Overexpression of ubiquitous 6-phosphofructo-2-kinase in the liver of transgenic mice results in weight gain

Joan Duran, Aurea Navarro-Sabate, Anna Pujol, Jose C. Perales, Anna Manzano, Mercè Obach, Marta Gómez, Ramon Bartrons

    Research output: Contribution to journalArticleResearchpeer-review

    15 Citations (Scopus)

    Abstract

    Fructose 2,6-bisphosphate (Fru-2,6-P2) is an important metabolite that controls glycolytic and gluconeogenic pathways in several cell types. Its synthesis and degradation are catalyzed by the bifunctional enzyme 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK-2). Four genes, designated Pfkfb1-4, codify the different PFK-2 isozymes. The Pfkfb3 gene product, ubiquitous PFK-2 (uPFK-2), has the highest kinase/bisphosphatase activity ratio and is associated with proliferation and tumor metabolism. A transgenic mouse model that overexpresses uPFK-2 under the control of the phosphoenolpyruvate carboxykinase promoter was designed to promote sustained and elevated Fru-2,6-P2 levels in the liver. Our results demonstrate that in diet-induced obesity, high Fru-2,6-P2 levels in transgenic livers caused changes in hepatic gene expression profiles for key gluconeogenic and lipogenic enzymes, as well as an accumulation of lipids in periportal cells, and weight gain. © 2007 Elsevier Inc. All rights reserved.
    Original languageEnglish
    Pages (from-to)291-297
    JournalBiochemical and Biophysical Research Communications
    Volume365
    Issue number2
    DOIs
    Publication statusPublished - 11 Jan 2008

    Keywords

    • Fructose 2,6-bisphosphate
    • Gluconeogenesis
    • Glycolysis
    • Obesity
    • Transgenic mice

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