Leptin and Weight Loss

Leptin is one of nature’s appetite suppressants. 

When it’s functioning properly, it tells your brain to stop eating when you’ve had enough. It’s the “put down your fork” hormone that helps regulate energy storage and expenditure - and it’s made by your fat cells.

Unlike ghrelin, which is made and released by the stomach in response to food intake, leptin is secreted at night, like melatonin.

It works over the long term by moving through the bloodstream to the brain, specifically the hypothalamus and hippocampus, telling it to decrease hunger signals and increase energy utilization - which is fantastic if you’re trying to lose fat!

But more leptin isn’t necessarily better. In fact, when your brain is bombarded with leptin signals from your fat cells, over time it becomes desensitized to the satiety signal.

The receptors for leptin in the brain become numb or less responsive to the increased leptin levels, which means you don’t feel full even when you are.

It’s like you have a broken hunger thermostat, where even though the temperature is turned all the way down, the furnace keeps kicking out heat.

In this case, it can cause intense cravings especially for carbs and sugars, addictive eating patterns, and increased fat gain or trouble maintaining a healthy body composition.

This is called Leptin resistance, and it is a vicious cycle that many people find themselves trapped in.

Because not only does leptin resistance trigger cravings and hunger signals, it also changes your metabolism so you burn less stored energy or fuel.

This means the food you eat is more likely to be stored as fat…which then releases MORE leptin, which increases Leptin resistance and leads to more hunger and cravings.

By contrast, when you have appropriate levels of leptin, and your receptors are getting the signal in your brain, leptin keeps your food consumption balanced with your energy needs.

People with PCOS often have leptin resistance - as do people who still never feel full even when in ketosis.

A few years ago I worked with a patient who was told by a health coach that in order to overcome her weight loss resistance and lose body fat, she simply needed to listen to her body’s signals and eat when she felt hungry - and stop when she felt full.

I’m sure you can imagine how frustrating and confusing that advice is when you have leptin resistance!

It’s important to note that insulin resistance, which is another instance of poor receptivity to a regulatory hormone, often begins the process of becoming leptin resistant by causing higher body fat percentages, chronic inflammation, and initiating that downward spiral of cravings and weight gain.

Elevated triglycerides, another hallmark of insulin resistance, can also interfere with leptin’s ability to signal to the brain, which disrupts appropriate satiety or fullness.

And leptin doesn’t only regulate hunger - it also modulates your immune system, which is in charge of chronic inflammation.

Leptin problems can accelerate the breakdown of cartilage and joint tissue, and it is correlated with rheumatoid and osteoarthritis.

And healthy Leptin hormone signaling is also important for bone and reproductive health.

How do you know for sure if you have leptin resistance?

Well, you can measure fasting leptin in your blood, which will give you an idea of your levels.

“Normal” levels may vary depending on age, gender, and other factors, and they do increase over the course of the day - remember, leptin is like melatonin and follows a circadian rhythm in this way, so you’ll want to test this level in the morning before you’ve had anything to eat.

My optimal fasting range is less than 15ng/dL but some functional docs like to see less than 8 - much lower than the 20 or 30 you might see on a standard blood lab.

If you’re curious about your leptin levels, you may be able to order your own blood test via my website! You can learn more HERE.

Another way to test for leptin resistance is to check markers like fasting insulin, hemoglobin A1C, and triglycerides. These markers can give you a sense of how well your body is managing your blood sugars, which play a big role in triggering leptin resistance.

So, now that we understand how leptin works and how to test it, let’s talk about Functional Medicine strategies you can use to improve your leptin sensitivity, decrease cravings, boost your metabolism and lose fat!

Remember that leptin is secreted in a pulsatile pattern, like melatonin, at night? This means that maintaining a healthy circadian rhythm and getting enough quality sleep are super important for supporting healthy leptin levels and sensitivity of leptin receptors.

Research shows a strong link between weight gain, lack of sleep, and insulin resistance, which can all lead to leptin resistance.

If you’re getting less than 7-9 hours of sleep, you’re setting yourself up for leptin problems.

In one study, women who got six hours of sleep per night were 12% more likely to gain at least 30 pounds in 16 years compared to the women who slept seven hours per night. And women who got only five hours per night were 28% more likely to gain at least 30 pounds during that same period.

What are some things that can interfere with healthy sleep?

Caffeine, alcohol, and sugar can all throw off your circadian rhythm.

Evening exposure to blue light from your phone, computer, or TV screen can also disrupt your sleep cycle.

Consider a mug of chamomile tea instead of that glass of wine to unwind in the evening, and pick up a pair of stylish blue-light blocking glasses for your nightly episode - or better yet, read a book before bed!

