Leptin is a hormone that is produced by your body's fat cells. It is often referred to as the "satiety hormone" or the "starvation hormone." Leptin's primary target is in the brain — particularly an area called the hypothalamus. Leptin is supposed to tell your brain that — when you have enough fat stored — you don't need to eat and can burn calories at a normal rate.

However, leptin's main role is long-term regulation of energy, as well as how much fat you store in your body.

The leptin system evolved to keep humans from starving or overeating both of which would have made you less likely to survive in the natural environment. But in today's society something is broken in the mechanism that is supposed to prevent us from overeating. The more body fat they carry, the more leptin they produce.

The fat cells use leptin to tell your brain how much body fat they carry. High levels of leptin tell your brain that you have plenty of fat stored, while low levels tell your brain that fat stores are low and that you need to eat.When you eat, your body fat goes up, leading your leptin levels to go up. Thus, you eat less. Conversely, when you don’t eat, your body fat goes down, leading your leptin levels to drop. At that point, you eat more and burn less.

Leptin Resistance

People who are obese have a lot of body fat in their fat cells. Because fat cells produce leptin in proportion to their size, people who are obese also have very high levels of leptin.

Given the way leptin is supposed to work, many obese people should naturally limit their food intake. In other words, their brains should know that they have plenty of energy stored. However, their leptin signaling may not work. While copious leptin may be present, the brain doesn't see it. This condition — known as leptin resistance — is now believed to be one of the main biological contributors to obesity. When your brain doesn't receive the leptin signal, it erroneously thinks that your body is starving — even though it has more than enough energy stored.

Your brain then encourages:

Thus, eating more and exercising less is not the cause of weight gain but rather a possible consequence of leptin resistance, a hormonal defect. For most people who struggle with leptin resistance, willing yourself to overcome the leptin-driven starvation signal is next to impossible. This is also main reason why so many people lose a significant amount of weight only to gain it back shortly thereafter.

Reasons of Leptin Resistance

Several potential mechanisms behind leptin resistance have been identified.

These includes

Fixing Leptin Resistance

There are several things you can do:


Ghrelin, the appetite increaser, is released primarily in the stomach and is thought to signal hunger to the brain. You'd expect the body to increase ghrelin if a person is undereating and decrease it if he or she is overeating.

German researchers have suggested that ghrelin levels play a big role in determining how quickly hunger comes back after we eat. Normally, ghrelin levels go up dramatically before you eat; this signals hunger. They then go down for about three hours after the meal.

But some researchers believe that ghrelin is not as important in determining appetite as once thought. They think that its role in regulating body weight may actually be a more complex process.

Neuropeptide Y

Neuropeptide Y, or NPY, is the most abundant peptide in the central nervous system. Found mostly in the hypothalamus, it acts as a hormone and neurotransmitter. It’s involved in a host of actions locally in the brain and throughout the body.

Most importantly for the present purposes, NPY is considered the most potent appetite-stimulating compound in the human body. Each of the other hormones discussed in this post regulates food intake by acting on NPY in the hypothalamus. For example, ghrelin increases NPY activity, while leptin suppresses it. Elevated NPY strongly increases the drive to eat, especially carbohydrates.

NPY acts to maintain energy homeostasis by decreasing energy expenditure, movement, sex drive, and thermogenesis when needed. It’s also expressed by fat cells, and research suggests that NPY promotes fat storage.

Peptide YY

Peptide YY (PYY) is produced in the intestines after you eat. It travels through the bloodstream to the hypothalamus, where it inhibits NPY, decreasing appetite. PYY also modulates other digestive functions, including pancreatic and gallbladder activity.

The amount of PYY produced is proportional to the number of calories consumed. Studies find that higher-protein meals cause the greatest rise in PYY, followed by higher-fat meals. Not only do high-carb meals stimulate the least PYY, PYY peaks and then starts to decrease quickly after high-carb meals, whereas it continues to rise for hours after meals containing more fat and protein. This may be one reason you don’t stay full for long after eating high-carb meals.


Cholecystokinin (CCK) was the first known satiety hormone. It is secreted in the gastrointestinal tract, especially in the small intestine. CCK rises quickly after eating, especially in response to fat and protein in the meal, and it triggers the initial release of PYY.

Like PYY, CCK is involved in various processes related to digestion, especially the digestion of fat. CCK also has interesting effects in the brain. The hippocampus contains a large concentration of CCK receptors, indicating that CCK plays an important role in learning and memory, though it’s still not well understood. High levels of CCK are related to anxiety and panic attacks, while schizophrenic patients may have abnormally low levels of CCK in their brains.

Glucagon-like Peptide-1

Abbreviated GLP-1, this hormone is secreted by the ileum and colon in response to nutrient intake. It acts as a satiety hormone, but researchers are especially interested in how it stimulates insulin secretion, improves insulin sensitivity, and helps regulate blood glucose. GLP-1 figures prominently in experimental treatments for type 2 diabetes.

Following bariatric surgery, patients’ GLP-1 and PYY increase significantly, which probably accounts for post-surgical reductions in appetite, which can persist for decades after the procedure. Research using a rat model also suggests that GLP-1 facilitates the rapid metabolic improvements that often follow surgery.


Let’s end with a familiar one. You probably know that the pancreas releases insulin after you eat, especially following carbohydrate intake. Insulin is sometimes called the “storage hormone” because one of its main jobs is to “unlock” adipose cells in order to store fat for future use. In healthy individuals, it also supports energy homeostasis by inhibiting lipolysis (fat burning) when there is sufficient glucose in the bloodstream to supply energy.

As with the other hormones discussed here, insulin also acts as an energy barometer for the brain. It crosses the blood-brain barrier, where it regulates NPY expression and suppresses appetite.

Furthermore, in human studies, hormone levels don’t consistently map on to our actual eating behavior as you’d expect. This might be because scientists haven’t uncovered the whole picture and don’t understand how all the various pieces work together to produce hunger. Probably, it’s also because we humans are complicated creatures who eat for a lot of reasons other than pure physiological hunger.

What does it all mean? I think it means don’t look for a magic pill that will allow you to control appetite and hunger. If you struggle with unwanted hunger, the first thing to ask is whether you are eating enough to meet your energy needs. Are sending your brain scarcity signals by not eating enough, or perhaps not often enough? That’s an easy fix.

Next, you can try manipulating your macros. One of the advantages of low-carb, high-fat (LCHF) diets over low-fat, high-carb (LFHC) diets is that appetite is managed much better on LCHF. Protein is also quite satiating, likely due to the actions of hormones like ghrelin and PYY. If you go very low-carb, you might experience the appetite suppressing effects of ketosis as well.

Check in with your stress levels and sleep habits. Too much of the former and not enough of the latter can drive up appetite.

If none of those is the answer, it might be time to make an appointment with an endocrinologist or functional medicine practitioner who can help you dig deeper.

Hunger isn’t something to be avoided, though. Hunger and satiety are normal physiological signals. Their job is to keep us alive and thriving. Rather than trying to manipulate or hack hunger, it’s useful to understand where it comes from so that we can respond appropriately and have the energy we need to be active and healthy.

Key Takeaways

Further reading