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http://dx.doi.org/10.3746/jkfn.2013.42.10.1576

Effects of Dietary Fructose and Glucose on Hepatic Steatosis and NLRP3 Inflammasome in a Rodent Model of Obesity and Type 2 Diabetes  

Lee, Hee Jae (Dept. of Food and Nutrition and Human Ecology Research Institute, Chonnam National University)
Yang, Soo Jin (Dept. of Food and Nutrition and Human Ecology Research Institute, Chonnam National University)
Publication Information
Journal of the Korean Society of Food Science and Nutrition / v.42, no.10, 2013 , pp. 1576-1584 More about this Journal
Abstract
This study is carried out to assess the relative effects of different doses of dietary glucose or fructose on non-alcoholic fatty liver disease (NAFLD) and hepatic metaflammation in a rodent model of type 2 diabetes. KK/HlJ male mice were fed experimental diets as follows: 1) control (CON), 2) moderate glucose (MG, 30% of total calories as glucose), 3) high glucose (HG, 60% of total calories as glucose), 4) moderate fructose (MF, 30% of total calories as fructose), and 5) high fructose (HF, 60% of total calories as fructose) for three weeks. Food intake was not affected by treatments. Compared with HF, HG not only increased serum fasting glucose and area under the curve during oral glucose tolerance test, but also decreased the levels of serum insulin and adiponectin. It indicated that glucose control was complicated via high glucose intake. High fructose treatment led to increased triglyceride in the serum and liver. In comparison to HG, high fructose diet activated NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome consisting of apoptosis-associated speck-like protein containing a CARD (ASC), NLRP3 and caspase 1, which increases interleukin (IL)-$1{\beta}$ maturation and secretion. The activation of NLRP3 inflammasome was accompanied by increased levels of tumor necrosis factor alpha (TNF-${\alpha}$) and IL-6. However, the expression of NLRP3 inflammasome components and pro-inflammatory cytokines did not differ between CON and HG. These data suggested that dietary fructose triggers hepatic metaflammation accompanied by NLRP3 inflammasome activation and has deleterious effects on NAFLD.
Keywords
dietary sugar; fructose; hepatic metaflammation; NLRP3 inflammasome; non-alcoholic fatty liver disease;
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1 Aller EEJG, Abete I, Astrup A, Martinez JA, van Baak MA. 2011. Starches, sugars and obesity. Nutrients 3: 341-369.   DOI
2 Malik VS, Popkin BM, Bray GA, Despres JP, Willett WC, Hu FB. 2010. Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a meta-analysis. Diabe tes care 33: 2477-2483.   DOI   ScienceOn
3 Basaranoglu M, Basaranoglu G, Sabuncu T, Senturk H. 2013. Fructose as a key player in the development of fatty liver disease. World J Gastroenterol 19: 1166-1172.   DOI   ScienceOn
4 Dhingra R, Sullivan L, Jacques PF, Wang TJ, Fox CS, Meigs JB, D'Agostino RB, Gaziano JM, Vasan RS. 2007. Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community. Circulation 116: 480-488.   DOI   ScienceOn
5 Yoshida M, McKeown NM, Rogers G, Meigs JB, Saltzman E, D'Agostino R, Jacques PF. 2007. Surrogate markers of insulin resistance are associated with consumption of sugar-sweetened drinks and fruit juice in middle and older-aged adults. J Nutr 137: 2121-2127.   DOI
6 Ludwig DS, Peterson KE, Gortmaker SL. 2001. Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis. Lancet 357: 505-508.   DOI   ScienceOn
