The discovery more than a decade ago of leptin, an appetite-suppressing hormone secreted by fat tissue, generated headlines and great hopes for an effective treatment for obesity. But hopes dimmed when it was found that obese people are unresponsive to leptin due to development of leptin resistance in the brain. Now, researchers at Children’s Hospital Boston report the first agents demonstrated to sensitize the brain to leptin: oral drugs that are already FDA-approved and known to be safe. Findings were published January 7 by the journal Cell Metabolism.
In 1995, researchers reported in Science that they had isolated a protein that is present in normal mice, but not in an obese strain of mice called ob/ob, which lacked a gene also called ob. When either obese or normal mice were directly injected with the protein now called leptin they ate less and lost weight.
“Everyone in the field thought they would get the Nobel,” says Umut Ozcan, MD, of Children’s Division of Endocrinology. Unfortunately, when obese humans took the hormone, they lost weight only temporarily then rebounded back. “Most humans who are obese have leptin resistance,” says Ozcan. “Leptin goes to the brain and knocks on the door, but inside, the person is deaf.”
For years, industry and academic laboratories have been searching for a drug to make peoples’ brains sensitive to leptin again, without success.
In the new study, Ozcan’s group first showed that the brain…