Organismal Fructose Metabolism in Health and Non-Alcoholic Fatty Liver Disease

Abstract

NAFLD has alarmingly increased, yet FDA-approved drugs are still lacking. An excessive intake of fructose, especially in liquid form, is a dietary risk factor of NAFLD. While fructose metabolism has been studied for decades, it is still controversial how fructose intake can cause NAFLD. It has long been believed that fructose metabolism solely happens in the liver and accordingly, numerous studies have investigated liver fructose metabolism using primary hepatocytes or liver cell lines in culture. While cultured cells are useful for studying detailed signaling pathways and metabolism in a cell-autonomous manner, it is equally important to understand fructose metabolism at the whole-body level in live organisms. In this regard, recent in vivo studies using genetically modified mice and stable isotope tracing have tremendously expanded our understanding of the complex interaction between fructose-catabolizing organs and gut microbiota. Here, we discuss how the aberrant distribution of fructose metabolism between organs and gut microbiota can contribute to NAFLD. We also address potential therapeutic interventions of fructose-elicited NAFLD.