The Hidden Costs of Sweetness: Fructose-Induced Liver Inflammation

Fructose consumption has contributed to the prevalence of obesity, a major risk factor for metabolic disorders like metabolic-associated liver disease (MASLD). Obesity frequently coexists with liver disease, and excessive fructose intake directly promotes MASLD by driving hepatic inflammation, oxidative stress, and metabolic dysfunction. Despite growing research, gaps remain in understanding how dietary fructose leads to liver dysfunction. Many MASLD models rely on supraphysiological fructose levels (60%), which limit their relevance to the human diet. In this study, we investigated how dietary sugars at levels (15%) comparable to that in the Western diet influence liver health. To do so, we analyzed inflammatory, oxidative stress, and metabolic gene expression in mice-fed diets containing 15% fructose, 60% fructose, or standard chow. We fed seventeen male and female mice sugar-based diets for 8 to 23 weeks and analyzed gene expression using quantitative PCR. Mice on 60% and 15% fructose diets showed comparable gene expression patterns, with Nrf2 and Cd36 displaying significant differences. When compared to other sugar types, dextrose and sucrose also induced the expression of similar inflammatory liver markers. Since a 60% fructose diet is known to induce MASLD, our results suggest that even 15% fructose may have similar effects. However, dextrose and sucrose increased both pro- and anti-inflammatory gene expression, making their role in MASLD unclear. These findings highlight the complex relationship between dietary sugars and liver health, emphasizing the need for further research on the long-term effects of different sugar types in MASLD development.