January 7, 2009

Fat-zapper leptin may work after all

The potential of the appetite suppressing hormone -- leptin -- may be realized after all, U.S. researchers say.

The discovery of leptin, an appetite-suppressing hormone secreted by fat tissue, created great hopes for an effective treatment for obesity, but it was found the obese are unresponsive to leptin due to leptin resistance in the brain.

The study, published in Cell Metabolism, found two chaperones -- 4-PBA or TUDCA -- increase leptin sensitivity as much as 10-fold and resulted in significant weight loss in mice.

Without the chaperones to help fold and block proteins, the brain cells of obese mice show increased stress in the endoplasmic reticulum -- 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 endoplasmic reticulum is overwhelmed and can't function properly.

Most humans who are obese have leptin resistance. Leptin goes to the brain and knocks on the door, but inside, the person is deaf, study researcher Dr. Umut Ozcan of Children's Hospital Boston said in a statement. I think our study will bring new hope for the treatment for obesity.

The two chaperones used in the study are already approved by the U.S. Food and Drug Administration for clinical use.