Fructose and NAFLD: The Multifaceted Aspects of  Fructose Metabolism

Abstract

Among various factors, such as an unhealthy diet or a sedentarity lifestyle, excessive fructose consumption is known to favor nonalcoholic fatty liver disease (NAFLD), as fructose is both a substrate and an inducer of hepatic de novo lipogenesis. The present review presents some well-established mechanisms and new clues to better understand the pathophysiology of fructose-induced NAFLD. Beyond its lipogenic effect, fructose intake is also at the onset of hepatic inflammation and cellular stress, such as oxidative and endoplasmic stress, that are key factors contributing to the progression of simple steatosis to nonalcoholic steatohepatitis (NASH). Beyond its hepatic effects, this carbohydrate may exert direct and indirect effects at the peripheral level. Excessive fructose consumption is associated, for example, with the release by the liver of several key mediators leading to alterations in the communication between the liver and the gut, muscles, and adipose tissue and to disease aggravation. These multifaceted aspects of fructose properties are in part specific to fructose, but are also shared in part with sucrose and glucose present in energy–dense beverages and foods. All these aspects must be taken into account in the development of new therapeutic strategies and thereby to better prevent NAFLD.

Molecular Basis for Pathogenesis of Steatohepatitis: Contemporary Understanding and New Insights

“…Also fructose phosphorylation leads to depletion of ATP, which stimulates increased uric acid synthesis which in turn stimulates production of ROS [81]. Lastly fructose can induce mitochondrial disturbance which lead to disequilibrium between De novo Lipogenesis and VLDL, which promotes alteration of respiratory chain and uncoupling of oxidative phosphorylation with excess ROS production [82,83].…”

Molecular mechanisms of nonalcoholic fatty liver disease: Potential role for 12-lipoxygenase

“…Simple carbohydrates, such as glucose and fructose generate abundant levels of glycerol-3-phosphate, which can be used in triglyceride synthesis. Moreover, as fructokinase is not regulated by insulin, excessive fructose can lead to unregulated production of acetyl-Co-A, which is in turn converted to triglycerides (Jegatheesan & De Bandt, 2017). Diets deficient in essential nutrients can also result in fatty liver.…”

The Dietary Fibers–FODMAPs Controversy

“…because this promotes ectopic triglyceride synthesis and, thereby, increases the risk of developing nonalcoholic fatty liver disease (NAFLD). However, it has been observed that ingestion of nondigestible carbohydrates, including oligosaccharides classified as FODMAPs, may also protect against the onset of NAFLD (4,22).…”