Overexpression of ubiquitous 6-phosphofructo-2-kinase in the liver of transgenic mice results in weight gain
- Unitat Bioqui'mica i Biologia Molecular, Departament de Ciencies Fisiologiques, Campus de Ciencies de la Salut, IDIBELL, Universitat de Barcelona, Feixa Llarga s/n, 08907 L'Hospitalet, Barcelona (Spain)
- UAT-CBATEG Unitat d'Animals Transgenics, Centre de Biotecnologia Animal i Terapia Genica, Universitat Autonoma de Barcelona (Spain)
- Unitat de Biofi'sica, Departament de Ciencies Fisiologiques, Campus de Ciencies de la Salut, IDIBELL, Universitat de Barcelona, Barcelona (Spain)
Fructose 2,6-bisphosphate (Fru-2,6-P{sub 2}) 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-P{sub 2} levels in the liver. Our results demonstrate that in diet-induced obesity, high Fru-2,6-P{sub 2} 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.
- OSTI ID:
- 21043573
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 365, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2007.10.181; PII: S0006-291X(07)02347-9; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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