Biomedical papers - Ahead of Print

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. X:X | 10.5507/bp.2018.016

Dietary sucrose regulates the expression of the Cd36 gene in hepatic tissue of rats with obesity and Non Alcoholic Fatty Liver Disease (NAFLD)

Rodolfo Quintana Castroa,b, Ida Soto Rodrigueza, Rosa A. Deschamps Lagoa, Peter Grube Pagolac, Jorge Rodriguez Antolind, Adriana Peres Quintala, Jaime Rivera Riveraa, Alfonso Alexander Aguileraa,b
a Facultad de Bioanalisis, Universidad Veracruzana, Carmen Serdán s/n. Col. Flores Magon, Veracruz, Ver., 91700. Mexico
b Escuela de Medicina, Universidad Cristobal Colon, Carr. Veracruz-Medellin s/n. Col. Puente Moreno, Boca del Rio, Ver., 94271. Mexico
c Instituto de Investigaciones Medico-Biologicas, Universidad Veracruzana, Carmen Serdan s/n. Col. Flores Maron, Veracruz, Ver., 91700. Mexico
d Centro Tlaxcala de Biologia de la Conducta, Universidad Autonoma de Tlaxcala, Carretera Tlaxcala-Puebla Km. 15., 90062. Mexico

Aim: To evaluate the mRNA expression levels of Cd36 in adipose and hepatic tissues, in rats with NAFLD after the consumption of sucrose for 10 and 20 weeks.

Methods: Twenty Wistar rats, all nearly 21 days old were divided into two experimental groups (NAFLD-10 and NAFLD-20), that received a standard diet (2014 Teklad Global) plus 30% sucrose in their drinking water for 10 and 20 weeks and the control groups (C Groups). Variables such as body weight, food intakes, and serum parameters were measured. Adipose and hepatic tissues were extirpated; some tissue was preserved in formalin and some at -70 °C until analysis. Histological analysis was carried out, and the Cd36 mRNA expression levels were determined.

Results: The rats in the NAFLD-10 and NAFLD-20 groups showed a significative increase in abdominal fat, triglycerides, free fatty acids, insulin, AST, ALT, uric acid and HOMA index; as well as changes in the cellular dynamics in adipose tissue, (adipocytes hypertrophic: >1500 µm2) with respect to the control groups (P<0.05). The histological analysis showed development of mild portal hepatitis in rats of the NAFLD-10 group and grade 1 hepatic steatosis with mild portal inflammation in rats of the NAFLD-20 group. Finally, Cd36 mRNA expression levels were significantly increased in hepatic tissue after 10 (1.5-fold) and 20 (3.5-fold) weeks of sucrose ingestion (P<0.05).

Conclusion: mRNA expression is a molecular mechanism involved in the development of NAFLD associated with obesity in rats consuming sucrose. However, there was increased Cd36 mRNA expression only in hepatic tissue while in hypertrophic adipose tissue mRNA levels remained unchanged.

Keywords: fatty liver, metabolic syndrome, sucrose, CD36, insulin resistance, obesity

Received: September 11, 2017; Accepted: April 4, 2018; Prepublished online: May 15, 2018


