Modified High-Fat High-Sucrose Diet Promotes Obesity and Alters Colonic Cytokines

Bernadette Dian Novita, I Gede Putu Adhi Wedharga, Yudy Tjahjono, Hendy Wijaya, Imelda Theodora, Martha Ervina, Yufita Ratnasari Wilianto, Sianty Dewi, Irene Lingkan Parengkuan, Herjunianto Herjunianto, Sabrina Maria Ghasani, Michael Christian Limantoro, Ferdinand Wiliam Jaya

Abstract


BACKGROUND: Western dietary patterns are often associated with increasing non-communicable diseases, including inflammatory bowel disease (IBD). In experimental models, a high-fat high-sucrose (HFHS) diet is used to mimic metabolic and inflammatory effects of such diets, however the data regarding colonic inflammation in Indonesia remain limited. Therefore, this study was conducted evaluated the impact of HFHS feeding on colonic interleukin (IL)-6, IL-10 expression, and the IL-6/IL-10 ratio.

METHODS: Six weeks old male C57BL/6 mice were randomly assigned to a normal fat diet (NFD) or HFHS diet group and fed ad libitum for 8 weeks. Colonic tissues were collected, and IL-6 and IL-10 expression was analyzed by immunohistochemistry.

RESULTS: HFHS-fed mice showed significant increases in body weight (increased by 22.44%, p=0.0047) and caloric intake (increased by 125.17%, p=0.0000), confirming obesity induction. Colitis was also evident, with higher histological colitis scores (p=0.0072). However, colonic IL-6 (increased by 9.12%, p=0.1236), IL-10 (increased by 1.49%, p=0.8013), and the IL-6/IL-10 ratio (increased by 7.38%, p=0.4000) showed no significant differences compared to NFD.

CONCLUSION: In C57BL/6 mice, an 8-week modified HFHS diet induced obesity, increased caloric intake, and mucosal injury, but did not significantly alter colonic IL-6, IL-10, or their ratio. This suggests preserved mucosal immune homeostasis consistent with an early compensatory phase rather than overt cytokine-driven inflammation. Longer or more intensive exposure may disrupt this balance, highlighting the need for further studies to define the temporal threshold and clarify immune microbiome interactions in colitis progression.

KEYWORDS: high-fat high-sucrose diet, colon inflammation, IL-6, IL-10, obesity mice


Full Text:

PDF

References


Wang R, Li Z, Liu S, Zhang D. Global, regional and national burden of inflammatory bowel disease in 204 countries and territories from 1990 to 2019: A systematic analysis based on the Global Burden of Disease Study 2019. BMJ Open. 2023; 13: e065186, CrossRef.

Qiao J, Lin X, Wu Y, Huang X, Pan X, Xu J, et al. Global burden of non-communicable diseases attributable to dietary risks in 1990-2019. J Hum Nutr Diet. 2022; 35(1): 202-13, CrossRef.

Singh S, Dulai PS, Zarrinpar A, Ramamoorthy S, Sandborn WJ. Obesity in IBD: Epidemiology, pathogenesis, disease course and treatment outcomes. Nat Rev Gastroenterol Hepatol. 2017; 14(2): 110-21, CrossRef.

Rydell-Törmänen K, Johnson JR. The applicability of mouse models to the study of human disease. Methods Mol Biol. 2019; 1940: 3-22, CrossRef.

Martins T, Castro-Ribeiro C, Lemos S, Ferreira T, Nascimento-Gonçalves E, Rosa E, et al. Murine models of obesity. Obesities. 2022; 2(2): 127-47, CrossRef.

Tanaka S, Nemoto Y, Takei Y, Morikawa R, Oshima S, Nagaishi T, et al. High-fat diet-derived free fatty acids impair the intestinal immune system and increase sensitivity to intestinal epithelial damage. Biochem Biophys Res Commun 2020; 522(4): 971-7, CrossRef.

Simoes ICM, Karkucinska‐wieckowska A, Janikiewicz J, Szymanska S, Pronicki M, Dobrzyn P, et al. Western diet causes obesity‐induced nonalcoholic fatty liver disease development by differentially compromising the autophagic response. Antioxidants 2020; 9(10): 995, CrossRef.

Togo J, Hu S, Li M, Niu C, Speakman JR. Impact of dietary sucrose on adiposity and glucose homeostasis in C57BL/6J mice depends on mode of ingestion: Liquid or solid. Mol Metab. 2019; 27: 22-32, CrossRef.

Shon WJ, Jung MH, Kim Y, Kang GH, Choi EY, Shin DM. Sugar-sweetened beverages exacerbate high-fat diet-induced inflammatory bowel disease by altering the gut microbiome. J Nutr Biochem. 2023; 113: 109254, CrossRef.

Ye M, Joosse ME, Liu L, Sun Y, Dong Y, Cai C, et al. Deletion of IL-6 exacerbates colitis and induces systemic inflammation in IL-10-deficient mice. J Crohns Colitis. 2020; 14(6): 831-40, CrossRef.

Church JS, Renzelman ML, Schwartzer JJ. Ten-week high fat and high sugar diets in mice alter gut-brain axis cytokines in a sex-dependent manner. J Nutr Biochem. 2022; 100: 108903, CrossRef.

Alhendi A, Naser SA. The dual role of interleukin-6 in Crohn's disease pathophysiology. Front Immunol. 2023; 14: 1295230, CrossRef.

