1. Home
  2. Vol 5, No 2 (2026)
  3. Ore

Metabolic Responses of BALB/c Mice to a Short-Term Fructose Feeding via Drinking Water – a Preliminary Report

Ayokanmi Ore(1), Saheed Oladele Gbadamosi(2), Samuel Abiodun Kehinde(3), Divine Favour Alexander(4), Amarachi Kosisochukwu Okeke(5),


(1) Biochemistry Programme, Faculty of Natural Sciences, Ajayi Crowther University, Oyo, Nigeria
(2) Biochemistry Programme, Faculty of Natural Sciences, Ajayi Crowther University, Oyo, Nigeria
(3) Department of Environmental Health Science, Faculty of Basic Medical Sciences, Ajayi Crowther University, Oyo, Nigeria
(4) Biochemistry Programme, Faculty of Natural Sciences, Ajayi Crowther University, Oyo, Nigeria
(5) Biochemistry Programme, Faculty of Natural Sciences, Ajayi Crowther University, Oyo, Nigeria
Corresponding Author

Abstract


Excessive fructose consumption has been linked to metabolic dysregulation and liver injury, particularly Metabolic-Dysfunction Associated Steatotic Liver Disease (MASLD). However, there remains insufficient information on the early-stage metabolic and hepatic responses to fructose, especially in BALB/c mice. This preliminary study was designed to evaluate the metabolic and hepatic tissue responses of BALB/c mice to graded fructose intake via drinking water. BALB/c mice (18) were randomly divided into control, 20% fructose and 30% fructose groups. Mice were provided ad libitum access to a diet and drinking water containing 0%, 20% or 30% fructose. All treatments lasted for twenty-one (21) days, during which body weights were monitored weekly. Plasma glucose, insulin, lipids and liver function indices were quantified in the plasma. Additionally, biomarkers of oxidative stress and inflammation were assessed in liver homogenates. Liver sections from the various groups were fixed in neutral buffered formalin and subjected to histopathological examination after hematoxylin and eosin staining. Fructose intake for 21 days induced significant weight gain in mice administered 30% fructose relative to the control group. Total cholesterol and triglyceride levels increased significantly (p < 0.05) in fructose-treated mice compared with the control. There was also a significant increase (p < 0.05) in the oxidative stress biomarker (malondialdehyde, MDA) level, followed by a significant decrease in levels/activities of hepatic antioxidants (Reduced Glutathione (GSH), Glutathione peroxidase (GSH-Px), Superoxide Dismutase (SOD) and Catalase, CAT). Additionally, the level of nitric oxide (NO) and TNF-? increased in liver homogenate relative to the control, followed by an increase in plasma hepatic biomarkers (ALT and AST). The control group showed a normal liver histological pattern, while mice administered 20% fructose showed mild hepatic histological alterations. In contrast, 30% fructose administration induced more pronounced hepatic injury characterised by moderate centrilobular congestion, inflammatory cell infiltration within portal regions, and microvesicular steatosis. Fructose consumption via drinking water induces dose-dependent metabolic and hepatic alterations in BALB/c mice, with higher concentrations promoting steatosis, inflammation, and early features of hepatocellular injury. These findings support the role of high dietary fructose in the onset of metabolic liver dysfunction and provide a foundation for further investigation into underlying molecular mechanisms.

Keywords


Fructose, Metabolic dysregulation, Hepatic steatosis, Oxidative stress, Liver injury

References


Abdelmalek, M. F., Suzuki, A., Guy, C., Unalp-Arida, A., Colvin, R., Johnson, R. J., & Diehl, A. M. (2010). Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology, 51(6), 1961–1971. https://doi.org/10.1002/hep.23535

Baharuddin B. (2025). The metabolic and molecular mechanisms linking fructose consumption to lipogenesis and metabolic disorders. Clinical nutrition ESPEN, 69, 63–68. https://doi.org/10.1016/j.clnesp.2025.06.042

Bhattacharjee, P., Fadlaoui, A., Ryan, C. E., Carlson, C. B., Zhang, D., & Sunny, N. E. (2025). Induction of Fructose Mediated De Novo Lipogenesis Coexists with the Upregulation of Mitochondrial Oxidative Function in Mice Livers. The Journal of nutrition, 155(6), 1768–1781. https://doi.org/10.1016/j.tjnut.2025.04.030

Caliceti, C., Calabria, D., Roda, A., & Cicero, A. F. G. (2017). Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical Review. Nutrients, 9(4), 395. https://doi.org/10.3390/nu9040395

Elliott, S. S., Keim, N. L., Stern, J. S., Teff, K., & Havel, P. J. (2002). Fructose, weight gain, and the insulin resistance syndrome. The American Journal of Clinical Nutrition, 76(5), 911–922. https://doi.org/10.1093/ajcn/76.5.911

Geidl-Flueck, B., & Gerber, P. A. (2023). Fructose drives de novo lipogenesis affecting metabolic health. The Journal of endocrinology, 257(2), e220270. https://doi.org/10.1530/JOE-22-0270

Gornall, A. G., Bardawill, C. J., & David, M. M. (1949). Determination of serum proteins by means of the biuret reaction. Journal of Biological Chemistry, 177, 751–766.

