New hope for obesity treatment
Gokce A Toruner, MD, PhD
Dr. Umut Ozcan, of Children’s Hospital Boston and Harvard Medical School may have found an obesity treatment that unlocks the fat-fighting promise of leptin, an appetite-suppressing hormone.
The leptin was once thought of as a potential obesity wonder drug, but the reality has proved more complex. Leptin is a signal released by fat cells that tells the brain when to stop eating, and initially it showed promise in treating obesity in mice. But now it is known that obese humans actually have high levels of leptin. Ozcan said most people who are obese develop leptin resistance, in which the brain stops responding to the hormone's message to stop eating during a phone interview with Reuters
For years, industry and academic laboratories have been searching for a drug to make people’s brains sensitive to leptin again, without success. In the new study published in Cell Metabolism, Ozcan’s group first showed that the brain cells of obese mice have increased stress in the endoplasmic reticulum (ER) — a structure within the cell where proteins are assembled, folded into their appropriate configurations, and dispatched to do jobs for the cell. In the presence of obesity, the ER is overwhelmed and can’t function properly. After showing that this stress blocks the leptin response, Ozcan's team set about trying re-sensitize the brain to leptin by reducing the ER stress.
Ozcan’s group tried two existing drugs -- 4-phenyl butyric acid or PBA, which treats cystic fibrosis, and tauroursodeoxycholic acid or TUDCA, which treats a liver disease. Both act as ER stress reducers.. Both 4-PBA and TUDCA are safe in humans and already FDA-approved for clinical use. When the researcher gave either of the two drugs to obese mice fed a high-fat diet, then injected them with leptin, they have seen significant weight loss in these mice.
“I think our study will bring new hope for the treatment for obesity,” says Ozcan, according to a press release by Children’s Hospital Boston.
The next step is to try the drugs in humans.