Leptin Hormone Guide
What is Leptin?
Leptin is a hormone that has many purposes, but primarily it is responsible for the full sensation that we get after the body decides that we've had enough to eat. It is frequently referred to as the “satiety hormone.” Leptin is released by fat cells in an effort to control the way that our body stores fat. In addition to suppressing hunger, leptin also alters the way that our body uses energy.
The fat cells release leptin when they have stored a certain level of fat converted from the calories from the food that we eat. When leptin is released, it enters the blood stream and passes through the body. Leptin travels through the cardiovascular system to the hypothalamus, where it activates special receptors in the arcuate nucleus.
When leptin receptors are activated, it causes the body to increase metabolism, while also reducing signals for hunger. Although this is primarily affected through the brain, there are targets throughout the body which are also responsible for increasing metabolism.
The two hormones, Leptin and Ghrelin, have opposite, component effects upon the body. Whereas leptin controls the feeling of satiation, Ghrelin controls the sensation of hunger. Leptin and Ghrelin receptors are actually located on the same cells, and are two vital hormones responsible for the way that our body both stores and expends energy.
Leptin has a number of different purposes in the body, but the most important of these is considered the regulation of the way that the body stores fat. Our knowledge of how Leptin works is far from complete, but leptin is produced not only by fat cells, but by other organs as well.
Where is Leptin Produced?
The majority of leptin is secreted by white adipose fat tissue by organelles known as adipocytes. Leptin is also secreted from other locations, including the liver, pituitary, bone marrow, epithelial cells, stomach, skeletal muscle, ovaries, placenta, and brown adipose fat tissue.
What Causes Leptin Levels to Fluctuate?
Like other hormones such as Testosterone, Leptin flows through the blood stream both locked into a carrier protein and freely. Because body fat produces leptin, the more body fat that a person carries, the more leptin that they will produce. Perhaps surprisingly, the amount of leptin produced by body fat increases exponentially with the volume of body fat that a person carries.
Leptin concentrations also follow the circadian rhythm under normal circumstances. From around 12am to some point in the early morning, leptin levels remain quite high, which is believed to prevent hunger and promote sleep. Although this is the normal pattern of leptin release and circulation, if a person eats at odd times, such as in the middle of the night, this alters the rhythm of leptin release.
There are many ways that Leptin production is unrelated to body fat as well:
Fasting for one to three days leads to a drop in Leptin production, even if body fat remains the same. Related to this, Leptin levels also drop as a response to starvation, encouraging hunger even when the body still has a large amount of body fat. This is actually one reason why crash diets don't work effectively. Starving yourself will eventually cause you to lose weight, but once you lose the weight, your body will not be able to effectively send signals for satiation, causing you to eat more than your body needs and experience hunger even though you are eating a healthy diet.
Psychological stress increases Leptin Production.
Leptin is affected significantly by sex hormone concentrations in the body. Testosterone is associated with reduced leptin, whereas estrogen is associated with increased leptin. Some hormones released in response to stress, including dexamethasone, also increase leptin secretion.
Physical training will cause leptin levels to drop for the duration of time that a person engages in a healthy exercise routine. This makes sense, because physical exercise stimulates metabolism and increases the need for calories to maintain a certain weight.
The more insulin that your body produces, the more leptin that your body will produce.
For complex reasons, obesity actually leads to an increase in Leptin production.
Overweight individuals with obstructive sleep apnea experience increased leptin levels, but CPAP treatment can bring leptin production back to more normalized levels. Short-term sleep deprivation can lead to a reduction in Leptin production, but long term issues with sleep deprivation, such as sleep apnea, can increase leptin concentrations.
Effects of Leptin
After Leptin is released by body fat and other cells, it suppresses hunger primarily through three mechanisms:
Encourages the production of α-MSH, which suppresses hunger.
Blocks the activity of anandamide, a hormone which encourages hunger via the same mechanism as THC present in marijuana.
Blocks the activity of Neuropeptide Y, a molecule released by the hypothalamus and the stomach which encourages hunger.
In spite of the fact that leptin is the hormone that we most associate with hunger, it is actually only responsible for long-term appetite control. Other hormones are responsible for short term and intermediate hunger:
PYY3-36 is the reason why we don't feel hungry between meals. This hormone encourages us to eat our meals during single sittings.
