An Investigation into the Effects of Chronic High Fructose Consumption on Liver Histology, Triglyceride Content and Gene Expression in Male Sprague-Dawley Rats

Abstract

Background: Chronic high fructose intake is associated with the metabolic syndrome (MetS) and metabolic-dysfunction associated fatty liver disease (MAFLD). Fructose metabolised in the liver is not subject to the same strict regulation as glucose, and high fructose intake can therefore increase lipid production and storage, leading to detrimental metabolic changes. Fructose may also induce hypertension and cardiac remodeling, with mechanisms yet to be fully understood. Fibroblast growth factor 21 (Fgf21), elevated during metabolic stress, may play a role in mitigating fructose-induced damage. Aims: The aim of this master's project was to investigate the effects of a high fructose intervention on liver histology, liver triglyceride content, and liver gene expression in an experimental rat model of MAFLD. Methods: 24 male Sprague-Dawley rats were previously randomised into a fructose group and a control group for 16 weeks. Both groups were given an ad-libitum standard chow diet, and 15% fructose was administered to the drinking water of the fructose group. All rats were sacrificed at week 16 with liver biopsies collected and stored for approximately 1 year prior to this project. In this project, Hematoxylin and Eosin (H&E) staining, Picro Sirius Red (PSR) staining, and Oil Red O (ORO) staining were performed on liver sections collected from these biopsies. A triglyceride assay was used to quantify the triglyceride content in the livers, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to look at differences in gene expression related to inter-organ crosstalk, fatty acid metabolism, cellular stress, inflammation, and fibrosis. Results: The amount of macrovesicular and microvesicular hepatic steatosis, lipid droplets, and triglyceride content were significantly higher in the fructose group compared to the controls although there was no difference in liver collagen deposition between the groups. mRNA levels of Atf4 and Fgf21, related to cellular stress and possibly inter-organ crosstalk, was upregulated in the fructose group, whereas Pdk4, important for fine-tuning the balance between glucose and fatty acid metabolism, was downregulated. Conclusion: The results from this master's project show that chronic consumption of a 15% fructose solution alters liver metabolism and increases hepatic steatosis but does not induce collagen deposition.