7 Bray GA. 2010. Soft drink consumption and obesity: it is all about fructose. Curr Opin Lipidol 21: 51-57.   DOI   ScienceOn
8 Nseir W, Nassar F, Assy N. 2010. Soft drinks consumption and nonalcoholic fatty liver disease. World J Gastroentero 16: 2579-2588.   DOI
9 Abid A, Taha O, Nseir W, Farah R, Grosovski M, Assy N. 2009. Soft drink consumption is associated with fatty liver disease independent of metabolic syndrome. J Hepatol 51: 918-924.   DOI   ScienceOn
10 Ouyang X, Cirillo P, Sautin Y, McCall S, Bruchette JL, Diehl AM, Johnson RJ, Abdelmalek MF. 2008. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol 48: 993-999.   DOI   ScienceOn
11 Abdelmalek MF, Suzuki A, Guy C, Unalp-Arida A, Colvin R, Johnson RJ, Diehl AM. 2010. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology 51: 1961-1971.   DOI   ScienceOn
12 Stanhope KL, Schwarz JM, Keim NL, Griffen SC, Bremer AA, Graham JL, Hatcher B, Cox CL, Dyachenko A, Zhang W, McGahan JP, Seibert A, Krauss RM, Chiu S, Schaefer EJ, Ai M, Otokozawa S, Nakajima K, Nakano T, Beysen C, Hellerstein MK, Berglund L, Havel PJ. 2009. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest 119: 1322-1334.   DOI   ScienceOn
13 Vos MB, Lavine JE. 2013. Dietary fructose in nonalcoholic fatty liver disease. Hepatology 57: 2525-2531.   DOI   ScienceOn
14 Almeda-Valdes P, Cuevas-Ramos D, Aguilar-Salinas CA. 2009. Metabolic syndrome and non-alcoholic fatty liver disease. Ann Hepatol 8: S18-S24.
15 Day CP, James OF. 1998. Steatohepatitis: a tale of two "hits"? Gastroenterology 114: 842-845.   DOI   ScienceOn
16 Mellor KM, Bell JR, Young MJ, Ritchie RH, Delbridge LM. 2011. Myocardial autophagy activation and suppressed survival signaling is associated with insulin resistance in fructose-fed mice. J Mol Cell Cardiol 50: 1035-1043.   DOI   ScienceOn
17 Browning JD, Baker JA, Rogers T, Davis J, Satapati S, Burgess SC. 2011. Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. Am J Clin Nutr 93: 1048-1052.   DOI
18 Page KA, Chan O, Arora J, Belfort-Deaguiar R, Dzuira J, Roehmholdt B, Cline GW, Naik S, Sinha R, Constable RT, Sherwin RS. 2013. Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways. JAMA 309: 63-70.   DOI   ScienceOn
19 Sievenpiper JL, de Souza RJ, Mirrahimi A, Yu ME, Carleton AJ, Beyene J, Chiavaroli L, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Kendall CW, Jenkins DJ. 2012. Effect of fructose on body weight in controlled feeding trials: a systematic review and meta-analysis. Ann Intern Med 156: 291-304.   DOI   ScienceOn
20 Rippe JM, Angelopoulos TJ. 2013. Sucrose, high-fructose corn syrup, and fructose, their metabolism and potential health effects: what do we really know? Adv Nutr 4: 236-245.   DOI   ScienceOn
21 Sclafani A, Ackroff K. 2012. Flavor preferences conditioned by intragastric glucose but not fructose or galactose in C57BL/6J mice. Physiol Behav 106: 457-461.   DOI   ScienceOn
22 Foster-Powell K, Miller JB. 1995. International tables of glycemic index. Am J Clin Nutr 62: 871S-890S.   DOI
23 Tappy L, Le KA. 2010. Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev 90: 23-46.   DOI   ScienceOn
24 Cusi K. 2009. Nonalcoholic fatty liver disease in type 2 diabetes mellitus. Curr Opin Endocrinol Diabetes Obes 16: 141-149.   DOI
25 Thorburn AW, Crapo PA, Griver K, Wallace P, Henry RR. 1990. Long-term effects of dietary fructose on carbohydrate metabolism in non-insulin-dependent diabetes mellitus. Metabolism 39: 58-63.   DOI   ScienceOn
26 Ackerman Z, Oron-Herman M, Grozovski M, Rosenthal T, Pappo O, Link G, Sela BA. 2005. Fructose-induced fatty liver disease: hepatic effects of blood pressure and plasma triglyceride reduction. Hypertension 45: 1012-1018.   DOI   ScienceOn
