It's been called the "obesity hormone" or "fat hormone" -- but also the "starvation hormone." When scientists discovered leptin in 1994, excitement arose about its potential as a blockbuster weight loss treatment. Even today, the Internet is loaded with sites that sell leptin supplements. Any truth to those pitches? And what exactly is leptin?
ishonest 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?
"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. "In other words, when leptin levels are at a certain threshold -- for each person, it's probably genetically set -- when your leptin level is above that threshold, your brain senses that you have energy sufficiency, which means you can burn energy at a normal rate, eat food at a normal amount, engage in exercise at a normal rate, and you can engage in expensive processes, like puberty and pregnancy".
But when people diet, they eat less and their fat cells lose some fat, which then decreases the amount of leptin produced.
"Let's say you starve, let's say you have decreased energy intake, let's say you lose weight," Lustig says. "Now your leptin level goes below your personal leptin threshold. When it does that, your brain senses starvation. That can occur at any leptin level, depending on what your leptin threshold is."
"Your brain senses that and says, ‘Hey, I don't have the energy onboard that I used to. I am now in a starvation state,'" Lustig says.
Then several processes begin within the body to drive leptin levels back up. One includes stimulation of the vagus nerve, which runs between the brain and the abdomen.
"The vagus nerve is your energy storage nerve," Lustig says. "Now the vagus nerve is turned on, so you get hungrier. Every single thing the vagus nerve does…[is] designed to make you take up extra energy and store it in your fat. Why? To generate more leptin so that your leptin can re-establish its personal leptin threshold... It causes you to eat and it causes you to get your leptin back to where it belongs."
Q. How does leptin affect weight
"Here's the question: 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 resistance, your leptin is high, which means you're fat, but your brain can't see it. In other words, your brain is starved, while your body is obese. And that's what obesity is: it's brain starvation."
Not only is leptin part of the hunger system, it's also part of the reward system, Lustig says. "When your leptin levels are low, food is even more rewarding. When your leptin levels are high, that's supposed to extinguish the reward system so that you don't need to eat so much, and food doesn't look nearly as good."
But in leptin-resistant people, the reward system doesn't cue a person to stop eating when leptin levels rise, Lustig says. "The leptin is being made by the fat cells, the fat cells are trying to tell the brain, ‘Hey, I don't need to eat so much,' but the brain can't get the signal. You feel hungrier and the reward doesn't get extinguished. It only gets fostered, and so you eat more and you keep going and it becomes a vicious cycle. If your brain can't see the leptin signal, you're going to get obese."
Q. Can leptin work as an obesity treatment?
That was the great hope after leptin's discovery in 1994, says Richard Atkinson, MD, an endocrinologist, obesity expert, and clinical professor of pathology at Virginia Commonwealth University.
Q. What about leptin supplements, such as those sold on the Internet?
Because leptin is a digestible protein that doesn’t enter the bloodstream, it can’t be taken in supplement form, Atkinson says. “If you were to take it as a pill, it’s just like eating chicken or beef. It’s a protein and your body would just break it up, so you wouldn’t absorb it from a pill.”
Q. Does leptin affect other parts of the body?
Leptin appears to have many functions that scientists are still exploring. "It didn't work as a weight loss agent, but there's now starting to be some other things that are really interesting about it," Atkinson says.
The hormone plays a role in heart and bone health, Lustig says. "We know that leptin is very important in keeping the immune system happy and that chronic inflammation occurs in the face of inadequate leptin signaling, and that's part of cardiovascular disease."
"We also know that leptin has direct effects on bone to increase bone health and bone mineral density, so when your leptin's working right, your bones are healthier and they accrue more calcium," he says.
Scientists are also finding some associations between leptin and certain cancers, Atkinson says. For example, some recent research suggests that leptin can promote the growth of melanoma, a type of skin cancer.
According to Atkinson, leptin may even affect women's fertility. "If the brain doesn't sense leptin, you won't be fertile. If you think back to our caveman days, when there were lots of famines, if you didn't have enough fat to survive a pregnancy, then you're better off not getting pregnant in the first place. Some people have thought that the leptin feeds back on the hypothalamus to keep the reproductive hormones working well, too."