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Do they work for obesity and weight loss?


Interested in leptin? Here are the facts behind some frequently asked questions.

What is leptin?

Leptin is a hormone. They are chemical messengers that help different parts of the body 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 converts fat into energy.

You still have leptin in your body. It is mainly made by your fat cells. But your stomach releases it when you eat. It travels through your bloodstream and into your brain.

And this is where leptin delivers a very important message: we have enough fuel!

“When the brain says, ‘Oh, we have leptin!’ It tells me we have fat, which tells me we have energy reserves to do things,” 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 puberty growth to conceiving a child.

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

How does leptin work?

Leptin is an appetite suppressant. When everything is working properly, it helps you maintain a healthy weight by balancing the amount of food you eat with the amount of fat you have.

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

If you’ve ever dieted, you may have noticed that you feel hungrier when you cut calories or start losing weight. This is partly because your body automatically produces less leptin when you lose body fat. However, 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 leptin will go down,” says Yale’s Mehal. “It’s another way of telling the body that I’m in a relatively low energy state because I haven’t eaten in 10 hours.”

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

Even your usual lifestyle habits around diet, exercise, and stress management can play a role.

How Does Sleep Affect Leptin Levels?

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

But sleep still plays an important role in leptin levels. A lack of sleep will disrupt all of your hormones, including leptin.

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

And the reverse can also be true. Being very hungry at bedtime can cause leptin levels to drop and it could interfere with your sleep. In fact, lack of sleep can be a sign of starvation in people with a severe lack of body fat or daily calories.

What is leptin resistance?

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

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

Leptin resistance can lead to overeating and excessive fat storage.

Other health conditions can also disrupt your leptin signaling. For example, chronic inflammation and high levels of triglycerides (a type of fat found in your blood) can make it harder for leptin to cross the blood-brain barrier.

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

Although there is ongoing research into so-called “leptin sensitizers” to help improve leptin response, there are no drug therapies on the market yet.

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

Are some people leptin deficient?

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

“Everyone was thinking: we have a cure for obesity – people can get leptin supplements and they will definitely lose weight,” Sharma says. “(But) over the years they’ve found out that’s not the case.”

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

For decades, scientists have been curious as to why a certain breed of mouse kept overeating, lying down and gaining weight. They eventually discovered the hormone leptin – and found that it played an important role in making mice feel hungry or full. This particular breed of mice that gained weight had a genetic abnormality that kept leptin levels low and hunger levels high.

Scientists thought obese people might look like this leptin-depleted mouse. But it turns out that 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 doses of a leptin-like protein to control their weight.

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

Unfortunately, that doesn’t change anything. Doctors continue to work on the problem.

What about over-the-counter “leptin supplements”?

Leptin is not a vitamin or mineral. You cannot take it from a pill. In fact, “leptin supplements” do not contain real leptin. If they did, your stomach would simply digest them before they could have any effect on your body.

So what’s in it? All sorts of things.

Some contain caffeine, which can suppress your appetite. Others are just a mixture of herbs and vitamins. They may not be harmful, but there is no evidence that they have any effect on your leptin levels.

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

What else does leptin do?

Although scientists have only scratched the surface when it comes to leptin, they do know that it plays a role in various aspects of bodily health. This includes bone health, good immune function and fertility.

“Everything the body needs to do is going to need energy,” Mehal says. “Each system will check leptin levels before doing its job.”

For example, if your leptin levels are too low, “the immune system won’t fully activate,” says Mehal. “It will be like: what’s the point? The energy is not available for this.

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

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

Is there a link between leptin, cancer and inflammation?

Leptin gives a sort of green light signal to many other body systems. This 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 are obese and high in leptin often have chronic inflammation. This is linked to heart problems, cardiovascular disease, insulin resistance and cancer.

In women, high leptin and obesity can increase the risk of breast cancer. Leptin-linked inflammatory “cytokines” send signals that appear to impact the growth and survival of breast cancer cells.

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

Additionally, obese women often do not respond as well to hormone treatments for breast cancer as those with lower body weight. New research shows that high leptin levels could be to blame.

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

Future drug therapies could target elevated 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 percent weight reduction can be helpful in women who have a very high BMI, she says.

Work with your doctor to develop a weight loss plan that’s right for you.


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