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June 2007 Issue

Zebrafish shown in a "treadmill" researchers are using to study physical activity levels.
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Fidgety Fish Could Hold Weight-Loss Clues

Published June 2007

Your tap-happy colleague in the next cube over might be a real annoyance, but her compulsion to fidget could be keeping her slim.


Scientists have shown that leanness is connected to the amount of fidgeting—also called spontaneous physical activity or SPA—that people do. But what makes one person move while the next person sits virtually motionless?


The answer, say UC researchers, might come from an unlikely subject.


A team of scientists, led by Jay Hove, PhD, is hoping that the zebrafish, or Danio rerio, will offer important clues about SPA. And he says those clues could one day be used to target obesity.


Hove, an assistant professor of genome science, leads the Genome Research Institute’s Zebrafish and Medaka Model Organisms Lab—one of the largest laboratories of its kind in the United States, with the capacity to house more than 250,000 of the striped freshwater tropicals.


These rapid developers (a zebrafish has a beating heart 22 hours after conception and is fully developed in just five to seven days) are already used to study many organ systems and diseases. Establishing them as a model for obesity, Hove says, is a fairly unique concept—but it’s not without advantages.


Animals—that includes people—gain weight when they take in (eat) more energy than they use. Energy is expended through physical activity (spontaneous or not) and through thermogenesis—the process used to maintain a certain body temperature.


Because fish are “cold blooded,” they don’t use energy to keep warm like mammals do. They burn their calories largely through activity alone. So, looking into the fishbowl might offer scientists a clearer picture of how “fidgeting” affects caloric balance and which molecules may control that process. 


Initial studies of the fish as an obesity model were promising, leading the National Institutes of Health to fund Hove and his colleagues for further research. The team will use that funding—about $430,000 spread over two years—to conduct further studies to establish the zebrafish as a viable study subject.


Using a modified version of the monitoring software used to track movement in rodents, the team will observe 1,000 fish, separating those considered to be highly active from their more sedentary counterparts.


They will continue tracking movement, and will also measure metabolic rates in still water when the fish are free to move around or stay put, and in a high-tech zebrafish “treadmill.” One of the major measures in this study will be body fat levels, which the investigators predict will differ between a “couch potato” fish and its fellow “fidgeters.”


The scientists will also compare the two fish groups when placed on high- or low-calorie diets, monitoring activity levels for each diet group to see if any of the fish fail to naturally increase activity in response to more calories.


Most important, says Hove, specific tissues from “couch potato” and “fidgeting” fish will be screened for differences in genes that are “turned on” or “turned off.” He and his colleagues hope to find a new drug target that may boost a fish’s—and perhaps someday a human’s—SPA.


“It has been clearly shown in humans that changes in SPA in the face of increased dietary calories are the single largest predictor of weight gain,” say Hove. “That’s why understanding the molecular pathways regulating SPA is so important.”


Collaborators on the grant include Karen Seta-Aust, PhD, department of genome science, and Randy Seeley, PhD, and Matthias Tschöp, MD, both of the department of psychiatry and UC’s Obesity Research Center.

Watch how "fidegty" zebrafish are put to the test in a high-tech treadmill.

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