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Survival of the Fattest
A recent study by UNLV researchers using the world’s fattest fruit flies is providing a new model to investigate obesity-related heart dysfunction.
Fruit flies have emerged as an excellent model to investigate the genetic causes and physiological consequences of obesity. But to study the effects, scientists must first obtain overweight fruit flies.
In previous experiments, researchers around the world have made their test flies obese by feeding them a high-fat diet or by genetic manipulation. Life sciences professor Allen Gibbs and Ph.D. student Christopher Hardy took a unique approach; they used experimental evolution, or natural selection, to grow obese flies.
While dietary and genetic changes that cause obesity in flies have been demonstrated to induce heart dysfunction, there have been no studies investigating how obesity affects the heart in laboratory-evolved flies. This process has allowed them to produce the world’s fastest fruit flies, according to Gibbs. A normal fly weighs one milligram, while Gibbs and Hardy’s weigh in at 1.5 milligrams.
“We are using evolution in the lab,” said Gibbs, who started the selection process in 2007 with 10,000 genetically different flies. “The ones that have the right genes to live without food are the ones that survive. We do this over and over with the flies that survive and eventually get those that survive starvation longer and longer every generation. It is essentially survival of the fattest.”
The research team discovered that the hearts of starvation-selected fruit flies are dilated and don’t contract properly. This appears to correlate with large fat deposits along the dorsal cuticle, which alter the anatomical position of the heart. However, heart function in their flies can return to healthy levels through prolonged fasting.
The findings provide a new model to investigate obesity-associated heart dysfunction. “While obesity has many pathophysiological effects, the ability to store excess lipids may have an ecological advantage in the context of starvation resistance,” Hardy said. “In nature, lipids stored within the fat body may be used to survive periods where nutrients aren’t readily available. In the lab, selection for starvation-resistance in fruit flies leads to correlated increases in stored lipids, but has evolutionary costs, including heart disease, reduced movement, and disruptive sleeping patterns.”
Gibbs noted that genetics is the primary reason fruit flies are studied as it relates to obesity-associated diseases. “There has been more than a century of intense research on genetics and flies. There is a lot that we can do with flies that you can’t do with humans or other mammals, like mice,” he said. “One thing we have done is sequence the entire genetic code for our flies, which allows us to determine the genes that affect obesity in our flies. We can then study if similar genes are found in mice, and eventually humans.”
The findings were published in the September issue of the American Journal of Physiology.
The research team also included researchers from the Sanford Burnham Medical Research Institute, University of Virginia School of Medicine, and Duke University School of Medicine.
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