Hormones That Control Appetite: Leptin and Ghrelin
Leptin and ghrelin are protein hormones that control our appetite. They are made in our bodies and were each discovered quite recently—leptin in 1994 and ghrelin in 1999. Leptin reduces our appetite and is produced mainly by the adipocytes (fat cells) in our white fat, which is also known as white adipose tissue. Ghrelin stimulates our appetite and is made chiefly by the stomach.
Researchers are still trying to discover exactly how the hormones work. Like other hormones, they have complex actions and multiple functions. The study of leptin and ghrelin is exciting, however, because in the future it may be possible to use these proteins—or our knowledge about how they work—to help control people's weight. We may be able to help leptin work more effectively or suppress the action of ghrelin, for example. The most important goal of the research is to reduce the increasing prevalence of obesity in many societies.
Discovery of Leptin
Leptin was discovered by Jeffrey Friedman from the Rockefeller University and Douglas Coleman from the Jackson Laboratory. They learned about the hormone and its effects by studying obese mice, but researchers soon found that the discoveries applied to humans as well.
The work of Friedman and Coleman was a major breakthrough in removing the impression that all obese people are overweight due to a lack of willpower in their eating habits. In fact, in the video below, Jeffrey Friedman says that he thinks that obesity is caused chiefly by biological problems.
Although leptin plays an important role in controlling body mass, it's not the only substance that has this function. Biological control of weight is a complex process that seems to involve many chemicals.
A Researcher Discusses Leptin and Obesity
Production of the Hormone
A leptin molecule is made of 167 amino acids. Its name comes from the Greek word "leptos", which means "thin". The hormone is produced in the adipocytes of our white fat, or white adipose tissue (WAT). Each WAT adipocyte is a cell containing a large fat or triglyceride droplet. Leptin is also made in much smaller quantities in other areas of the body, including in our deposits of brown fat or brown adipose tissue (BAT).
The greater the amount of body fat, the higher the amount of leptin in the blood. In addition, women seem to make more leptin than men. The production of the hormone is controlled by the obese gene, which is also called the ob gene. Mutations, or changes, in this gene can create problems.
A Leptin Molecule
Hormone Action and Hunger
Excess food in our diet is converted into fat. As the amount of fat deposited in our adipose tissue increases, leptin is released from the adipocytes into the bloodstream. The larger the adipocytes become, the greater the amount of leptin released. The hormone travels to the brain via the bloodstream and attaches to the receptors on cells in the hypothalamus, the section of the brain that controls appetite. The binding process stimulates the hypothalamus to reduce our sensation of hunger. The fat deposition and the subsequent leptin release "tell" the hypothalamus that we've eaten enough food and no longer need to make eating a priority.
When the amount of fat stored in the body decreases, the amount of leptin released into the blood also decreases. When fewer leptin receptors are stimulated, the hypothalamus triggers our hunger and causes us to eat more food, which replaces our fat stores. Under normal conditions leptin activity helps to keep our weight constant as the amount of body fat is adjusted.
Location of the Hypothalamus in the Brain
Further Actions of the Hypothalamus
When leptin binds to its receptors it may influence the action of other chemicals instead of or as well as stimulating hypothalamus action directly. One chemical that has frequently been linked with leptin activity is a small protein called neuropeptide Y, or NPY. This protein is secreted by the hypothalamus and by cells in the intestine. It stimulates feeding behavior in lab animals. Leptin seems to inhibit the activity of NPY.
Another protein that is believed to play a role in leptin action is Janus kinase 2, also known as JAK2. This chemical acts as a signaling molecule. Understanding the role of other chemicals involved in leptin activity is important because it may enable researchers to create new treatments for obesity.
The hypothalamus controls energy expenditure in the body in addition to controlling our appetite. Some research suggests that leptin boosts energy expenditure in humans, but not all research supports this idea.
Leptin supplements are available. Scientists say that ingesting these supplements isn't an effective way to lose weight, for several reasons. Since leptin is a protein, enzymes in the digestive tract break it down before it's absorbed into the bloodstream. In addition, "leptin" supplements generally don't contain any leptin, but instead contain substances that the manufacturers claim are leptin helpers, such as certain fatty acids.
Another problem is that researchers have discovered that most people don't lack leptin. In fact, obese people generally have a higher than normal level of the hormone. These people may develop leptin resistance, however, a condition in which their body no longer responds to the presence of the leptin in their bloodstream. It should be noted that some researchers feel that the term "leptin resistance" is not always used appropriately when describing a problem involving the hormone.
Another cause of obesity is the complete lack of leptin. In this case, leptin provided by injections instead of in a supplement form does help people lose weight. The weight loss is often dramatic and very satisfying for the formerly obese person.