References

  1. Romeo GR, Lee J, Shoelson SE. Metabolic syndrome, insulin resistance, and roles of inflammation-mechanisms and therapeutic targets. Arterioscler Thromb Vasc Biol 2012;32:1771-6.
  2. Angulo P.Obesity and nonalcoholic fatty liver disease. Nutr Rev 2007;65:57-63.
  3. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, Vanni E, Villanova N, Melchionda N, Rizzeto M. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003;37:917-23.
  4. Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: From steatosis to cirrhosis. Hepatology 2006;43:S99-S112.
  5. Tacke F, Luedde T, Trautwein C.Inflammatory pathways in liver homeostasis and liver injury. Clin Rev Allergy Immunol 2009;36:4-12.
  6. Johnson L, Mander AP, Jones LR, Emmett PM, Jebb, SA. Is sugars-weetened beverage consumption associated with increased fatness in children? Nutrition 2007;23:557-63.
  7. Palmer JR, Boggs DA, Krishnan S, Hu FB, Singer M, Rosenberg L. Sugar-sweetened beverages and incidence of type 2 diabetes mellitus in African American women. Arch Intern Med 2008;168:1487-92.
  8. Segal, M.S., Gollub, E., Johnson, R.J. Is the fructose index more relevant with regards to cardiovascular disease than the glycemic index? Eur J Nutr 2007;46:406-17.
  9. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005;115:1343-51.
  10. Silverstein RL, Febbraio, M. CD36, a scavenger receptor involved in immunity, metabolism, angiogenesis, and behavior. Sci Signal 2009;2:re3.
  11. Pepino MY, Kuda O, Samovski D, Abumrad NA. Structure-function of CD36 and importance of fatty acid signal transduction in fat metabolism. Annu Rev Nutr 2014;34:281-303.
  12. Tran TT, Poirier H, Clement L, Nassir F, Pelsers MM,Petit V, Degrace P, Monnot MC, Glatz JF, Abumrad NA, Besnard P, Niot I. Luminal lipid regulates CD36 levels and downstream signaling to stimulate chylomicron synthesis. J Biol Chem 2011;286:25201-10.
  13. Nassir F, Adewole OL, Brunt EM, Abumrad NA. CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice. J Lipid Res 2013;54:2988-97.
  14. Berlanga A, Guiu-Jurado E, Porras JA, Auguet T. Molecular pathways in non-alcoholic fatty liver disease. Clin Exp Gastroenterol 2014;7:221-39.
  15. Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis. Hepatology 2010;52:1836-46.
  16. Garbacz WG, Lu P, Miller TM, Poloyac SM, Eyre NS, Mayrhofer G, Xu M, Ren S, Xie W. Hepatic overexpression of CD36 improves glycogen homeostasis and attenuates high-fat diet-induced hepatic steatosis and insulin resistance. Mol Cell Biol 2016;36(21):2715-27.
  17. SAGARPA. Norma Oficial Mexicana NOM-062-ZOO-1999, Especificaciones técnicas para la producción, cuidado y uso de los animales de laboratorio. Diario Oficial de la Federación. Fecha de publicación 22 de agosto de 2001.
  18. 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.
  19. Folch J, Lees M, Sloane Stanley G.H, A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957;226:497-509.
  20. Arias N, Macarulla MT, Aguirre L, MartÍnez-Castaño MG, Portillo MP. Quercetin can reduce insulin resistance without decreasing adipose tissue and skeletal muscle fat accumulation. Genes Nutr 2014;9:361.
  21. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999;94:2467-74.
  22. Johnson, RJ, Segal MS, Sautin Y, Nakagawa T, Feig DI, Kang DH, Gersch MS, Benner S, Sanchez-Lozada LG. Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am J Clin Nutr 2007;86:899-906.
  23. Aitman TJ, Glazier AM, Wallace CA, Cooper LD, Norsworthy PJ, Wahid FN, Al-Majali KM, Trembling PM, Mann CJ, Shoulders CC, Graf D, St Lezin E, Kurtz TW, Kren V, Pravenec M, Ibrahimi A, Abumrad NA, Stanton LW, Scott J. Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nat Genet 1999;21(1):76-83.
  24. Alexander AA, Angulo GO, Quintana CR, Ida Soto RI, Guadalupe Sánchez OMG, Rosa María Oliart RRM. CD36 gene expression induced by fish oil in abdominal adipose tissue of rats with metabolic syndrome. J Food Nutr Disord 2017;6(2):1-6
