Journal Article

Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome

Asipu, Aruna, Roncal-Jimenez, Carlos A., Inaba, Shinichiro, Sautin, Yuri Y., Li, Nanxing, Cicerchi, Christina, Kosugi, Tomoki, Orlicky, David J., Ishimoto, Takuji, Rivard, Christopher, Petrash, J. Mark, Johnson, Richard J., Bonthron, David T., Sanchez-Lozada, Laura G., Lanaspa, Miguel A., McManaman, James L., Bales, Elise S., Ruzycki, Philip, Maruyama, Shoichi, Diggle, Christine P.

2013

Overview

Carbohydrates with high glycaemic index are proposed to promote the development of obesity, insulin resistance and fatty liver, but the mechanism by which this occurs remains unknown. High serum glucose concentrations are known to induce the polyol pathway and increase fructose generation in the liver. Here we show that this hepatic, endogenously produced fructose causes systemic metabolic changes. We demonstrate that mice unable to metabolize fructose are protected from an increase in energy intake and body weight, visceral obesity, fatty liver, elevated insulin levels and hyperleptinaemia after exposure to 10% glucose for 14 weeks. In normal mice, glucose consumption is accompanied by aldose reductase and polyol pathway activation in steatotic areas. In this regard, we show that aldose reductase-deficient mice are protected against glucose-induced fatty liver. We conclude that endogenous fructose generation and metabolism in the liver represents an important mechanism by which glucose promotes the development of metabolic syndrome. Consumption of high amounts of glucose leads to the development of insulin resistance and metabolic syndrome. Here, Lanaspa et al. show that the hepatic conversion of glucose into fructose is a key step in the development of glucose-induced metabolic syndrome and fatty liver in mice.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 692/308 / 692/420 / 692/699/2743/2037 / Aldehyde Reductase - metabolism / Animals / Body weight / Carbohydrates / Energy Metabolism / Fatty Liver - metabolism / Feeding Behavior / Fructokinases - deficiency / Fructokinases - metabolism / Fructose - biosynthesis / Fructose - metabolism / Glucose - metabolism / Hep G2 Cells / Humanities and Social Sciences / Humans / Liver / Liver - enzymology / Liver - metabolism / Liver - pathology / Liver - physiopathology / Metabolic disorders / Metabolic Syndrome - metabolism / Metabolic Syndrome - pathology / Mice / Mice, Inbred C57BL / Mice, Knockout / multidisciplinary / Obesity / Polymers - metabolism / Science / Science (multidisciplinary)