Pawłowska-Kamieniak A, Krawiec P, Pac-Kożuchowska E. Interleukin 6: Biological significance and role in inflammatory bowel diseases. Adv Clin Exp Med. 2021; 30(4): 465-9, CrossRef.

Wei HX, Wang B, Li B. IL-10 and IL-22 in Mucosal Immunity: Driving Protection and Pathology. Front Immunol. 2020; 11: 1315, CrossRef.

Jafrin S, Aziz MA, Islam MS. Elevated levels of pleiotropic interleukin-6 (IL-6) and interleukin-10 (IL-10) are critically involved with the severity and mortality of COVID-19: An updated longitudinal meta-analysis and systematic review on 147 studies. Biomark Insights. 2022; 17: 11772719221106600, CrossRef.

McElvaney OJ, Hobbs BD, Qiao D, McElvaney OF, Moll M, McEvoy NL, et al. A linear prognostic score based on the ratio of interleukin-6 to interleukin-10 predicts outcomes in COVID-19. EBioMedicine 2020; 61: 103026, CrossRef.

Li X, Wei X, Sun Y, Du J, Li X, Xun Z, et al. High-fat diet promotes experimental colitis by inducing oxidative stress in the colon. Am J Physiol Gastrointest Liver Physiol. 2019; 317(4): 453-62, CrossRef.

Yamamoto K, Harada N, Yasuda T, Hatoko T, Wada N, Lu X, et al. Intestinal Morphology and Glucose Transporter Gene Expression under a Chronic Intake of High Sucrose. Nutrients. 2024; 16(2): 196, CrossRef.

de Moura e Dias M, dos Reis SA, da Conceição LL, Sediyama CMN de O, Pereira SS, de Oliveira LL, et al. Diet-induced obesity in animal models: points to consider and influence on metabolic markers. Diabetol Metab Syndr 2021; 13(1): 32, CrossRef.

Régnier M, Rastelli M, Morissette A, Suriano F, Le Roy T, Pilon G, et al. Rhubarb supplementation prevents diet-induced obesity and diabetes in association with increased akkermansia muciniphila in mice. Nutrients. 2020; 12(10): 2932, CrossRef.

Nakase H, Sato N, Mizuno N, Ikawa Y. The influence of cytokines on the complex pathology of ulcerative colitis. Autoimmun Rev 2022; 21(3): 103017, CrossRef.

Meiliana A, Wijaya A. Update on obesity: Induced inflammation to cause cardiometabolic diseases. Indones Biomed J. 2022; 14(2): 116-38, CrossRef.

Andari D, Khan FI, Jakfar SI. Methanol extract of katuk (Sauropus androgynus) leaves as an anti-inflammatory agent: Animal study in carrageenan-induced rat models of inflammation. Mol Cell Biomed Sci. 2022; 6(3): 129-34, CrossRef.

Puspitaningrum I, Ikawati M, Fakhrudin N, Nurrochmad A. Immunomodulatory effect of dioscorea esculenta L. on NF-κB, TLR-4, TNF-α, and IL-10 expressions in LPS-stimulated RAW 264.7 mouse macrophages. Indones Biomed J. 2025; 17(3): 307-16, CrossRef.

Rahardhian MRR, Ardiansyah F, Susilawati Y, Wilar G, Sumiwi SA, Levita J, et al. Immunomodulatory and acute toxicity studies of peronema canescens jack leaves: in vivo hematological analysis and in vitro IL-6 gene expression inhibition. Indones Biomed J. 2025; 17(2): 295-306, CrossRef.

Monica E, Hasanah PD, Fadillah A, Aulia R, Sulistijono E, Wibowo S. Administration of vitamin D3 improves hemoglobin level by regulating TNF-α and IL-6 in DSS-induced colitis mice. Indones Biomed J. 2020; 12(2): 130-5, CrossRef.

Suswita R, Alvarino, Darwin E, Jamsari. Lactococcus lactis D4 has potential effect to alleviate inflammation and reverse dysbiosis in colitis rat model. Indones Biomed J. 2024; 16(2): 199-207, CrossRef.

Fu XL, Duan W, Su CY, Mao FY, Lv YP, Teng YS, et al. Interleukin 6 induces M2 macrophage differentiation by STAT3 activation that correlates with gastric cancer progression. Cancer Immunol Immunother. 2017; 66(12): 1597-608, CrossRef.

Sa'adah NAM, Ardiansyah E, Fadlilah DN, Izati R, Al-Faizah BN, Kavitarna SA, et al. Green tea yogurt supplemented with L. paracasei E1 microcapsules increases erythrocyte counts and B cell development in high-fat fructose diet mice. Mol Cell Biomed Sci. 2025; 9(1): 58-68, CrossRef.

Zhou D, Li Y. Gut microbiota and tumor-associated macrophages: potential in tumor diagnosis and treatment. Gut Microbes. 2023; 15(2): 2276314, CrossRef.

Febriza A, Ridwan R, As'ad S, Kasim VN, Idrus HH. Adiponectin and its role in inflammatory process of obesity. Mol Cell Biomed Sci. 2019; 3(2): 60-6, CrossRef.




DOI: https://doi.org/10.18585/inabj.v17i5.3807

Copyright (c) 2025 The Prodia Education and Research Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

 

Indexed by:

                  

                     

          

 

 

The Prodia Education and Research Institute