Dietary fructose: from uric acid to a metabolic switch in pediatric metabolic dysfunction-associated steatotic liver disease.

Abstract

Fructose consumption in pediatric subjects is rising, as the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Despite increasing evidence supporting the detrimental effects of fructose in the development of Metabolic Syndrome (MetS) and its related comorbidities, the association between fructose intake and liver disease remains unclear, mainly in youths. The current narrative review aims to illustrate the correlation between fructose metabolism and liver functions besides its impact on obesity and MASLD in pediatrics. Fructose metabolism is involved in the liver through the classical lipogenic pathway via de novo lipogenesis (DNL) or in the alternative pathway via uric acid accumulation. Hyperuricemia is one of the main features of MALSD patients, underlining how uric acid is growing interest as a new marker of disease. Observational and interventional studies conducted in children and adolescents, who consumed large amounts of fructose and glucose in their diet, were included. Most of these studies emphasized the association between high fructose intake and weight gain, dyslipidemia, insulin resistance, and MASLD/MASH, even in normal-weight children. Conversely, reducing fructose intake ameliorates liver fat accumulation, lipid profile, and weight. In conclusion, fructose seems a potent inducer of both insulin resistance and hepatic fat accumulation.