UF study suggests dieters shouldn't give up
- slimming hormone waits to be unleashed
| By Tom Nordlie
GAINESVILLE, Fla. - Need motivation to keep those New Year's resolutions to eat better and get more exercise? A University of Florida study in rats suggests dieters who persevere long enough to lose a few pounds may be rewarded with help from a slimming hormone that's otherwise stifled by excess fat.
Described in the current issue of Obesity Research, the study showed adult rats fattened on a high-calorie diet returned to their original weights when scientists used gene therapy to produce the hormone, called leptin, in the rodents' brains, said Satya Kalra, a UF College of Medicine professor of neuroscience who led the study. Leptin is produced by mammals, including people. The findings suggest the hormone could eventually provide betterweight-control methods; today they're a reminder that unwanted pounds are best fought with persistence and prevention.
"The take-home message (of our study) is it's very important that we maintain a healthy lifestyle," said Kalra, a member of UF's McKnight Brain Institute. "That includes a lot of energy expenditure through exercise and tight control on calorie intake."
The number of Americans with weight problems has skyrocketed in recent decades, according to the Centers for Disease Control and Prevention. Currently, almost 59 million Americans are considered obese, meaning that they have a body mass index of 30 or more. Body mass index is a measurement of fat in relation to lean body mass.
Leptin, produced in mammals' fat cells, helps regulate energy use by signaling the brain to reduce appetite and burn more calories, Kalra said. But there's a caloric Catch-22: Overweight mammals produce more leptin, so much that it impairs the very mechanism that should eliminate excess fat.
"For reasons unknown, when leptin levels are increased in theblood (leptin is) ineffective in performing its normal function - this is sometimes referred to as leptin resistance," Kalra said. "It increases more quickly if the animal consumes a diet that's very rich in calories."
For several years, Kalra and his wife Pushpa Kalra, a UF professor of physiology and functional genomics, have sought to overcome leptin resistance in rats and mice by delivering leptin-producing genes to the hypothalamus, an area of the brain that controls many basic body functions and contains receptors activated by leptin. The current study, funded by a 5-year, $1.9 million grant from the National Institutes of Health, focused on a tiny subdivision of the hypothalamus called the paraventricular nucleus.
"Most of the data (from past studies) indicate that the paraventricular nucleus is one of the most important targets for the action of neurotransmitters that stimulate or inhibit appetite, and also the neural circuits that increase energy expenditure," Satya Kalra said.
Although the paraventricular nucleus works in tandem with other structures in the hypothalamus, the UF researchers wanted to determine whether leptin could be successfully produced there. Besides the Kalras,the team included Michela Bagnasco, Michael Dube and Adi Katz.
The study used 30 adult female rats, separated into two groups. For 80 days, one group was fed standard rat chow containing 11 percent fat, while the other received a high-calorie food containing 45 percent fat. At the end of that period scientists injected a solution containing copies of the gene that produces rat leptin into the paraventricular nuclei of six rats from the high-fat group that had become obese. As a control, another six of the obese high-fat rats each received an injection of a solution containing a gene that produces a protein that has no effect on leptin production. The animals fed standard rat chow received no injection.
The vector used to deliver the genes was the apparently harmless adeno-associated virus, used in numerous studies at UF and elsewhere. The rats' body weights and food intakes were monitored for almost two months and compared with data from the group that did not receive gene therapy. At the 80-day mark, when the injections were given, the average weight of the obese high-fat group was 20 percent greater than it had been at the beginning of the experiment. But 56 days after the injections, the average weight of the rats that received leptin gene therapy was only 3 percent greater than it was when the experiment began. Those that received the green fluorescent protein remained 20 percent heavier until the experiment's end. Among the animals fed standard rat chow, which initially gained weight but then leveled off, the average weight was about 10 percent heavier at the end of the experiment.
"(The results) supported our hypothesis that there is some kind of insufficiency of leptin in those sites that are the targets of leptin in normal conditions and in normal rats," Kalra said.
