December 21, 2007

Discovery Lecture explores ‘Mighty mice,’ metabolism

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Richard Hanson, Ph.D., left, engages the audience during his Discovery Lecture last week. (photo by Mary Donaldson)

Discovery Lecture explores ‘Mighty mice,’ metabolism

Displaying an energy that rivals his recent achievement — a genetically engineered “mighty mouse” that can run on a treadmill for up to six hours without stopping — Richard Hanson, Ph.D., told the tale of the enzyme responsible for this amazing feat, phosphoenolpyruvate carboxykinase (PEP-CK), and its role in metabolism at last week's Discovery Lecture.

Hanson, the Leonard & Jean Skeggs Professor of Biochemistry at Case Western Reserve University School of Medicine in Cleveland, Ohio, has devoted his career to studying the enzyme, which catalyzes the key step in gluconeogenesis (glucose production) in the liver.

These “mighty” mice, which over-express PEP-CK in skeletal muscle, eat more, yet stay fitter and trimmer than normal mice. They also live longer and can breed until the ripe old age of 2.5 years — an age by which most mice have already died.

But why would over-expressing this enzyme in skeletal muscle cause such dramatic physical effects?

“Only the liver and kidney cortex make and release glucose,” he said. But the enzyme is present in a broad variety of tissues. “So what's (the enzyme's) biological role in these other tissues?”

Hanson offered some insights into this question, detailing his findings about PEP-CK's possible roles in metabolic processes other than glucose production.

He also offered some perspective on the importance of traditional metabolism research in the age of molecular biology. Reflecting on the shift to molecular studies, he noted that “metabolism had become a 'dead letter.' The tragedy… is that we lost a generation of people studying metabolism.”

Even he was drawn to studying its regulation at the genetic level.

“It's a complicated gene,” he said. “This really kept me in business…and is the reason that I'm not in Florida clipping coupons as a retired scientist,” he quipped.

“But I think we're seeing a resurgence of metabolism because of diabetes and obesity and many of the metabolic diseases that we'd all agree plague mankind.”

For a complete schedule of the Discovery Lecture Series and archived video of previous lectures, go to