Cholecystokinin is the hormone which is produced as we eat which inhibits hunger signals. This hormone helps us know when we are full at a particular meal.
Of course, leptin does play a role in the way that these hormones function. Animal research involving leptin clearly shows how the hormone contributes to diet control, as animals which have their ability to produce leptin removed gain weight uncontrollably as a result of a loss of their ability to become full.
Caloric restriction and fasting both have an inhibitive effect upon the production of Leptin. In addition to this, the body is more reactive to the absence of food, rather than its overabundance, so Leptin production will change faster and more dramatically when the body is not getting enough food. This also means that once food access is restored, hunger response won't return to normal as quickly as it was first altered.
Changes in leptin production resulting from abrupt changes in food access appear to be correlated with changes in food intake and diet rather than the energy available that is locked in body fat. This means that leptin suppression due to hunger is not mitigated by existing body fat.
How Does Leptin Control Diet?
Leptin encourages eating and changes in metabolism by triggering receptors in the mediobasal hypothalamus. It used to be believed that blood sugar directly controlled metabolism and eating patterns, but it is clear today that leptin is the mediator of this process.
As we mentioned earlier, Neuropeptide Y activity encourages hunger. There are neurons which produce this hormone in the arcuate nucleus, and as leptin passes through the body, it binds to these neurons, preventing the release of this potent hunger hormone, promoting a disinterest in food. There is also evidence that when Leptin levels are in balance, this makes it easier to eat a healthy diet and not be tempted by the allure of calorie-dense foods.
Prior research has shown that Neuropeptide Y plays an important role in the way that animals eat, including humans. When Neuropeptide Y is artificially introduced to the brain, it automatically triggers the animal to seek out food. The opposite is also true. If the neurons which produce Neuropeptide Y are destroyed, the mice ill become disinterested in eating and become drastically underweight.
Leptin also encourages the release of a peptide known as α-MSH which promotes the feeling of satiety, and genetic abnormalities which limit α-MSH have been shown to increase hunger response and increase the risk of obesity considerably.
Melatonin Affects Leptin Production
In a vacuum, elevated melatonin leads directly to reduced production of leptin. On the other hand, if insulin is in circulation, melatonin leads to an increase in leptin production. This interaction is important because it prevents us from becoming hungry while we are asleep, which can disturb sleeping patterns.
This is why it is generally encouraged to eat a healthy dinner a few hours before bed. This way, your stomach isn't full while you are asleep, but your digestive system is still somewhat active, which means that you have insulin and melatonin in your blood stream, which encourages healthy sleep.
By the end of the night, when insulin levels drop, Leptin levels start to fall as well, as melatonin levels are still elevated. This, in combination with an increase in cortisol and other factors, helps set the stage for you to wake up refreshed and hungry.
Leptin and Diabetes
Preliminary animal research shows that combining leptin with insulin improves metabolism and stabilizes blood sugar more effectively. This combination also helped promote healthier body composition while also balancing cholesterol.
Leptin and the Cardiovascular System
Leptin has an impact on the activity of T-Cells in the immune system. Leptin promotes the health of the heart tissue and healthy leptin levels reduce the inflammatory activity which promotes atherosclerosis. There is also evidence that elevated Leptin levels can help control blood pressure if prescribed medically.
Leptin and the Reproductive System
Leptin does not play any predominant role in human fertility, but it is important and necessary to create the conditions which promote fertility. The regularity of the menstrual cycle depends upon proper metabolism, and is dependent upon the normalized flow of energy through the body, which leptin plays a part in regulating.
If a woman frequently enters a state of starvation, whether purposefully or unintentionally, the menstrual cycle will go into dormancy. Also, if a woman engages in heavy exercise, they also risk entering this state, even if they consume enough calories to meet the demands of their body. On the other hand, menstruation is only affected by low body mass in extreme cases.
In both sexes, Leptin encourages the hypothalamus to produce Gonadotropin-Releasing Hormone, the precursor to Luteinizing Hormone and Follicle-Stimulating Hormone necessary to encourage both sex hormone production as well as sperm production.
Leptin and Pregnancy
During pregnancy, leptin is produced by the placenta, and it continues to be produced in greater concentration throughout pregnancy before returning to baseline after the child is born. This is because leptin has an inhibitory effect upon contractions, allowing the child to develop within the womb. When leptin levels fall, this encourages contractions and helps to stimulate childbirth. Elevated leptin levels also contribute to the condition of morning sickness that commonly takes place during pregnancy.
