Impact of fructose consumption on metabolic and hypertrophy markers in mice liver and heart

Introduction: fructose is widely used as a sweetener in beverages and ultra-processed foods, leading to increased consumption. It is linked to de novo lipogenesis in the liver, and excessive intake is associated with metabolic disorders like insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD), which in turn is related to significant cardiovascular risks. However, its direct effects on the heart remain contradictory, highlighting the importance of studying the liver-heart axis in these pathologies. The aim of this study was to evaluate the effect of dietary fructose on lipidic metabolism and oxidative status in both liver and heart, along with heart hypertrophy in a murine model fed a high fructose diet. Materials and method: male C57BL/6 mice were randomly distributed in two experimental groups: 1) control diet (n=4) (CD; Research Diet INC, D12450B, USA; 10% lipids, 20% protein, 70% carbohydrates) and 2) CD+F (n=7) (FCD; CD plus fructose on water 40% w/v). The following were evaluated: a) General parameters of the liver, adipose tissue, and heart; b) Insulin resistance parameters; c) hepatic steatosis and adipose tissue by histology; d) lipid metabolism parameters (SREBP-1c, FAS, PPAR-α, and ACOX) in liver and heart; e) cardiac hypertrophy and mRNA expression of hypertrophy cardiac markers (ANP, BMP, and β-MHC), and f) oxidative stress markers (Nrf2, HO-1) in liver and heart. Results: fructose consumption led to an increase in visceral adipose tissue, along with the development of grade 2 hepatic steatosis. Insulin resistance was not observed; however, there was a decrease (p<0.05) in insulinemia and HOMA-IR values. An increase (p<0.05) in both pro-lipogenic and pro-lipolytic markers was observed in the liver and heart. While cardiac hypertrophy was not evident, there was an elevation (p<0.05) in cardiac hypertrophy mRNA markers. Oxidative stress markers did not increase in the liver but were elevated (p<0.05) in the heart. Conclusions: long term high fructose diet induces lipid accumulation in the liver, along with inducing a pre-state of cardiac hypertrophy. Our study highlights the necessity of standardizing the study of fructose supplementation in time, dose and animal model used.