Fructose and Nonalcoholic Fatty Liver Disease

FRANCINI F; MASSA ML; GAGLIARDINO JJ

Dietary Sugars. Chemistry, Analysis, Function and Effects

RSC Publishing

Lugar: Cambridge; Año: 2012; p. 751 - 769

Nonalcoholic fatty liver disease (NAFLD) is an important emerging public health problem which is expanding worldwide. NAFLD is the liver component of the metabolic syndrome, frequently associated with obesity, type 2 diabetes (T2DM) and cardiovascular disease. Several authors have suggested that the marked increase in the intake of high fructose corn syrups and refined carbohydrates registered in the last decades is partly responsible for the current epidemics of obesity and T2DM. Since the liver is the primary site for fructose extraction and metabolism due to the existence of a ?fructose pathway?, its high intake provides an uncontrolled amount of substrates for de novo lipogenesis. The mechanism by which fructose activates lipogenesis, however, is complex and involves several transcription regulators: sterol regulatory element binding protein (SREBP), carbohydrate regulatory element binding protein (ChREBP), and transcription factor X-box binding protein (XBP)1. Other mechanisms involved in the process by which the high fructose intake induces NAFLD in rodents and human beings are the inflammatory cascade activated by tumor necrosis factor á-receptor (TNFR), the hepatic leptin resistance that reduces fatty acid oxidation via adenosine monophosphate-activated protein kinase (AMPK) and PPARá, and the reprogramming of genes involved in lipid and carbohydrate metabolism through epigenetic mechanisms.