Do They Work for Obesity & Weight Loss?


Curious about leptin? Here are the facts behind some frequently asked questions.

Leptin is a hormone. Those are chemical messengers that help different body parts work together. Leptin sends a signal to your brain that helps you feel full and less interested in food. You may hear it called a satiety hormone. (Satiety means hunger feels satisfied). It also plays a role in how your body turns fat into energy.

You’ve always got leptin in your body. It’s mostly made by your fat cells. But your stomach releases some when you eat. It circulates in your bloodstream and travels to your brain.

And that’s where leptin delivers a very important message: We have enough fuel!

“When the brain says, ‘Oh, we have leptin!’ That tells me that we have fat, which tells me that we have energy reserves to do stuff,” says Wajahat Mehal, MD, PhD, director of the Yale Metabolic Health and Weight Loss Program. That “stuff,” Mehal says, could be any number of things from exercise to growth in puberty to conceiving a child.

Low levels of leptin, on the other hand, are part of the complex hormonal dance that makes you feel more hungry.

Leptin is an appetite suppressant. When everything works the right way, it helps you maintain a healthy weight by balancing the amount of food you eat with how much fat you have.

More specifically, high leptin levels tell your brain “your fat cells are full,” which makes you less hungry.

If you’ve ever been on a diet, you might have noticed that you get hungrier when you cut your calories or start to lose weight. That’s in part because typically your body automatically makes less leptin when you lose fat mass. Though, keep in mind that you never lose fat cells. They just get smaller.

But it’s not always about body fat. Simply fasting for several hours can cause your leptin levels to drop.

“If someone fasts for 8 to 10 hours, your total body fat won’t change much during that time, but the leptin will drop,” Yale’s Mehal says. “That’s another way of telling the body I’m in a relatively low-energy state because I haven’t eaten for 10 hours.”

Hunger is complex, says Rutuja Patel, DO, medical director for medical weight loss at the Northwestern Medicine Central DuPage Hospital. Hormones aren’t the only things that affect it. There are deep seated social and psychological issues that can change the cycle of hunger and satiety, she says: “Does the food look good to me? Do I really want to eat it? Do I have a circle of friends sitting here … so maybe I’ll eat a little more?”

Even your regular lifestyle habits of diet, exercise, and stress management can play a part.

Most humans have a “diurnal” rhythm to their day. That means they are active during the day and sleep at night. Leptin levels tend to peak between midnight and dawn, making you less hungry. That makes sense because there’s not much you can do about being hungry when you’re asleep in the middle of the night.

But sleep still plays a big part in leptin levels. A lack of shut-eye will disrupt all your hormones, including leptin.

It could make you feel hungrier because your brain sees lack of sleep as a loss of energy that needs to be replaced.

And the reverse may be true as well. Being very hungry at bedtime can cause lower leptin levels and that could interfere with your sleep. In fact, a lack of sleep can be a sign of starvation in people with a serious lack of body fat or daily calories.

Sometimes your brain tells you to eat more even when you have plenty of leptin and lots of fat cells. That’s called leptin resistance. Doctors don’t test for it regularly, but experts agree it’s common in people with obesity.

Think of leptin resistance like insulin resistance in type 2 diabetes. That’s when the pancreas makes a lot of insulin, but the body doesn’t respond to it. Leptin resistance “works exactly the same way,” Patel says, “where the (brain) receptors are resistant.”

Leptin resistance can lead to overeating and excess fat storage.

Other health problems can mess with your leptin signaling too. For example, chronic inflammation and high levels of triglycerides (a kind of fat found in your blood) can make it harder for leptin to cross the blood-brain barrier.

“Now you have a double whammy,” Patel says. “Not only do you have a little leptin resistance, but you also don’t have enough leptin going where it needs to go.”

Though there’s ongoing research on so-called “leptin sensitizers” to help improve response to leptin, there aren’t yet any drug therapies on the market.

