Scientists find 'skinny' gene's value (10/9/2007)

Scientists have learned the role of a key gene in the war on weight, a tiny bundle of DNA discovered in fruit flies 50 years ago by Winifred Doane, a professor emeritus at ASU.

The gene, which controls fat formation, functions in many cells throughout the bodies of a broad array of animals, according to research published in the journal Cell Metabolism by lead author Jae Myoung Suh. The work was done with a team from the laboratory of Jonathan Graff, associate professor of developmental biology and internal medicine at the University of Texas Southwestern Medical Center.

The finding is an extension of work begun by Doane while a graduate student at Yale University and continued while at ASU. Studying why some fruit flies are packed with fat while others are not, Doane traced the cause to a single gene that she called "adipose."

"Because adipose was ahead of its time, I had set it aside," Doane says. "But I recognized its potential value, and so I maintained mutant stocks containing it all these years, lest it be lost."

When Doane retired in 1998, she established a collaborative study with researchers in Göttingen, Germany, at DeveloGen AG and the Max Planck Institute, to clone and sequence adipose's DNA. The research showed that the gene is present in mice and humans and unraveled the structure of the gene's product, a protein never seen before.

This study, published in 2003, laid the groundwork for the research in Graff's laboratory, where Suh unfolded the function of the "skinny gene" using mutant adipose fly stocks provided by Doane.

In addition to validating adipose's anti-obesity therapeutic potential, Suh and his colleagues confirmed that adipose is an evolutionarily conserved gene - a gene that remains essentially unchanged throughout evolution.

All of which was suspected by Doane 50 years ago, when she was without the molecular tools to investigate it further.

"When adipose was discovered, little to nothing was known about the biochemistry of fat metabolism in insects," Doane says. "It was decades before the tools of molecular genetics and gene cloning could be used to sort out the function of this gene.

"Needless to say, it is most gratifying to have my favorite gene finally recognized for what it can offer."

Note: This story has been adapted from a news release issued by Arizona State University

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