Pathogenic aspects of fructose consumption in metabolic dysfunction-associated steatotic liver disease (MASLD): A narrative review

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to non-alcoholic fatty liver disease (NAFLD), has become a global health concern with a still increasing prevalence. One of the major contributing factors to its pathogenesis is overnutrition. In recent years, a discussion has been started that not only general overnutrition but also specific dietary patterns like the so-called 'Western diet' composed of foods rich in saturated fats, cholesterol, and sugar (especially fructose) but low in fiber and polyunsaturated fats, may contribute to the development of MASLD. Evidence from human (intervention) studies regarding the effects of sugar and especially fructose intake is limited and contradictory with respect to the development of MASLD. Still, some scientific liver societies have incorporated a reduction of sugar-sweetened beverages (SSBs) being rich in fructose in their life-style advice for the treatment of MASLD. Being metabolized independently of insulin, fructose has been proposed to be processed more rapidly than glucose, leading to increased lipogenesis and subsequently to hepatic lipid accumulation. Results of more recent experimental studies suggest that an elevated intake of fructose may also affect gut microbiota composition, alter small intestinal morphology and impair intestinal barrier function subsequently leading to an increased translocation of pathogen-associated molecular patterns (PAMPs) into the portal circulation. In this narrative review we summarize recent findings related to the relationship of fructose intake and MASLD, herein focusing on the gut-liver axis and the discrepancy between studies in humans and model organisms.