Journal of Food and Nutrition Research
ISSN (Print): 2333-1119 ISSN (Online): 2333-1240 Website: Editor-in-chief: Prabhat Kumar Mandal
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Journal of Food and Nutrition Research. 2018, 6(12), 725-730
DOI: 10.12691/jfnr-6-12-2
Open AccessArticle

High Fiber Diet Suppression of TLR4 and NFκβ Gene Expression Correlated with TNF-α and IL-6 Levels in Hypertriglyceridemia Rats

I Gusti Ayu Nyoman Danuyanti1, 2, , Arta Farmawati3 and Sunarti3

1Doctoral Program, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia

2Departement of Medical Laboratory Technology, Politeknik Kesehatan Mataram, Mataram, Indonesia

3Department of Biochemistry, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia

Pub. Date: December 19, 2018

Cite this paper:
I Gusti Ayu Nyoman Danuyanti, Arta Farmawati and Sunarti. High Fiber Diet Suppression of TLR4 and NFκβ Gene Expression Correlated with TNF-α and IL-6 Levels in Hypertriglyceridemia Rats. Journal of Food and Nutrition Research. 2018; 6(12):725-730. doi: 10.12691/jfnr-6-12-2


Hypertriglyceridemia causes hypoxia and increases the release of free fatty acids in adipose tissue through lipolysis which stimulates an increase in TLR4 and NFκβ levels as well as TNF-α and IL-6 secretion. The high fiber diet had a suppressing effect against TLR4 and NFκβ gene expression and decreased TNF-α and IL-6 levels. This study evaluated the effect of high fiber diet (P1= 1.04 g content of fiber/rat/day, P2= 2.07 g content of fiber /rat/day and P3= 3.11 g content of fiber/rat/day) on TNF-α and IL-6 levels as well as expression of TLR4 and NFκβ in rats induced by high fat and fructose diet for 6 weeks. The findings indicate that the administration of high fiber diet to the hypertriglyceridemia rats could control body weight gain and significantly reduce TNF-α and IL-6 levels (p<0.05) lower than the hypertriglyceridemia groups when compared before treatment. In addition, the treatment of high fiber diet resulted in suppressing the expression of TLR4 and NFκβ gene (p<0.05) when compared with the normal and hypertriglyceridemia groups. The suppression of TLR4 and NFκβ were correlated with TNF-α and IL-6 levels. In conclusion, the administration of the high fiber diet to the hypertriglyceridemia rats was able to decrease TNF-α and IL-6 levels possibly by suppression of TLR4 and NFκB gene expression.

