Professor Kim Janda
Many frustrated dieters repeat the same story: they went on a diet, lost weight, then went off the diet-regimen only to gain back the weight and sometimes more. Experts call this “yo-yo dieting,” and explain that it is caused by the body’s hormonal response. When you diet, the body responds as if it were starving and produces gastric hormones to slow down fat metabolism and stimulate eating. When you come off the diet, however, your body’s metabolism often maintains this slow speed, storing energy in the form of fat and causing you to gain weight.
Many believe that this metabolic cycle is an evolutionary response to the feast or famine conditions of early humans – those who were genetically predisposed to eat heartily and store fat efficiently during periods of plenty were more likely to survive the next round of scarcity. In recent years, however, that powerful genetic legacy has come in direct conflict with the dangerous phenomenon of overeating in the developed world.
Seeing obesity take its grip on Americans, Associate Professor Eric Zorrilla and Kim Janda, who is Ely R. Callaway, Jr. Professor of Chemistry at Scripps Research, a member of the Skaggs Institute for Chemical Biology, and director of the Worm Institute of Research and Medicine, turned their attention to the chemical processes involved in weight loss and gain. Their initial focus has been on ghrelin, a naturally occurring hormone that helps regulate energy balance in the body. During periods of weight loss such as dieting, the body produces high levels of ghrelin to slow down fat metabolism, encourage eating, and promote fat retention.
In 2006, the team published a study looking at the effect of vaccines that kept ghrelin away from the brain and central nervous system – where it takes effect. They found that animal models that “received the most effective vaccines didn’t eat differently than the others, including the control models,” explained Zorrilla. “That makes our findings exciting therapeutically – the vaccine slows the rate of weight gain, while still allowing for normal eating habits…This vaccine may have the real potential to prevent or seriously reduce yo-yo dieting because it interferes with ghrelin’s ability to produce weight gain and fat accumulation.”
Janda’s and Zorrilla’s findings may mark a turning point in the treatment of obesity by confirming the effectiveness of immunopharmacothrapy to combat weight gain. Immunopharmacotherapy engages the immune system, specifically antibodies, to bind to selected targets, directing the body’s own immune response against them. Janda explains that they turned to immunopharmacotherapy vaccines because other methods had proven remarkably unsuccessful. “They are effective only while treatment is maintained and when treatment stops, weight returns,” he says. “For obesity treatments to work, they must affect energy intake, absorption, expenditure, or storage. Our vaccine works by changing expenditure or storage.”
Last fall, team members took their work to the next step when they discovered a catalytic antibody that degrades ghrelin. “These findings not only validate antibody-based therapeutics,” Janda explains, “but strongly suggest that catalytic anti-ghrelin antibodies might help patients reach and maintain their weight loss goals.”
Questions remain, though. Not only could there be more effective ghrelin antibodies, but scientists need to better understand the effect of the antibodies over the long term and their impact on individuals with varying body weights.
As Zorrilla and Janda take their work closer to clinical application, your support can make the difference by ensuring these scientists have the resources and the freedom to pursue critical lines of inquiry.