Leptin and Puberty
There are two hormones which determine when an individual enters puberty: kisspeptin and leptin. In the period just before puberty, leptin levels start to rise, and once they reach a certain point, puberty is triggered. Childhood obesity can lead to early puberty, because adipose fat cells produce leptin, and cause leptin levels to reach the triggering point much faster than in children with normal levels of body fat. There is also evidence that girls that enter puberty early don't grow as tall as their peers, because the increase in estrogen production promotes the closure of the growth plates.
Leptin and Bone Mineral Density
Leptin also appears to help promote healthy bone mineral density. When the brain receives sufficient satiation signals, it then signals the bones to undergo metabolic changes which promote cortical bone growth and inhibit cancellous bone. Cancellous bone is the softer tissue in the core of the bone, and cortical bone is the hard casing which covers the cancellous bone. Thus, leptin plays a role in bone maturation during puberty because the bones become thicker and harder, allowing them to carry more weight.
After puberty, leptin still plays a role in bone metabolism, because once it activates at its receptor sites on the hypothalamus, is alters the production of a number of other hormones and peptides associated with the regulation of bone mineral density. There is also some evidence that Leptin directly contributes to increased bone mineral density by playing an intermediary role between metabolism and the release and activation of Insulin-Like Growth Factor-One. As a result of this connection, there may be treatments in the future which utilize leptin in order to enhance the natural healing processes of bone tissue after breaks and fractures.
Leptin and the Brain
Although the primary trigger point for leptin is the hypothalamus, there are also receptors for the hormone at other locations within the brain. One of the largest receptor sites outside of the hypothalamus is the hippocampus.
Research has clearly shown that Leptin Deficiency has a negative impact on the normal function of neurons as well as brain proteins. In animal studies, normal neurological function in this instance can be restored by providing injections of leptin.
In humans, Leptin Deficiency is associated with neurological and cognitive changes that are associated with HIV, depression, and anorexia. There is even evidence in rats that leptin deficiency may play a role in Alzheimer's, and that providing leptin therapy may be able to increase cognitive ability and reduce the negative effects of the disease by limiting the concentrations of hyperphosphorylated tau and b-amyloid, which are two of the main factors which make Alzheimer's such a devastating neurological disorder.
Leptin and the Immune System
Leptin is intricately related to the immune system response of inflammation, and leptin has a regulatory effect upon a number of factors which affect immune health, including body fat, caloric restriction, stress, sleep, and Testosterone levels. It is hypothesized that the primary mechanism which links Leptin to immune health is that Leptin helps control the activity of cytokines released by adipose tissue.
Leptin is actually structurally similar to cytokines both in function and its molecular composition. There is evidence that Leptin plays an active role in the way that the body handles and manages stress, but the direct mechanisms are not completely understood. There is also a positive correlation between white blood cell count and leptin levels.
Diseases Associated with High Leptin Levels
There are a number of medical conditions which are associated with abnormally high leptin levels, especially those associated with inflammation. Among these are cardiovascular disease, chronic fatigue, and hypertension.
Elevated levels of leptin are correlated with overeating, the mass of adipose fat cells, and overall body composition, but leptin is not connected in any way to physical activity. Exercise does not stimulate or suppress the production of leptin directly. For this reason, it is hypothesized that leptin is designed to activate only with regard to inflammation related to adipose fat. Leptin promotes the formation of new blood vessels, promotes inflammation, and encourages cellular metabolism.
Based on these factors, it is believed that the elevation of leptin levels due to overeating is a mechanism designed to limit the stress on fat cells caused by abrupt changes related to increased caloric intake. When the fat cells no longer have enough room to absorb all the calories being delivered, this causes the body to begin to store fat in the muscles, arteries, and organs, which is dangerous.
So in this sense, leptin triggers satiation in order to prevent the body from eating so much that the fat cells can no longer make room for it all, but obesity causes the body to produce too much of the hormone, which can have negative effects. Like other inflammatory/stress hormones, the body needs leptin, but there are serious issues which can result when the hormone is allowed to remain at abnormally high levels for too long.
The Facts on Leptin: FAQ - The Truth about the Hormone Leptin and Obesity
Serum Leptin Levels in Males with Delayed Puberty during Short-Term Pulsatile GnRH Administration.