Next, UF researchers hope to learn how long the paraventricularnucleus produces leptin after gene therapy is administered, Kalra said. Because the procedure involves surgery, possible human applications are years away, but knowledge gained through the rat studies may lead to noninvasive methods of overcoming leptin resistance.
Leptin resistance intrigues scientists and affects up to 95 percent of dieters, said leptin expert Tamas Horvath, head of reproductive neuroscience at the Yale University School of Medicine's department of obstetrics, gynecology and reproductive sciences.
"I think it's difficult to predict what is the role of leptin resistance in our inability to lose weight in the initiation of a diet," Horvath said. "What we've been discovering in working with the hypothalamus in particular is the tremendous amount of plasticity going on during these endocrine metabolic events, so it's reasonable to assume that the wiring of the hypothalamus is affected by both leptin resistance as well as the diet, and that may add another level of complexity to this whole behavior paradigm."
There's no magic pill for easy weight loss, but exercise and good nutrition are as reliable as ever, he said. "It's important to emphasize both," he said.
Scientist's device to improve breathlessness is focus of innovative UF
By Sarah Carey
GAINESVILLE, Fla. - Are the Donald Trumps and Bill Gateses of the world born or bred? Leaders of an innovative University of Florida program that aims to train the entrepreneurs of the future bet it's both.
Housed in UF's College of Engineering, the Integrated Product and Process Design program, or IPPD, offers business and engineering students the opportunity to develop "real world" products while interacting with corporate partners.
Historically, IPPD projects have been industry-sponsored, involving concepts provided by such corporate heavy hitters as Dow Chemical, Dell Computer, IBM and Motorola. Now, for the first time, three UF inventions are the focus of 15 IPPD students, who are zeroing in on the inventions' marketing potential. UF also is unique in the way it has structured the multidisciplinary program, combining the perspectives of undergraduate engineering students and those of students working toward master's degrees in business.
These students are currently turning their attention to a device developed by Paul Davenport, Ph.D., a professor at UF's College of Veterinary Medicine, that can be used in conjunction with a training program to reduce vocal strain and strengthen voice muscles. It has already undergone extensive testing in high-risk performers in street and musical theater and choral ensembles, in Navy divers and even in high-school band students. Articles documenting the program's positive preliminary results have appeared in Advance for Speech-Language Pathologists & Audiologists and in the Journal of Voice.
"What we've developed is a noninvasive mechanical device that fits in the patient's pocket, about the size of a tennis ball," Davenport said. "Using our device and training program for only three to four weeks, people can increase their breathing force an average of about 50 percent."
Davenport said that although the device is not a cure for patients with lung disease, for some it could improve quality of life."We estimate that there are approximately 20 million people with airway dysfunction of some type that this could help," he said.
Davenport's research prompted IPPD program Director Keith Stanfill, Ph.D., P.E., to seek funding for the students to tackle entrepreneurial projects focused on actual product inventions, not just concepts. In one project, students are working to develop a small device that will wirelessly update a computer to monitor dairy cows' key health indicators, such as temperature, if the cow is burning too much fat, and distance the cows travel. In another, the students are developing a low-cost device and service for contaminated groundwater remediation monitoring and analysis.
The students are part of a virtual startup company formed around Davenport's invention with the help of faculty and industry mentors. Undergraduate engineering students focus on the technology and design concepts, while graduate-level business students create a business plan and conduct market research. There is even a "virtual CEO" - a representative from MRI Devices, a company based in Waukesha, Wis., that has offices in Gainesville. The firm donated $20,000 to sponsor the project.
"With their investment in the project, as well as providing technical and business-related resources, they're helping to ensure the project's success," Stanfill said. "In addition, the students are gaining some really valuable skills."
Alan Marder, UF's licensing officer in charge of marketing Davenport's invention, said the IPPD's new focus could provide UF with the opportunity to take a leading role in the creation of new businesses by using intellectual property it already owns.
"Some of the more aggressive students will have the chance to become founding stockholders," Marder said. "I think it's pretty exciting."