If you practice great sleep hygiene and still struggle to fall asleep or stay asleep, it may be time to take a deeper look at hormones like cortisol, estrogen, progesterone, and melatonin.

Cortisol and chronic stress can also lead to leptin resistance, so learning how to create stress resilience is key to curbing cravings and promoting fat loss. 

Not only does stress cause cravings by affecting leptin, it also lowers your mental energy and planning ability, making it more difficult to make healthy, goal-oriented decisions around food.

It can also lead us to use food as comfort, meaning that we gravitate toward endorphin-releasing foods that are mostly low-quality and have poor nutrient density.

Not getting enough quality sleep can lead to this same kind of dietary indiscretion, which in itself can cause fat gain.

If you’re looking for a comprehensive guide to understanding cortisol and implementing meaningful resilience-building strategies, check out my Stress Smarter Mini Workshop.  You can learn more about it HERE.

Given the link between insulin resistance and leptin resistance, it’s probably no surprise that eating too much sugar can also cause cravings and leptin dysfunction.

But some studies suggest that this is also true for fructose, a type of sugar found in fruit. When you overeat fructose, it raises your leptin excessively.

Does this mean you should avoid eating fruit?

Absolutely not - but it is smart to be careful about overconsumption, which depends on many individual factors including your genetics, how much you exercise, what else you’re eating (or overeating), and the function of your metabolism.

It’s important to note that there’s a difference in how your body responds to fructose from a can of soda vs. a handful of blueberries, which has tons of healthy fiber and micronutrients.

So if you’re struggling with leptin resistance, my suggestion is to keep your fructose consumption to less than 20 grams per day - and avoid liquid sugar sources like fruit juice, soda, sports drinks, and sweetened coffee drinks.

It may also be helpful to limit high-glycemic fruits like pineapple and other tropical fruits as well as dried fruits, and focus on low-glycemic fruits like dark berries, apples, and pomegranates.

Exercise, especially high-intensity interval training, is a non-dietary strategy for curbing cravings and losing fat.

Studies show that for some women, exercise helps lower leptin levels, which in the case of leptin resistance is a good thing.

Maintaining healthy muscle mass, especially after 40, is a great way to drive metabolic function as well.

And as an added bonus, exercise helps women maintain healthy testosterone levels, which in turn also help keep metabolism healthy.

AND, moving your body every day is a great way to improve sleep, which improves leptin levels, too.

I’ve found that many women love to take walks, but don’t focus enough on building and maintaining muscle, which means they miss out on this leptin-improving strategy.

If you’ve dialed in your food choices, you’ve incorporated healthy exercise, and you’re still battling cravings or never feel full, there are some nutraceuticals that can be helpful as well.

Berberine, a natural compound found in plants, is sometimes called “nature’s ozempic” for it’s ability to improve insulin resistance, balance blood sugar, and help folks lose fat.

According to a 2012 meta-analysis of 14 different studies including more than 1,000 people, berberine was able to help with blood sugar control as much as the common diabetes medication metformin - and with far fewer side effects.

Because leptin resistance is so closely linked with insulin resistance and metabolic syndrome, Berberine helps calm cravings and improve metabolism, too.

Speaking of Ozempic, boosting your body’s natural production of Glucagon-like peptide 1, or GLP-1, can also have a profound impact on satiety.

When you eat, the GLP-1 hormone sends a signal to your pancreas that causes the release of insulin, which tells your cells to take in glucose from your blood, helping to lower your blood sugar.

GLP-1 hormone can also help lower appetite and food cravings by activating similar areas of your brain as leptin.

Just to be clear, I’m not saying that you need to take GLP-1 agonist drugs to get the benefits of this hormone - but you may need to enhance it’s production, especially if you’ve been metabolically dysfunctional for awhile, have too much body fat, or you have pre-diabetes or type 2 diabetes.

My favorite way to support your own body’s GLP-1 production is with a very special microbe called Akkermancia muciniphila.

Akkermansia not only produces butyrate, which boosts GLP-1, but it also helps balance blood sugar, which improves insulin sensitivity. AND best of all, it maintains the tight junctions between your intestinal cells, reversing intestinal hyper-permeability sometimes called leaky gut, which is a trigger for everything from depression to eczema to multiple sclerosis.

If you’re curious about Berberine or Akkermansia, and you’d like more details about dosing or which products actually work and meet third-party testing standards, check out my functional fat loss trio checklist - you can sign up for your copy of the info-packed PDF HERE. You’ll also find a link to purchase my preferred nutraceuticals for a really nice discount, so be sure to check that out.