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

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.