hepatol. 2013;5(10):550-7. DOI: https://doi.org/10.4254/wjh.v5.i10.550
Weijers RNM. Membrane flexibility, free fatty acids, and the onset of vascular and neurological lesions in type 2 diabetes. J Diabetes Metab Disord. 2016;15(13). DOI: https://doi.org/10.1186/s40200-016-0235-9
Sobrecases H, Lê KA, Bortolotti M, Schneiter P, Ith M, Kreis R, Boesch C, Tappy L. Effects of short-term overfeeding with fructose, fat and fructose plus fat on plasma and hepatic lipids in healthy men. Diabetes Metab. 2010;36(3):244-6. DOI: https://doi.org/10.1016/j.diabet.2010.03.003
Jensen T, Abdelmalek MF, Sullivan S, Nadeau KJ, Green M, Roncal C, Nakagawa T, Kuwabara M, Sato Y, Kang DH, Tolan DR, Sanchez-Lozada LG, Rosen HR, Lanaspa MA, Diehl AM, Johnson RJ. Fructose and Sugar: A Major Mediator of Nonalcoholic Fatty Liver Disease. J Hepatol. 2018;68(5):1063-75. DOI: https://doi.org/10.1016/j.jhep.2018.01.019
Cuppari L. Nutrição clínica no adulto. 4a ed. Barueri - SP: Editora Manole; 2019.
Samuel VT. Fructose induced lipogenesis: from sugar to fat to insulin resistance. Trends Endocronol Metab. 2011;22(2):60-5. DOI: https://doi.org/10.1016/j.tem.2010.10.003
Masarone M, Rosato V, Dallio M, Gravina AG, Aglitti A, Loguercio C, Federico A, Persico M. Role of Oxidative Stress in Pathophysiology of Nonalcoholic Fatty Liver Disease. Oxid Med Cell Longev. 2018;2018:1-14. DOI: https://doi.org/10.1155/2018/9547613
Bergamini CM, Gambetti S, Dondi A, Cervellati C. Oxygen, reactive oxygen species and tissue damage. Curr Pharm Des. 2004;10(14): 1611-26. DOI: https://doi.org/10.2174/1381612043384664
Stark G. Functional consequences of oxidative membrane damage. J Membr Biol. 2005;205(1):1-16. DOI: https://doi.org/10.1007/s00232-005-0753-8
Indo HP, Yen HC, Nakanishi I, Matsumoto K, Tamura M, Nagano Y, Matsui H, Gusev O, Cornette R, Okuda T, Minamiyama Y, Ichikawa H, Suenaga S, Oki M, Sato T, Ozawa T, Clair DK, Majima HJ. A mitochondrial superoxide theory for oxidative stress diseases and aging. J Clin Biochem Nutr. 2015;56(1):1-7. DOI: https://doi.org/10.3164/jcbn.14-42
Ota T, Gayet C, Ginsberg HN. Inhibition of apolipoprotein B100 secretion by lipid-induced hepatic endoplasmic reticulum stress in rodents. J Clin Invest. 2008;118:316-32. DOI: https://doi.org/10.1172/JCI32752
Zhang XQ, Xu CF, Yu CH, Chen WX, Li YM. Role of endoplasmic reticulum stress in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20:1768-76. DOI: https://doi.org/10.3748/wjg.v20.i7.1768
Sanyal AJ, Chalasani N, Kowdley KV, Mccullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675-85. DOI: https://doi.org/10.1056/NEJMoa0907929
Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, Chalasani N, Dasarathy S, Diehl AM, Hameed B, Kowdley KV, Mccullough A, Terrault N, Clark JM, Tonascia J, Brunt EM, Kleiner DE, Doo E. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385:956-65. DOI: https://doi.org/10.1016/S0140-6736(14)61933-4
Middleton KR, Anton SD, Perri MG. Long-term adherence to health behavior change. Am J Lifestyle Med. 2013;7:395-404. DOI: https://doi.org/10.1177/1559827613488867
Galizzi Filho J. Mudanças no estilo de vida. Doença hepática gordurosa não alcoólica [Internet]. Sociedade brasileira de hepatologia. [acesso em 3 out 2018]. Disponível em: http://www.sbhepatologia.org.br/pdf/revista_monotematico_hepato.pdf.
Help Guide. [Internet]. Emotional eating. How to recognize and stop emotional and stress eating. [acesso em 11 mai 2019]. Disponível em: https://www.helpguide.org/articles/diets/emotional-eating.htm/.
