How Hormones Control your Appetite: The Story of Leptin and Ghrelin

In today’s environment we have constant access to highly processed foods loaded in sugar and low in fiber. In contrast, our ancestors had to search for unprocessed food and face the real threat of starvation on a regular basis. Our genes have evolved to support life in this type of austere environment and our metabolic system is not well adapted to ready access to highly palatable sugary foods night and day.

Specialized cells deep within your brain, in an area called the hypothalamus, control your eating. The hypothalamus secretes several different hormones and can be considered the control center for your body. Inputs to your hypothalamus come from electrical signals generated from your nerves as well as chemical signals carried through the blood by hormones. How does your hypothalamus control your eating? Nerves send electrical signals to your brain when your stomach is full of food. Ghrelin, the “hunger hormone”, is produced and released by the stomach when it is empty. Ghrelin stimulates appetite, increases food intake and promotes fat storage in the body.

Leptin, the “satiety hormone”, is released by fat cells in the body and is sent to the hypothalamus via the blood. It promotes satiety and also tells your brain how much body fat is currently stored. The vast majority of your body’s energy stores are in fat cells. Leptin levels are known to decrease when calories are restricted, which explains why it can be difficult to feel satiety when dieting.

Although obese individuals have higher leptin levels due to higher body fat percentage, they often have leptin resistance meaning that their bodies are resistant to the satiety- promoting effects of this hormone. Similar to the problem of insulin resistance, obese people typically have high levels of dysfunctional leptin which fails to control hunger and modulate weight appropriately.

To recap, your hypothalamus responds to blood levels of the hunger hormone ghrelin from the stomach, the satiety hormone leptin from the fat cells and insulin levels from the pancreas. The brain also directly monitors blood levels of glucose and fat.

It is important to appreciate the difference between “being hungry“ and “wanting to eat “. The sensation of hunger is under hormonal control and is not tied to a specific food. In contrast, the brain’s pleasure center in the nucleus accumbens releases dopamine which causes craving for a specific desired food such as cake or ice cream. Unfortunately, the leptin resistance that develops with obesity actually makes it more difficult for you to resist pleasurable foods that are associated with dopamine release in the brain.

The most powerful food cue for many is time of day. For example, if you eat lunch at a certain time of day, your brain will prepare to digest food at this time and it will stimulate insulin release before you even eat food. The insulin will cause glucose and fat levels to decrease in the blood and you will feel hungry. This time dependent hunger sensation is independent of the size of the previous meal.

Let’s go through a typical day for a person of normal weight without insulin resistance.

When you wake up in the morning, your stomach is empty and it releases the hunger hormone ghrelin which is sent to the hypothalamus in the brain. Your insulin levels are low because you have not consumed food overnight. You start feeling hungry.
You consume food and your stomach begins to fill up and become distended. Nerves from the digestive system relay this information to the brain. Your fat cells start releasing leptin and you feel full.
You don’t eat any snacks in the morning and you start to feel hungry at your customary lunch time of 12:30 PM. Your brain’s internal clock detects the time when you typically eat lunch and it prepares your digestive system to digest the upcoming meal. Insulin is released and your blood glucose and fat levels drop and you feel hungry.
You eat lunch and your leptin levels go back up and you feel full again. An hour later you are offered Godiva chocolates, a favorite food of yours. You anticipate the pleasure that you will get from eating the chocolates. The pleasure center in your nucleus accumbens releases dopamine which makes you to crave the food even though you are not hungry. This time you give into your cravings and eat the chocolates. Several hours pass and your brain stimulates a hunger sensation around 6 PM when you typically eat dinner.

It is important to understand the ways that your brain anticipates food and causes you to feel hungry. Normally the balance of ghrelin and leptin, in concert with other metabolic hormones, works well enough to control your weight within a narrow range. The constant availability of highly palatable calorie-dense food over the past 100 years is a challenge for our species, which has consumed an unprocessed and bland diet over the past 100,000 years or so. The leptin resistance that develops with obesity makes it even more difficult for your body to feel full after eating and to resist the temptation of eating pleasurable foods.