Fructose Metabolism: the Pathogenic Potential of a Little Molecule

In recent decades, the use of fructose in diet has increased worldwide, and coincided with increase of obesity, metabolic syndrome, diabetes, and non-alcoholic liver disease. This review presents molecular aspects of fructose metabolism, its characteristics and contemporary knowledge about control mechanisms in order to answer how this small molecule can exert pathogenic effects. When present in small, physiological amounts, fructose actually exerts protective glycoregulatory effects. However, long-term exposure to supraphysiological amounts of fructose creates conditions for the development of certain pathological states. In such conditions, lipogenesis is intensified causing dyslipidemia, gluconeogenesis is also intensified leading to hyperglycemia and compensatory hyperinsulinemia, while insulin signaling through IP3K/Akt is blocked. Moreover, exposure to high fructose levels can induce inflammation, redox balance disruption and a decline in energy synthesis. It is most likely that the ability of the liver to metabolize large amounts of fructose and the absence of autoregulatory and hormonal control mechanisms are responsible for pathogenic potential of fructose.