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Researchers Control Hunger Hormone, Stopping Obesity in Mice

While investigators say these findings look highly promising at this stage, much more research is required to determine if this approach will succeed in humans

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ROCHESTER, Minn. - Mayo Clinic scientists have shown that injections of a hunger hormone blocker in mice can halt the typical weight gain after dieting and help prevent rebound obesity in the long term. The research findings appear in the Proceedings of the National Academy of Sciences.

“We think this approach—combined reduction of calories and hormone—may be a highly successful strategy for long-term weight control,” says W. Stephen Brimijoin, PhD, a Mayo Clinic molecular pharmacologist and senior author of the article. “Given the growing obesity crisis worldwide, we are working hard to validate our findings for medical intervention.”

The research was designed to mimic the circumstance of persons with obesity who manage to lose significant weight but then rebound because this triggers a rise in ghrelin, a key hunger hormone." It’s as if you’ve scored a touchdown but your body changes rules in midgame. Few individuals can maintain their weight loss because the dramatic metabolic impact releases irresistible cravings for food. In other words, help is desperately needed.

Help that proved successful in this study came from gene transfer of an enzyme called butyrylcholinesterase. The researchers loaded its DNA code into a neutralized virus, aiming at the appetite-driving hormone, ghrelin. The result was substantial and long-acting. Compared to controls, the rise in butyrylcholinesterase lowered the levels of active acyl-ghrelin and guided the mice toward normal eating habits. In fact, just a single treatment with the enzyme kept the mice at normal weights for the rest of their lives. Researchers expect the effects to correlate positively with reduction in ailments such as diabetes, metabolic syndrome and fatty liver disease.

While investigators say these findings look highly promising at this stage, much more research is required to determine if this approach will succeed in humans.

Co-collaborators—all of Mayo Clinic—are:

  • Ping Chen, PhD, first author
  • Yang Gao
  • Liyi Geng, PhD

The research was funded by the Minnesota Partnership for Biotechnology and Medical Genomics, Mayo Clinic, and the National Institute on Drug Abuse.

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