The Truth About the Hormone Leptin and Obesity

by Katherine Kam @ WebMD & Reviewed by Laura J. Martin, MD When scientists discovered leptin in 1994, excitement arose about its potential as a blockbuster weight loss treatment.  WebMD asked two experts on leptin to discuss how this hormone affects weight and appetite, as well as other aspects of health. Q: What is Leptin? A: "Leptin is not our obesity hormone. Leptin is our starvation hormone," says Robert H. Lustig, MD, professor of pediatrics at the University of California, San Francisco and a member of the Endocrine Society's Obesity Task Force. Leptin is a protein that's made in the fat cells, circulates in the bloodstream, and goes to the brain. "Leptin is the way your fat cells tell your brain that your energy thermostat is set right," Lustig says. "Leptin tells your brain that you have enough energy stored in your fat cells to engage in normal, relatively expensive metabolic processes," he says.  But when people diet, they eat less and their fat cells lose some fat, which then decreases the amount of leptin produced. Then several processes begin within the body to drive leptin levels back up. Q: How Does Leptin Affect Weight? A: If this thing works like a thermostat, an adipostat, why do we keep gaining weight?" Lustig says. The problem is that overweight people have large amounts of leptin, but their brains aren't getting the important signal to stop eating. "How come the brain doesn't get it? That phenomenon is called ‘leptin resistance,'" says Lustig, who has done research on the subject. Leptin resistance is similar to insulin resistance in type 2 diabetes, in which the pancreas produces large amounts of insulin, but the body doesn't respond to it properly. Leptin levels can keep going higher as people get fatter. "We all have a leptin floor; the problem is, we don't have a leptin ceiling," Lustig says. In leptin-resistant people, the reward system doesn't cue a person to stop eating when leptin levels rise, Lustig says. Q: What about leptin supplements? A: Because leptin is a digestible protein that doesn’t enter the bloodstream, it can’t be taken in supplement form, Richard Atkinson, MD, an endocrinologist, obesity expert, and clinical professor of pathology at Virginia Commonwealth University says. Rather than taking supplements that haven’t been fully proven to help, overweight people have other options to aid leptin functioning, experts say. Lustig advises them to reduce resistance to insulin (a hormone that controls blood sugar) and to bring down high levels of triglycerides (a blood lipid). “Insulin resistance generates leptin resistance. The practical advice is: Get your insulin down,” Lustig says. “How do you get insulin down? The best way is don’t let it go up. Sugar makes insulin go up. We are overdosed on sugar in this country. I think that if we got the sugar down, our insulin resistance would improve and that would help with the weight loss.” Reducing high triglyceride levels helps, too, Lustig says. Too much triglyceride interferes with leptin’s journey from the blood to the brain via a leptin transporter that allows the hormone into the brain.
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