Green, L. C., Wagner, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S., & Tannenbaum, S. R. (1982). Analysis of nitrate, nitrite, and nitrate in biological fluids. Analytical Biochemistry, 126, 131–138.

Gross, R. T., Bracci, R., Rudolph, N., Schroeder, E., & Kochen, J. A. (1967). Hydrogen peroxide toxicity and detoxification in the erythrocytes of newborn infants. Blood, 29, 481–493.

Hannou, S. A., Haslam, D. E., McKeown, N. M., & Herman, M. A. (2018). Fructose metabolism and metabolic disease. The Journal of clinical investigation, 128(2), 545–555. https://doi.org/10.1172/JCI96702

Herman, M. A., & Birnbaum, M. J. (2021). Molecular aspects of fructose metabolism and metabolic disease. Cell metabolism, 33(12), 2329–2354. https://doi.org/10.1016/j.cmet.2021.09.010

Inci, M. K., Park, S. H., Helsley, R. N., Attia, S. L., & Softic, S. (2023). Fructose impairs fat oxidation: Implications for the mechanism of western diet-induced NAFLD. The Journal of Nutritional Biochemistry, 114, 109224. https://doi.org/10.1016/j.jnutbio.2022.109224

Jegatheesan, P., & De Bandt, J. P. (2017). Fructose and NAFLD: The Multifaceted Aspects of Fructose Metabolism. Nutrients, 9(3), 230. https://doi.org/10.3390/nu9030230

Jollow, D. J., Mitchell, J. R., Zampaglione, N., & Gillette, J. R. (1974). Bromobenzene-induced liver necrosis: Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology, 11, 151–169.

Jung, S., Bae, H., Song, W. S., & Jang, C. (2022). Dietary Fructose and Fructose-Induced Pathologies. Annual review of nutrition, 42, 45–66. https://doi.org/10.1146/annurev-nutr-062220-025831

Kanuri, G., Spruss, A., Wagnerberger, S., Bischoff, S. C., & Bergheim, I. (2011). Fructose-induced steatosis in mice: Role of plasminogen activator inhibitor-1, microsomal triglyceride transfer protein and NKT cells. Laboratory Investigation, 91(6), 885–895. https://doi.org/10.1038/labinvest.2011.59

Kanuri, G., Spruss, A., Wagnerberger, S., Bischoff, S. C., & Bergheim, I. (2011). Role of tumor necrosis factor ? (TNF?) in the onset of fructose-induced nonalcoholic fatty liver disease in mice. The Journal of nutritional biochemistry, 22(6), 527–534. https://doi.org/10.1016/j.jnutbio.2010.04.007

Lim, J. S., Mietus-Snyder, M., Valente, A., Schwarz, J. M., & Lustig, R. H. (2010). The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nature Reviews Gastroenterology & Hepatology, 7(5), 251–264. https://doi.org/10.1038/nrgastro.2010.41

Lujan, L. M. L., Molina, N. M., Guerrero-Magaña, D. E., Vargas-Mendoza, N., Martínez-García, M., Morales-González, J. A., Madrigal-Santillán, E., & Morales-González, Á. (2026). Role of excessive fructose consumption on liver health. Clinical Nutrition Open Science, 65, 100613. https://doi.org/10.1016/j.nutos.2025.12.007

Mamikutty, N., Thent, Z. C., & Haji Suhaimi, F. (2015). Fructose-Drinking Water Induced Nonalcoholic Fatty Liver Disease and Ultrastructural Alteration of Hepatocyte Mitochondria in Male Wistar Rat. BioMed research international, 2015, 895961. https://doi.org/10.1155/2015/895961

Mamikutty, N., Thent, Z. C., Sapri, S. R., Sahruddin, N. N., Mohd Yusof, M. R., & Haji Suhaimi, F. (2014). The establishment of metabolic syndrome model by induction of fructose drinking water in male Wistar rats. BioMed research international, 2014, 263897. https://doi.org/10.1155/2014/263897

Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985). Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 28, 412–419.

