OHSU Scientists Develop New Method For Studying Obesity: Fish

02/26/11  Portland, Ore.

Researchers at Oregon Health & Science University have developed a unique new method for researching obesity and its treatments - by studying fish. Newly published data demonstrate zebrafish, small fish that measure between one and two inches in length when fully grown, share many traits with humans with regard to the regulation of body weight. This discovery demonstrates that the zebrafish are relevant for human and animal weight and obesity studies. The study is published in the July edition of The FASEB Journal.

“Traditionally, researchers have studied weight and obesity by observing humans and mice. In fact, many of our lab’s previous findings about the brain’s role in weight control took place in mice. When combined with human studies, these findings greatly expanded on our knowledge regarding weight regulation in both species,” explained Roger Cone, Ph.D., director for the Center for Weight Regulation and Associated Disorders at OHSU, and senior author of the paper. “Now, these tiny zebrafish have the ability to provide us with even greater insight into the many factors that control weight gain.”

In conducting their research, Cone and his colleagues focused on a group of specialized brain cells that exist in humans and other mammals and are collectively called the adipostat. The adipostat, the longtime research focus of Cone and others, monitors and regulates body weight. It operates much like a programmable home thermostat that tracks temperature and regulates heating or cooling. In the case of adipostat, the brain mechanism tracks weight and makes adjustments, such as burning more calories or increasing appetite, to preserve a person’s weight at times of feast or famine.

“When this system is broken, significant weight gain can occur,” said Cone. “In addition, the system can cause a person to be underweight if it is not working properly, a condition known as cachexia or wasting disease. It can also become a major hurdle to losing weight and keeping it off. For dieters, the adipostat is literally fighting to keep you at your heavier weight.” 

In determining whether zebrafish are a good animal for studying obesity, Cone and his colleagues first needed to confirm the existence of the adipostat in the species. They did so by breeding animals so that an important part of the adipostat - specifically, the central melanocortin system - was blocked. Just as is the case is with humans, where the adipostat breakdown can occur naturally, the specially bred zebrafish gained weight. The findings offer researchers a valuable new avenue for studying and treating the nation’s obesity epidemic. The discovery also demonstrates that the adipostat is likely an ancient and basic vertebrate body function that even predates the evolution of mammals.

“Zebrafish are small, easy-to-care-for animals with very well documented genetic profiles,” explained Cone. “Also, just like mice, zebrafish genetics related to the regulation of body weight nicely corresponds with humans. The real advantage of the zebrafish is that we can mutate every single gene in the entire genome and identify all of the genes involved in obesity and diabetes; this type of comprehensive study cannot be done in the mouse, rat or any other vertebrate model system at the current time. This information will be incredibly valuable in understanding complex diseases, and thus developing better medications to assist those who are fighting obesity and diabetes.”

About Overweight and Obesity
*    Most adults are either overweight or obese. A person who is considered overweight has a body mass index (BMI) between 25 and 29.9. An obese individual has a BMI over 29.9.
*    According to the Centers for Disease Control, obesity has sharply increased in adults and children since the mid 1970s.
*    According to a recent survey (2003-2004), 13.9 percent of children ages 2 to5 are considered overweight; 18.8 percent of children ages 6 to11 are overweight. 
*     Being overweight increases a person’s disease risks for hypertension, type 2 diabetes, heart disease, stroke, sleep apnea, respiratory problems, some forms of cancer and many other diseases.