Researchers still have many questions about why some some people appear to be leptin resistant while others are sensitive to the hormone. They do have some theories about the causes of the hormone resistance. The disorder may develop due to a malfunctioning of the leptin receptors in the hypothalamus, for example. If the receptors don't operate properly or have the wrong structure, leptin will be unable to bind to them and the hypothalamus won't reduce the desire to eat. Another possibility is that the leptin molecules may have an altered structure and be unable to attach to the receptors. Leptin resistance may also be due to the inability of the hormone to enter the brain.
Scientists need to determine the specific causes of leptin problems before they can devise treatments. It's a difficult task, but researchers are continuing to investigate the hormone and its actions. Until more effective treatments are created (and after a treatment is found), people diagnosed with resistance to leptin should exercise regularly, provided their doctor says that this is safe. Calorie restriction may not be possible, but it's still important to reduce sugar in the diet and to eat healthy fats instead of unhealthy fats. Some prescribed medications for other health problems may be helpful for patients. Obese people should visit their doctor regularly so that their health can be monitored and they can get advice that may improve their condition.
Location of the Pituitary Gland
Ghrelin and Its Discovery
Ghrelin was discovered by Masayasu Kojima and his colleagues. A ghrelin molecule is made of 28 amino acids. The gene that contains instructions for making ghrelin actually codes for a longer protein called preproghrelin. This protein is made of 117 amino acids and breaks down to make ghrelin and another protein. In 2005, researchers at Stanford University named this other protein obestatin and claimed—controversially—that it reduces appetite.
The stomach makes the largest quantity of ghrelin. Other parts of the body, including the intestine, the hypothalamus, and the pituitary gland in the brain, make smaller quantities of the hormone. Like all hormones, ghrelin is released into the bloodstream and travels to its target organ.
Obesity in Children and the Function of Ghrelin
Ghrelin is sometimes called the hunger hormone because it makes us hungry. It's sometimes known as lenomorelin.
Function of Ghrelin
The hypothalamus contains ghrelin receptors as well as leptin receptors. When the ghrelin molecules join to their receptors, the hypothalamus causes the sensation of hunger. Ghrelin also joins to receptors on the pituitary gland and triggers the production of growth hormone.
Ghrelin is secreted when the stomach is empty. When the stomach is stretched after eating, the production of the hormone decreases. The ghrelin level in our bloodstream is therefore highest just before we eat and falls shortly after we've eaten. A few hours after eating the hormone level rises again, stimulating us to eat our next meal.
Ghrelin produces a rapid effect once it's released. People injected with the hormone quickly become very hungry. Researchers have found that ghrelin also stimulates us to prefer high calorie foods compared to low calorie ones.
Sleep and Hormone Levels
Some researchers have shown that ghrelin and leptin levels are altered in people who lack sleep. The scientists have found that the ghrelin level is higher and the leptin level is lower in people who sleep for six hours or less a night compared to the levels in people who receive more sleep. They have also found that some of the people who sleep for an insufficient time gain weight.
The studies described above don't prove that lack of sleep is the reason for hormone level changes and weight gain, but the potential link is very interesting. Researchers already know that getting sufficient sleep is very important for our health. If it also helps to prevent weight gain, that's another bonus of getting an adequate amount of sleep each night.
Hope for the Future
Leptin research has led to a very successful treatment for obese people who make little or no leptin. Treating leptin resistance is a much harder job. There was great excitement when leptin was first discovered, but now people realize that more research is needed to make further use of the discovery.
Researchers are investigating the potentially beneficial effect of leptin in type 2 diabetes. This benefit seems to be independent of the hormone's ability to help some obese people lose weight. Obesity is a known risk factor for type 2 diabetes.
Like leptin, ghrelin is a very interesting hormone. Controlling its level in the body may someday be a helpful treatment for people who are having trouble losing excess weight.
The human endocrine or hormonal system is complex, but its study is very worthwhile. Hopefully new therapies and medications will soon be developed for treating problems such as leptin resistance and obesity.
- Leptin information from WebMD
- Myers, M. G., Heymsfield, S. B., Haft, C., Kahn, B. B., Laughlin, M., Leibel, R. L., … the attendees* of the NIH conference “Toward a Clinical Definition of Leptin Resistance.” (2012). Defining Clinical Leptin Resistance - Challenges and Opportunities. Cell Metabolism, 15(2), 150–156. http://doi.org/10.1016/j.cmet.2012.01.002
- Ghrelin and the desire for high-calorie foods from Science Daily
- Sleep deprivation and hormone levels from Scientific American
© 2012 Linda Crampton