Muñoz VR, Gaspar RC, Kuga GK, Nakandakari SCBR, Baptista IL, Mekary RA, da Silva ASR, de Moura LP, Ropelle ER, Cintra DE, Pauli JR. Exercise decreases CLK2 in the liver of obese mice and prevents hepatic fat accumulation. J Cell Biochem. 2018;119(7):5885-5892. DOI: https://doi.org/10.1002/jcb.26780
Pereira RM, Rodrigues KCDC, Anaruma CP, Sant'Ana MR, de Campos TDP, Gaspar RS, Canciglieri RDS, de Melo DG, Mekary RA, da Silva ASR, Cintra DE, Ropelle ER, Pauli JR, de Moura LP. Short-term strength training reduces gluconeogenesis and NAFLD in obese mice. J Endocrinol. 2019;241(1):59-70. DOI: https://doi.org/10.1530/JOE-18-0567
Da Rocha AL, Pinto AP, Teixeira GR, Pereira BC, Oliveira LC, Silva AC, Morais GP, Cintra DE, Pauli JR, da Silva ASR. Exhaustive Training Leads to Hepatic Fat Accumulation. J Cell Physiol. 2017;232(8):2094-2103. DOI: https://doi.org/10.1002/jcp.25625
Kneeman JM, Misdraji J, Corey KE. Secondary causes of nonalcoholic fatty liver disease. Therap Adv Gastroenterol. 2012;5(3):199-207. DOI: https://doi.org/10.1177/1756283X11430859
Hospital Albert Einstein. Esteatose hepática. [Internet]. Guia de doenças e sintomas. [acesso em 3 out 2018]. Disponível em: https://www.einstein.br/Pages/Doenca.aspx?eid=251.
Marchesini G, Mazzotti A. NAFLD incidence and remission: only a matter of weight gain and weight loss? J Hepatol. 2015;62(1):15-7. DOI: https://doi.org/10.1016/j.jhep.2014.10.023
Marchesini G, Petta S, Dalle Grave R. Diet, weight loss, and liver health in nonalcoholic fatty liver disease: Pathophysiology, evidence, and practice. Hepatology. 2016;63(6):2032-43. DOI: https://doi.org/10.1002/hep.28392
Green CJ, Hodson L. The influence of dietary fat on liver fat accumulation. Nutrients. 2014;6(11):5018-33. DOI: https://doi.org/10.3390/nu6115018
Machado RM, Stefano JT, Oliveira CP, Mello ES, Ferreira FD, Nunes VS, De lima VM, Quintão EC, Catanozi S, Nakandakare ER, Lottenberg AM. Intake of trans fatty acids causes nonalcoholic steatohepatitis and reduces adipose tissue fat content. J Nutr. 2010;140(6):1127-32. DOI: https://doi.org/10.3945/jn.109.117937
Dhibi M, Brahmi F, Mnari A, Houas Z, Chargui I, Bchir L, Gazzah N, Alsaif MA, Hammami M. The intake of high fat diet with different trans fatty acid levels differentially induces oxidative stress and non alcoholic fatty liver disease (NAFLD) in rats. Nutr Metab. 2011;8(1):65. DOI: https://doi.org/10.1186/1743-7075-8-65
Rosqvist F, Iggman D, Kullberg J, Cedernaes J, Johansson HE, Larsson A, Johansson L, Ahlström H, Arner P, Dahlman I, Risérus U. Overfeeding polyunsaturated and saturated fat causes distinct effects on liver and visceral fat accumulation in humans. Diabetes. 2014;63(7):2356-68. DOI: https://doi.org/10.2337/db13-1622
Escribá PV. Membrane-lipid therapy: A historical perspective of membrane-targetedtherapies - From lipid bilayer structure to the pathophysiologicalregulation of cells. Biochim Biophys Acta Biomembr. 2017;1859(9):1493-506. DOI: https://doi.org/10.1016/j.bbamem.2017.05.017
Shen Y, Zhao Z, Zhang L, Shi L, Shahriar S, Chan RB, Di Paolo G, Min W. Metabolic activity induces membrane phase separation in endoplasmic reticulum. Proc Natl Acad Sci USA. 2017;114(51):13394-99. DOI: https://doi.org/10.1073/pnas.1712555114
George ES, Forsyth A, Itsiopoulos C, Nicoll AJ, Ryan M, Sood S, Roberts SK, Tierney AC. Practical Dietary Recommendations for the Prevention and Management of Nonalcoholic Fatty Liver Disease in Adults. Adv Nutr. 2018;9(1):30-40. DOI: https://doi.org/10.1093/advances/nmx007
Pereira RM, Botezelli JD, da Cruz Rodrigues KC, Mekary RA, Cintra DE, Pauli JR, da Silva ASR, Ropelle ER, de Moura LP. Fructose Consumption in the Development of Obesity and the Effects of Different Protocols of Physical Exercise on the Hepatic Metabolism. Nutrients. 2017 Apr 20;9(4):405. DOI: https://doi.org/10.3390/nu9040405
Parry SA, Hodson L. Influence of dietary macronutrients on liver fat accumulation and metabolismo. J Investig Med. 2017;65(8):1102-15. DOI: https://doi.org/10.1136/jim-2017-000524
Wehmeyer MH, Zyriax BC, Jagemann B, Roth E, Windler E, Schulze Zur Wiesch J, Lohse AW, Kluwe J. Nonalcoholic fatty liver disease is associated with excessive calorie intake rather than a distinctive dietary pattern. Medicine (Baltimore). 2016;95(23):e3887. DOI: https://doi.org/10.1097/MD.0000000000003887
Haufe S, Engeli S, Kast P, Böhnke J, Utz W, Haas V, Hermsdorf M, Mähler A, Wiesner S, Birkenfeld AL, Sell H, Otto C, Mehling H, Luft FC, Eckel J, Schulz-Menger J, Boschmann M, Jordan J. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects. Hepatology. 2011;53(5):1504-14. DOI: https://doi.org/10.1002/hep.24242
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