Mazzoli, A., Spagnuolo, M. S., Nazzaro, M., Gatto, C., Iossa, S., & Cigliano, L. (2021). Fructose Removal from the Diet Reverses Inflammation, Mitochondrial Dysfunction, and Oxidative Stress in Hippocampus. Antioxidants (Basel, Switzerland), 10(3), 487. https://doi.org/10.3390/antiox10030487

Miao, L., Targher, G., Byrne, C. D., Cao, Y. Y., & Zheng, M. H. (2024). Current status and future trends of the global burden of MASLD. Trends in endocrinology and metabolism: TEM, 35(8), 697–707. https://doi.org/10.1016/j.tem.2024.02.007

Midorikawa, K., Kobayashi, K., Kato, S., Kawanishi, S., Kobayashi, H., Oikawa, S., & Murata, M. (2024). Oxidative DNA damage: Induction by fructose, in vitro, and its enhancement by hydrogen peroxide. Mutation research. Genetic toxicology and environmental mutagenesis, 893, 503719. https://doi.org/10.1016/j.mrgentox.2023.503719

Muriel, P., López-Sánchez, P., & Ramos-Tovar, E. (2021). Fructose and the Liver. International Journal of Molecular Sciences, 22(13), 6969. https://doi.org/10.3390/ijms22136969

Ore, A., & Akinloye, O. A. (2019). Oxidative Stress and Antioxidant Biomarkers in Clinical and Experimental Models of Non-Alcoholic Fatty Liver Disease. Medicina (Kaunas, Lithuania), 55(2), 26. https://doi.org/10.3390/medicina55020026

Özer, N., Dalm?zrak, Ö., Elabiad, S., & Ö?ü?, I. H. (2025). Fructose and insulin: A sweet sabotage hypothesis? Endocrine, 90(3), 1112–1119. https://doi.org/10.1007/s12020-025-04464-9

Softic, S., Gupta, M. K., Wang, G. X., Fujisaka, S., O'Neill, B. T., Rao, T. N., Willoughby, J., Harbison, C., Fitzgerald, K., Ilkayeva, O., Newgard, C. B., Cohen, D. E., & Kahn, C. R. (2017). Divergent effects of glucose and fructose on hepatic lipogenesis and insulin signaling. The Journal of clinical investigation, 127(11), 4059–4074. https://doi.org/10.1172/JCI94585

Softic, S., Stanhope, K. L., Boucher, J., Divanovic, S., Lanaspa, M. A., Johnson, R. J., & Kahn, C. R. (2020). Fructose and hepatic insulin resistance. Critical reviews in clinical laboratory sciences, 57(5), 308–322. https://doi.org/10.1080/10408363.2019.1711360

Spruss, A., Kanuri, G., Wagnerberger, S., Haub, S., Bischoff, S. C., & Bergheim, I. (2009). Toll-like receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice. Hepatology (Baltimore, Md.), 50(4), 1094–1104. https://doi.org/10.1002/hep.23122

Targher, G., Valenti, L., & Byrne, C. D. (2025). Metabolic dysfunction–associated steatotic liver disease. New England Journal of Medicine, 393(7), 683–698. https://doi.org/10.1056/NEJMra2412865

Todoric, J., Di Caro, G., Reibe, S., Henstridge, D. C., Green, C. R., Vrbanac, A., Ceteci, F., Conche, C., McNulty, R., Shalapour, S., Taniguchi, K., Meikle, P. J., Watrous, J. D., Moranchel, R., Najhawan, M., Jain, M., Liu, X., Kisseleva, T., Diaz-Meco, M. T., Moscat, J., … Karin, M. (2020). Fructose stimulated de novo lipogenesis is promoted by inflammation. Nature metabolism, 2(10), 1034–1045. https://doi.org/10.1038/s42255-020-0261-2

Vachliotis, I. D., & Polyzos, S. A. (2023). The Role of Tumor Necrosis Factor-Alpha in the Pathogenesis and Treatment of Nonalcoholic Fatty Liver Disease. Current obesity reports, 12(3), 191–206. https://doi.org/10.1007/s13679-023-00519-y

Varshney, R., & Kale, R. K. (1990). Effect of calmodulin antagonist on radiation-induced lipid peroxidation in microsomes. International Journal of Radiation Biology, 58, 733–743


Full Text: PDF

Article Metrics

Abstract View : 41 times
PDF Download : 5 times

DOI: 10.56534/acjpas.v5i2.199

Refbacks

  • There are currently no refbacks.