Endogenous Fructose Production and Metabolism in the Liver Contributes to the Development of Metabolic Syndrome

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

Research output: Contribution to journalArticlepeer-review

174 Scopus citations


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 reductasedeficient 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.

Original languageEnglish
Article number2434
Pages (from-to)1-8
Number of pages8
JournalNature communications
StatePublished - Sep 10 2013


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