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 and Richard J. Johnson
Additional contact information
Miguel A. Lanaspa: University of Colorado, 12700 East 19th Avenue, Room 7015, Denver, Colorado 80045, USA
Takuji Ishimoto: University of Colorado, 12700 East 19th Avenue, Room 7015, Denver, Colorado 80045, USA
Nanxing Li: University of Colorado, 12700 East 19th Avenue, Room 7015, Denver, Colorado 80045, USA
Christina Cicerchi: University of Colorado, 12700 East 19th Avenue, Room 7015, Denver, Colorado 80045, USA
David J. Orlicky: University of Colorado
Philip Ruzycki: University of Colorado
Christopher Rivard: University of Colorado, 12700 East 19th Avenue, Room 7015, Denver, Colorado 80045, USA
Shinichiro Inaba: University of Colorado, 12700 East 19th Avenue, Room 7015, Denver, Colorado 80045, USA
Carlos A. Roncal-Jimenez: University of Colorado, 12700 East 19th Avenue, Room 7015, Denver, Colorado 80045, USA
Elise S. Bales: University of Colorado
Christine P. Diggle: Leeds Institute of Molecular Medicine, University of Leeds
Aruna Asipu: Leeds Institute of Molecular Medicine, University of Leeds
J. Mark Petrash: University of Colorado
Tomoki Kosugi: University of Colorado, 12700 East 19th Avenue, Room 7015, Denver, Colorado 80045, USA
Shoichi Maruyama: Nagoya University Graduate School of Medicine
Laura G. Sanchez-Lozada: University of Colorado, 12700 East 19th Avenue, Room 7015, Denver, Colorado 80045, USA
James L. McManaman: University of Colorado
David T. Bonthron: Leeds Institute of Molecular Medicine, University of Leeds
Yuri Y. Sautin: University of Florida
Richard J. Johnson: University of Colorado, 12700 East 19th Avenue, Room 7015, Denver, Colorado 80045, USA

Nature Communications, 2013, vol. 4, issue 1, 1-9

Abstract: Abstract 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.

Date: 2013
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms3434 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3434

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms3434

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().