In the study, 24 middle-aged male rats 22 months old were divided into four groups. One was a control group that received no injection, and another was a control group that received the solution without the therapeutic genes. A third group was injected with a solution containing the gene that controls POMC production, and the remaining group was given a solution containing a gene that produces a fluorescent protein with no therapeutic effect. The genes were delivered through the solution using a form of the apparently harmless adeno-associated virus.
In the three injected groups the solution was delivered into a specific region of the hypothalamus, a primitive part of the brain that controls many basic body functions. The rats that received the solution without any genes and the rats that received the fluorescent protein showed similar, temporary decreases in food intake and weight compared with the group that received no injection. These results suggested the procedure used to deliver the solution had a temporary effect on body weight regulation, Scarpace said.
The six rats that received the POMC gene steadily lost weight and 42 days after the injection were 19 percent lighter overall than those in the group that received the fluorescent protein. Those that received the POMC gene showed a substantial - though temporary - decrease in food consumption, and two measurements related to diabetes, glucose metabolism and insulin sensitivity, improved 19 percent compared with rats in the fluorescent protein group.
UF researchers plan to investigate over the next one to two years the long-term effects of the gene therapy on rats with diet-induced obesity as well as other animals with age-related obesity, Scarpace said.
Scarpace ™s research suggests that age-related obesity actually may be caused by POMC deficiency rather than leptin resistance, said obesity researcher Charles V. Mobbs, an associate professor with the Mount Sinai School of Medicine in New York City.
The fact that he ™s been able to show that POMC replacement in fact can reduce obesity in older animals strongly supports the hypothesis that POMC itself may be the problem, rather than leptin, Mobbs said.
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