  25. Dhingra R, Sullivan L, Jacques PF, Wang TJ, Fox CS, Meigs JB, D'Agostino RB, Gaziano JM, Vasan RS. Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community. Circulation 2007;116:480-8.
  26. Nseir W, Nassar F, Assy N. Soft drinks consumption and nonalcoholic fatty liver disease. World J Gastroenterol 2010;16:2579-88.
  27. Desprees JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P. Larose E, Rodés Cabau J, Bertrand OF, Poirier P. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol 2008;28:1039-49.
  28. Tsuriya D, Morita H, Morioka T, Takahashi N, Ito T, Oki Y, Nakamura H. Significant correlation between visceral adiposity and high-sensitivity C-reative protein (hs-CRP) in Japanese subjects. Intern Med 2011;50:2767-73.
  29. Reyes M, Gahagan S, Díaz E, Blanco E, Leiva L, Lera L, Burrows R. Relationship of Adiposity and insulin Resistance Mediated by inflammation in a Group of Overweight and Obese Chilean Adolescents. Nutr J 2011;10:1-4.
  30. Jo J, Gavrilova O, Pack S, Jou W, Mullen S, Sumner AE, Cushman SW, Periwal V. Hypertrophy and/or hyperplasia: dynamics of adipose tissue growth. PLoS Comput Biol 2009;3:e1000324.
  31. Jo J, Guo J, Liu T, Mullen S, Hall KD, Cushman SW et al. Hypertrophy-Driven adipocyte death overwhelms recruitment under prolonged weight gain. Biophys J 2010;11:3535-44.
  32. Fang L, Guo F, Zhou L, Stahl R, Grams J. The cell size and distribution of adipocytes from subcutaneous and visceral fat is associated with type 2 diabetes mellitus in humans. Adipocyte 2015;4:273-9.
  33. Kursawe R, Eszinger M, Narayan D, Liu T, Bazuine M, Cali AMG, D'Adamo E, Shaw M, Pierpont B, Shulman GL, Cushman SW, Sherman A, Caprio S. Cellularity and adipogenic profile of the abdominal subcutaneous adipose tissue from obese adolescents: association with insulin resistance and hepatic steatosis. Diabetes 2010;9:2288-96.
  34. Lee YJ, Ko E H, Kim JE, Kim E, Lee H, Choi H, Yu JH, Kim HJ, Seong, JK, Kim KS, Kim JW. Nuclear receptor PPAR- regulated monoacylglycerol O-acyltransferase 1 (MGAT1) expression is responsible for the lipid accumulation in diet-induced hepatic steatosis. Proc Natl Acad Sci USA 2012;109:13656-61.
  35. Rahimian R, Masih-Khan E, Lo M, van Breemen C, McManus BM, Dubé GP. Hepatic overexpression of peroxisome proliferator activated receptor γ2 in the ob/ob mouse model of non-insulin dependent diabetes mellitus. Mol Cell Biochem 2001;224:29-37.
  36. Schadinger SE, Bucher NL, Schreiber BM and Farmer SR. Insulin Enhances Hepatic Expression of FA Translocase CD36 PPARγ2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes. Am J Physiol Endocrinol Metab 2005;288:E1195-E1205.
  37. Sheedfar F, Sung MM, Aparicio-Vergara M, Kloosterhuis NJ, Miquilena-Colina ME, Vargas-Castrillón J, Febbraio M, Jacobs RL, de Bruin A, Vinciguerra M, García-Monzón C, Hofker MH, Dyck JR, Koonen DP. Increased hepatic CD36 expression with age is associated with enhanced susceptibility to nonalcoholic fatty liver disease. Aging (Albany NY) 2014;6:281-95.
  38. Chang AM, Halter JB. Aging and insulin secretion. Am J Physiol Endocrinol Metab 2003;284:E7-12.
  39. Bonen A, Benton CR, Campbell SE, Chabowski A, Clarke DC, Han XX, Glatz JFC, Luiken JJFP. Plasmalemmal fatty acid transport is regulated in heart and skeletal muscle by contraction, insulin and leptin, and in obesity and diabetes. Acta Physiol Scand 2003;178:347-56.
  40. Coort SLM, Hasselbaink DM, Koonen DPY, Willems J, Coumans WA, Chabowski A, van der Vusse GJ, Bonen A, Glatz JFC, Luiken JJFP. Enhanced sarcolemmal FAT/CD36 content and triacylglycerol storage in cardiac myocytes from obese zucker rats. Diabetes 2004;53:1655-63.
  41. Schwenk RW, Luiken JJFP, Bonen A, Glatz JFC. Regulation of sarcolemmal glucose and fatty acid transporters in cardiac disease. Cardiovasc Res 2008;79:249-58.