TLR4 NFκβ TNF-α IL-6 hypertriglyceridemia high fiber diet

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[1]  Coate, K.C., Scott, M., Farmer, B., et al., “Chronic consumption of a high-fat/high-fructose diet renders the liver incapable of net hepatic glucose uptake,” Am J Physiol Endocrinol Metab, 299(6). E887-E898. 2010.
[2]  Fernández-Sánchez, A., Madrigal-Santillán, E., Bautista, M., et al., “Inflammation, oxidative stress, and obesity,” Int. J. Mol. Sci, 12(5). 3117-3132. 2011.
[3]  Zhu, Y., Wang, C., Song, G., Zang, S., Liu, Y., Li, L., “Toll-like receptor-2 and-4 are associated with hyperlipidemia,” MoL Med Rep, 12(6). 8241-8246. 2015.
[4]  Stanhope, K.L., Havel, P.J., “Fructose consumption: potential mechanisms for its effects to increase visceral adiposity and induce dyslipidemia and insulin resistance,” Curr Opin Lipidol, 19(1). 1733S-1737S. 2008.
[5]  Tranchida, F., Tchiakpe, L., Rakotoniaina, Z., Deyris,V., Ravion O., Hiol, A., “Long-term high fructose and saturated fat diet affects plasma fatty acid profile in rats,” J Zhejiang Univ Sci B, 13(4). 307-317. 2012.
[6]  Bays, H.E., Toth, P.P., Kris-Etherton, P.M., et al., “Obesity, adiposity, and dyslipidemia: a consensus statement from the National Lipid Association,” J Clin Lipidol, 7(4). 304-383. 2013.
[7]  Mohamed, S., “Functional foods against metabolic syndrome (obesity, diabetes, hypertension and dyslipidemia) and cardiovasular disease,” Trends Food Sci Technol, xx(2013). 1-15. 2013.
[8]  Masi, L.N., Martins, A.R., Crisma, A.R., et al., “Combination of a high-fat diet with sweetened condensed milk exacerbates inflammation and insulin resistance induced by each separately in mice,” Sci. Rep, 7(3937). 1-10. 2017.
[9]  Glass, C.K., Olefsky, J.M., “Inflammation and lipid signaling in the etiology of insulin resistance”, Cell Metabolism, 15(5). 635-645. 2012.
[10]  Ventura, L.L.A., Fortes, N.C.L., Santiago, H.C., Caliari, M.V., Gomes, M.A., Oliveira, D.R., “Obesity-induced diet leads to weight gain, systemic metabolic alterations, adipose tissue inflammation, hepatic steatosis, and oxidative stress in gerbils (Meriones unguiculatus),” PeerJ, 5(e2967). 1-19. 2017.
[11]  Kanasaki, K., Taduri, G., Koya, D.. “Diabetic nephropathy: the role of inflammation in fibroblast activation and kidney fibrosis,” Front Endocrinol, 4(7). 1-15. 2013.
[12]  Li, J., Sapper, T.N., Mah, E., et al., “ScienceDirect Green tea extract treatment reduces NFκB activation in mice with diet-induced nonalcoholic steatohepatitis by lowering TNFR1 and TLR4 expression and ligand availability ☆ Reverse sequence,” JNB, 41. 34-41. 2017.
[13]  Schwartz, E.A., Zhang, W.Y., Karnik, S.K., et al., “Nutrient modification of the innate immune response: a novel mechanism by which saturated fatty acids greatly amplify monocyte inflammation,” Arterioscler Thromb Vasc Biol, 30(4). 802-808. 2010.
[14]  Al-Lahham, Peppelenbosch, M.P., Roelofsen, H., Vonk, R.J., Venema, K., “Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms,” Biochim.Biophys.Acta, 1801(11). 1175-1183. 2010.
[15]  Tedelind, S., Westberg, F., Kjerrulf, M., Vidal, A., “Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease,” World J Gastroenter, 13(20). 2826-2832. 2007.
[16]  Sunarti, Rubi, D.S., Sadewa, A.H., “The effect of pumpkin on GLP-1 and HOMA-β in hypercholesterolemic rats,” Rom J Diabetes Nutr Metab Dis, 23(1). 19-25. 2016.
[17]  Fushimi, T., Suruga, K., Oshima, Y., Fukiharu, M., Tsukamoto, Y., Goda, T., “Dietary acetic acid reduces serum cholesterol and triacylglycerols in rats fed a cholesterol-rich diet,” Br J Nutr, 95(5). 916-924. 2006.
[18]  Maryanto, S., Fatimah, S., Sugiri, S., Marsono, Y., “Efek Pemberian Buah Jambu Biji Merah terhadap Produksi Scfa dan Kolesterol dalam Caecum Tikus Hiperkolesterolemia,” Agritech, 33(3). 334-339. 2013.
[19]  Lee, S., Han, H.W., Yim, S.Y.,”Function cholesterol diet-induced alteration of gut,” Food Funct, 6(2). 492-500. 2015.
[20]  Van der Beek, C.M., Canfora, E.E., Lenaerts, K., et al., “Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men,” Clin Sci,130(22). 2073-2082. 2016.
[21]  Vieira, T., Galvão, I., Macia, L.M., et al.,”Dietary fiber and the short-chain fatty acid acetate promote resolution of neutrophilic inflammation in a model of gout in mice,” J Leukoc Biol, 101(1). 275-284. 2017.
[22]  El-sheikh, N., “Counteracting Methionine Choline-Deficient Diet-induced Fatty Liver by Administration of Turmeric and Silymarin,” J. Appl. Sci. Res, 7(12). 1812-1820. 2011.
[23]  Ble-Castillo, J.L., Aparicio-Trapala, M.A., Juárez-Rojo, I.E., et al., “Differential effects of high-carbohydrate and high-fat diet composition on metabolic control and insulin resistance in normal rats,” Int. J. Environ Res. Public Health, 9(5). 1663-1676. 2012.
[24]  Sasidharan, S.R., Joseph, J.A., Anandakumar, S., et al., “An experimental approach for selecting appropriate rodent diets for research studies on metabolic disorders,” BioMed research international, 2013. 1-9. 2013.
[25]  Ihedioha, J.I., Noel-Uneke, O.A., Ihedioha, T.E., “Reference values for the serum lipid profile of albino rats (Rattus norvegicus) of varied ages and sexes,” Comp Clin Pathol, 22(1). 93-99. 2013.
[26]  Livak, K.J., Schmittgen, T.D., “Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2ΔΔCt Method,” METHOD, 26. 402-408. 2001.
[27]  Slavin, J., “Fiber and prebiotics: mechanisms and health benefits,” Nutrients, 5(4). 1417-1435. 2013.
[28]  Dahl, W.J., Mialki, K.L., Eliasson, A.M., Mialki, K.L., “Olivera JD. Journal of the American College of Nutrition Health Benefits of Fiber Fermentation Health Benefits of Fiber Fermentation,” J Am Coll Nutr, 36(2). 127-136. 2017.
[29]  Besten, G.D., Eunen, K.V., Groen, A.K., et al., “The role of short-chain fatty acids in the interplay between diet, gut microbiota and host energy metabolism,” J. Lipid Res, 54. 2325-2340. 2013.
[30]  Adam, C.L., Williams, P.A., Garden, K.E., Thomson, L.M., Ross, A.W.,”Dose-Dependent Effects of a Soluble Dietary Fibre (Pectin) on Food Intake, Adiposity, Gut Hypertrophy and Gut Satiety Hormone Secretion in Rats,” PLoS ONE, 10(1). 1-14. 2015.
[31]  Cai, D., Yuan, M., Frantz, D.F., Melendez, P.A., et al., “Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB.” Nat. Med, 11. 183-190. 2005.