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Mighty Mouse

Phosphoenolpyruvate carboxykinase (PEPCK-C) is an enzyme that is involved in gluconeogenesis in the liver and kidney cortex and in glyceroneogenesis in the liver and white and brown adipose tissue. The enzyme is also present in a wide variety of mammalian tissues such as the small intestine, colon, mammary gland, adrenal gland, lung, and muscle. However, its function in these tissues remains unclear.

PEPCK-Cmus mice contain less body fat than wild-type mice.

In this Paper of the Week, Parvin Hakimi and colleagues overexpressed the gene for PEPCK-C in the skeletal muscle of transgenic mice to assess the metabolic and physiological consequences. Surprisingly, they discovered the transgenic mice were 7 times more active than control mice. The mice were able to exercise on a treadmill for 2-6 km, as compared to 0.2 km for wild-type mice, and they ran twice as fast as control mice. This greatly enhanced exercise capacity was accompanied by a large increase in mitochondria and triglyceride content in the skeletal muscle. The transgenics were long-lived and retained their enhanced exercise capacity, as well as their fecundity, into murine old age. The mice overexpressing the gene for PEPCK-C also had very little body fat, despite eating 60% more than control mice. The authors conclude that overexpression of PEPCK-C repatterns energy metabolism and leads to greater longevity.

FOOTNOTES

See referenced article, J. Biol. Chem. 2007, 282, 32844-32855

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