27 Matsuzaka T, Shimano H, Yahagi N, Amemiya-Kudo M, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Tomita S, Sekiya M, Hasty A, Nakagawa Y, Sone H, Toyoshima H, Ishibashi S, Osuga J, Yamada N. 2004. Insulin-independent induction of sterol regulatory element-binding protein-1c expression in the livers of streptozotocin-treated mice. Diabetes 53: 560-569.   DOI   ScienceOn
28 Bantle JP, Raatz SK, Thomas W, Georgopoulos A. 2000. Effects of dietary fructose on plasma lipids in healthy subjects. Am J Clin Nutr 72: 1128-1134.   DOI
29 Maersk M, Belza A, Stodkilde-Jorgensen H, Ringgaard S, Chabanova E, Thomsen H, Pedersen SB, Astrup A, Richelsen B. 2012. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Am J Clin Nutr 95: 283-289.   DOI   ScienceOn
30 Teff KL, Grudziak J, Townsend RR, Dunn TN, Grant RW, Adams SH, Keim NL, Cummings BP, Stanhope KL, Havel PJ. 2009. Endocrine and metabolic effects of consuming fructose- and glucose-sweetened beverages with meals in obese men and women: influence of insulin resistance on plasma triglyceride responses. J Clin Endocrinol Metab 94: 1562-1569.   DOI   ScienceOn
31 Spruss A, Kanuri G, Wagnerberger S, Haub S, Bischoff SC, Bergheim I. 2009. Toll-like receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice. Hepatology 50: 1094-1104.   DOI   ScienceOn
32 Haub S, Kanuri G, Volynets V, Brune T, Bischoff SC, Bergheim I. 2010. Serotonin reuptake transporter (SERT) plays a critical role in the onset of fructose-induced hepatic steatosis in mice. Am J Physiol Gastrointest Liver Physiol 298: G335-344.   DOI
33 Tilg H. 2010. The role of cytokines in non-alcoholic fatty liver disease. Dig Dis 28: 179-185.   DOI   ScienceOn
34 Crespo J, Cayon A, Fernandez-Gil P, Hernandez-Guerra M, Mayorga M, Dominguez-Diez A, Fernandez-Escalante JC, Pons-Romero F. 2001. Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology 34: 1158-1163.   DOI   ScienceOn
35 Banks AS, Kon N, Knight C, Matsumoto M, Gutierrez-Juarez R, Rossetti L, Gu W, Accili D. 2008. SirT1 gain of function increases energy efficiency and prevents diabetes in mice. Cell Metab 8: 333-341.   DOI   ScienceOn
36 Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. 1997. Protection from obesity-induced insulin resistance in mice lacking TNF-${\alpha}$ function. Nature 389: 610-614.   DOI   ScienceOn
37 Tilg H, Moschen AR. 2008. Inflammatory mechanisms in the regulation of insulin resistance. Mol Med 14: 222-231.
38 Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X. 2009. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab 9: 327-338.   DOI   ScienceOn
39 Pfluger PT, Herranz D, Velasco-Miguel S, Serrano M, Tschop MH. 2008. Sirt1 protects against high-fat diet-induced metabolic damage. Proc Natl Acad Sci U S A 105: 9793-9798.   DOI   ScienceOn
40 Duffey KJ, Popkin BM. 2007. Shifts in patterns and consumption of beverages between 1965 and 2002. Obesity (Silver Spring) 15: 2739-2747.   DOI   ScienceOn
41 Bray GA. 2013. Energy and fructose from beverages sweetened with sugar or high-fructose corn syrup pose a health risk for some people. Adv Nutr 4: 220-225.   DOI   ScienceOn
42 Marriott BP, Olsho L, Hadden L, Connor P. 2010. Intake of added sugars and selected nutrients in the United States, National Health and Nutrition Examination Survey (NHANES) 2003-2006. Crit Rev Food Sci Nutr 50: 228-258.   DOI   ScienceOn
43 KNS. 2010. Dietary reference intakes for Koreans. The Korean Nutrition Society, Korea. p 65.