1. How Scientists Discovered the Hunger Hormone Ghrelin While Searching for a Growth Hormone Trigger
In 1999, a research team led by Masayuki Kojima and Kenji Kangawa was searching for a substance in the body that releases growth hormone. They believed such a substance must exist. They looked for a molecule that would fit into specific "receptors" on the surface of cells, like a key fitting into a lock. [1]
They found a peptide, which is a chain of 28 amino acids. It had a fatty acid attached to the third amino acid. Without this fatty acid "decoration," the molecule did not work. Human ghrelin is said to differ from rat ghrelin by only two amino acids. [1]
The team searched many tissues, not just the hypothalamus, which is the part of the brain involved in appetite. They found the most of this substance in the stomach, so the stomach was identified as the source. [2] The name "ghrelin" comes from the root word for "grow." [1] It was only later that it became known as an appetite hormone.
2. Ghrelin Levels Rise Before Meals and Drop After Eating
Researchers studied how ghrelin levels change during the day. In one study, 10 healthy people had their blood measured for 24 hours. The results showed that ghrelin levels rose by nearly 80% on average before meals. Levels dropped suddenly after eating. [3]
This suggests ghrelin might be a signal to start eating. However, the "80%" figure is an average. Not every person’s levels rise in exactly the same way. Ghrelin travels through the blood and the vagus nerve to the brain. It acts on nerve peptides called NPY and AgRP in the arcuate nucleus of the hypothalamus to increase appetite. Blood levels are highest when you are hungry and drop quickly when you eat. [5]
This raises a simple question: If ghrelin levels are high in the blood, do people really eat more?
3. An Experiment Where Giving People Ghrelin Made Them Eat More
In 2001, Wren and colleagues conducted an experiment with 9 healthy people. They compared days when participants received ghrelin infusions to days when they did not. Neither the participants nor the staff knew which day was which. Then, the participants ate a lunch where they could eat as much as they wanted. [4]
On the ghrelin days, all 9 participants consumed more energy. The average increase was about 28%. They also rated their hunger as higher. However, the speed at which food left the stomach was not affected. This was the first report that ghrelin, circulating in the blood, increases appetite in humans. [4]
If there is an accelerator for eating, is there also a brake?
4. Can Ghrelin Explain Why You Feel Hungry at the Same Time Every Day?
If you eat at the same time every day, you might feel hungry as that time approaches. A study suggests ghrelin might explain this "habitual hunger." In rats, ghrelin levels rose before food arrived when they were fed at fixed times. This happened even if the food did not arrive. Researchers called this a "learned response." [6]
This result is from rats. It is not certain that it applies exactly the same way to humans. But it is an interesting idea that hunger is not just about having little food in the stomach. It may also be a system where the body learns habits and prepares in advance.
5. How Connecting Two Mice Led to the Discovery of the Fullness Signal Leptin
Coleman connected the bodies of two mice so their blood could flow between them. This method is called parabiosis. He reasoned that there must be a factor in the blood that suppresses appetite. [8]
He inferred that "ob" (obese) mice could not make this factor, while "db" (diabetic) mice made it but could not respond to it. This clever reasoning used blood exchange to find the identity of an invisible factor. [8]
Friedman and his team actually found this factor. In December 1994, they cloned the ob gene. In 1995, they showed that injecting the protein into ob mice reduced their food intake. This protein is leptin, made by fat cells. The name comes from the Greek word for "thin." [7] Coleman and Friedman shared the Lasker Award in 2010. [8]
6. Can Leptin Injections Cure Obesity?
In one example of a child born without enough leptin, daily injections helped. A child who was severely obese at age 3 approached the weight range of peers by age 7. [8] The US FDA approved leptin treatment in 2014 for a disease with very little fat. However, this does not mean it works for all obese children. It is just one example. [8]
Most obesity is not caused by a lack of leptin. Instead, people with more fat have more leptin in their blood, but their appetite does not drop. This is called "leptin resistance." Friedman himself expected this, and leptin did not work as a treatment for many obese people. [7] [9]
So what does leptin do? When fasting continues, leptin drops and appetite rises. [10] This suggests leptin acts more as a signal that "fat stores are decreasing" rather than just stopping overeating. Ghrelin from the stomach says "eat soon," and leptin from fat says "stores are low." The brain combines these messages, and it seems that hunger is decided this way. But this is only part of the system; other hormones are also involved.
7. Try This Yourself: Record When You Eat and When You Feel Hungry
For three days, write down the time you eat and the time you feel hungry in a notebook. You might see a connection between your daily habits and hunger. This does not measure ghrelin levels, and it does not prove the rat studies apply to you.
Go to a library and look for books on the human body or hormones. Find diagrams of the stomach and hypothalamus. Tracing where ghrelin and leptin are made and where they go can help you understand this article.
If you have concerns about appetite or weight, do not decide on your own. Ask an adult to help you consult a doctor or specialist.