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

Fructose 2,6-bisphosphate (Fru-2,6-P 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 Pf...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2008-01, Vol.365 (2), p.291-297
Main Authors: Duran, Joan, Navarro-Sabate, Aurea, Pujol, Anna, Perales, Jose C., Manzano, Anna, Obach, Mercè, Gómez, Marta, Bartrons, Ramon
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Animals
DIET
ENZYMES
FRUCTOSE
Fructose 2,6-bisphosphate
GENES
Gluconeogenesis
GLYCOLYSIS
LIPIDS
LIVER
Liver - physiology
METABOLIC DISEASES
Mice
Mice, Transgenic
NEOPLASMS
Obesity
PHOSPHOENOLPYRUVATE
Phosphofructokinase-2 - genetics
Phosphofructokinase-2 - metabolism
TRANSGENIC MICE
Up-Regulation
Weight Gain - physiology
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Summary:Fructose 2,6-bisphosphate (Fru-2,6-P 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 2 levels in the liver. Our results demonstrate that in diet-induced obesity, high Fru-2,6-P 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2007.10.181