But you can target insulin resistance, which often occurs alongside leptin resistance. Improve your sensitivity to insulin with medication, a healthy diet, plenty of exercise, and good sleep habits, and your leptin resistance may improve as well.

There was a lot of buzz around leptin when scientists first discovered it in the mid-1990s, says Dipali Sharma, PhD, a professor of oncology at Johns Hopkins University School of Medicine.

“Everybody thought: We’ve got a cure for obesity – people can be given leptin supplements and they’ll definitely lose weight,” Sharma says. “(But) over the years, they found that’s not the case.”

Scientists had good reason to think leptin might work as a weight loss tool. It all started with a mouse.

For decades scientists were curious as to why a certain breed of mouse kept overeating, laying around, and gaining weight. They eventually discovered the hormone leptin – and found that it played a big part in making mice feel hungry or full. This particular breed of weight-gaining mouse had a genetic anomaly that kept leptin levels low and hunger levels high.

Scientists thought people with obesity might be like that leptin-lacking mouse. But it turns out leptin deficiency is extremely rare in humans. So far, Sharma says, we only know of “maybe 100 people” in the world who make little or no leptin.

People with leptin deficiency are prone to obesity early in life. They need daily shots of a leptin-like protein to control their weight.

What happens if you give this same treatment to people who have the far more common condition of leptin resistance (see above question)?

Unfortunately, it doesn’t change a thing. Doctors continue to work on the problem.

Leptin isn’t a vitamin or mineral. You can’t absorb it from a pill. In fact, “leptin supplements” don’t contain any actual leptin. If they did, your stomach would simply digest them before they could have any effect on your body.

So what’s in them? All kinds of stuff.

Some contain caffeine, which may suppress your appetite. Others are just a mix of herbs and vitamins. They might not be harmful, but there’s no evidence they’ll have any effect on your leptin levels.

Ask your doctor before you take any supplements, especially if you also take prescription or over-the-counter medications.

Though scientists have just scratched the surface when it comes to leptin, they know it plays a part in various aspects of bodily health. That includes bone health, good immune function, and fertility.

“Anything the body needs to do is going to need energy,” Mehal says. “Each system is going to check the leptin levels before it does its thing.”

For example, if your leptin levels are too low, “the immune system won’t switch on fully,” Mehal says. “It’ll be like: What’s the point? The energy isn’t available for this.”

Healthy leptin levels can boost your chances of getting pregnant or carrying a child. It sends a signal to your brain that it’s OK to ovulate and prepare the uterus for a baby. This makes sense, because a body needs plenty of energy and nutrients to support the growth of a baby.

During pregnancy, leptin can help babies get the right nutrients to grow, Patel says. But in women who have obesity there may be problems with leptin signaling that interfere with this process.

Leptin gives a kind of green light signal to many other systems in the body. That includes your immune cells. A strong immune response is a good thing when you’re sick. But too much inflammation can cause health problems.

People who have obesity and high leptin often have chronic inflammation. That’s linked to heart issues, cardiovascular diseases, insulin resistance, and cancer.

In women, high leptin and obesity can boost the chances of breast cancer. Leptin-related inflammatory “cytokines” send signals that seem to impact how breast cancer cells grow and stay alive.

It’s important to note that not everyone with obesity will develop breast cancer. But in those who do, Sharma says, leptin can promote cancer growth and progression at every stage.

On top of that, women with obesity often don’t respond as well to hormonal breast cancer treatments when compared to those with lower body weights. New research shows that high leptin levels might be to blame.

Some studies in mice have found evidence that leptin can blunt the effects of a common estrogen-positive breast cancer drug.

Future drug therapies may target high leptin levels or leptin resistance. But for now, Sharma says, it’s best to aim for a healthy body mass index (BMI), especially during breast cancer treatment. Even a 5% to 10% weight reduction can be helpful in women who have a very high BMI, she says.

Work with your doctor to come up with a weight loss plan that works for you.


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