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Leptin Facts and Effects on Appetite and Lipodystrophy

Linda Crampton is a writer and teacher with a first-class honors degree in biology. She often writes about the scientific basis of disease.

The main way in which leptin reduces appetite is believed to be via its effect on the hypothalamus in the brain (the circled blue area in the illustration).

The main way in which leptin reduces appetite is believed to be via its effect on the hypothalamus in the brain (the circled blue area in the illustration).

An Interesting and Significant Hormone

Leptin is a protein produced by our white fat cells and other parts of our body. It acts as a hormone and decreases appetite once we have eaten enough food for our needs. It also has many other potentially important effects. It's used as a medicine for people who produce no or little leptin. The protein is an interesting chemical whose behavior isn't completely understood

If patients are deficient in leptin and overweight as a result, administration of the chemical can cause weight loss. The substance is also used as a treatment for patients with a condition called lipodystrophy. In this disorder, a person's body has an abnormally low amount of body fat and therefore doesn't make enough leptin. Scientists need to learn more about how leptin behaves in the body in order for it to be more widely used as a medicine.

The word "leptin" comes from leptos, the Greek word for thin. The hormone was discovered in 1994 by two scientists: Jeffrey Friedman from Rockefeller University in New York and Douglas Coleman from the Jackson Laboratory in California. They identified the substance in mice and later found it in humans. Friedman continues to study leptin. Unfortunately, Coleman died in 2014.

Leptin Structure and the Ob Gene

Proteins consist of chains of molecules known as amino acids. There are thousands of amino acid molecules in some proteins. Only twenty specific types are commonly present in human proteins. They are arranged in different orders and repeated a different number of times to create the proteins. Some proteins contain multiple chains of amino acids that are connected to one another by chemical bonds. A leptin molecule contains 167 amino acids in total and consists of a single chain.

Genes contain instructions for making proteins. The instructions are created via a specific sequence of chemicals in the nitrogenous base group. The sequence of nitrogenous bases in a gene controls the order of amino acids in a protein. A gene is said to "code for" a specific protein. The one that codes for leptin is known as the ob or obese gene.

A chain of amino acids in a protein may have complex folds. The molecule as a whole has a specific shape.

A chain of amino acids in a protein may have complex folds. The molecule as a whole has a specific shape.

Hormone Production by Adipocytes

Leptin is often referred to as a hormone. A hormone is made in one part of the body and then transported to another part in the bloodstream, where it exerts its effects. It's made by fat cells, or adipocytes.

Leptin is produced primarily in the white fat adipocytes. These cells store a single large fat droplet, which can be used to produce energy. The cells are located mainly in fat deposits under the skin. Fat in this location is known as subcutaneous fat. Brown fat adipocytes make a smaller quantity of leptin. They contain multiple small fat droplets and more mitochondria (energy-producing organelles) than white adipocytes. Mitochondria contain iron, which gives brown adipocytes their color. Adults have far more white fat than brown fat.

If the body doesn't need energy, fat droplets continue to be stored in the white adipocytes. This process can gradually create deposits of fat that can be unhealthy if they're extensive or located deeper in the body, such as around organs.

As research continues, scientists are discovering that leptin is made in other parts of the body besides fat and that it produces multiple effects. It seems to act as a signaling molecule that influences multiple systems and processes. It's sometimes referred to as a cytokine (a cell signaling molecule) or an adipokine (a cytokine made by adipose tissue) instead of a hormone. Adipose tissue is a collection of cells in which fat is stored.

Union With Cell Receptors

A human cell is not an isolated entity. The surface membrane covering a cell contains receptors of various types. Each type of receptor joins to a specific substance in the surrounding environment. The union triggers a particular process in the cell.

A leptin molecule joins to leptin receptors on the surface of cells. Its effects appear to vary depending on the type of cell that is stimulated, though this impression may be at least partially due to our lack of knowledge. It may affect a particular process directly or indirectly. At the moment, the range of cells that the chemical affects is impressive but somewhat puzzling.

Reduction of Appetite

Someone who starts to explore human physiology and biochemistry in depth will quickly discover that it’s a complex topic containing many puzzles. Despite the complexity, understanding the processes that occur in the body is important because it could lead to new medical treatments. This is very likely the case with respect to leptin.

Leptin seems to reduce appetite mainly by its effects on the hypothalamus in the brain. It's released by the adipocytes, enters a blood vessel, and is transported to the brain by the bloodstream. Here it crosses the blood-brain barrier (BBB), enters the hypothalamus, and binds to receptors on specific cells.

The blood-brain barrier consists of tightly packed endothelial cells in the lining of the blood vessels of the brain. The barrier prevents the vessels from allowing harmful substances to enter the brain tissue. Some substances can pass through the barrier, however, including leptin. It has been suggested that one reason why leptin can become ineffective in obese people is because the substance can no longer pass through the BBB. So far, however, no evidence supporting this idea seems to have been discovered.

Inhibition of AgRP and NPY Neurons

At least one method by which leptin acts once it enters the hypothalamus is by the inhibition of AgRP neurons (or nerve cells). The abbreviation "AgRP" stands for agouti-related peptide. The peptide is produced by the neurons. The agouti is a South American rodent. It's natural that someone who's heard of the animal might wonder if the neuron's name is related to them. The only reference about the name that I've found says that the theories about the evolution of the peptide's nomenclature are controversial.

The AgRP neurons are located in the hypothalamus. The peptide that they release increases appetite. By inhibiting the action of the neurons, leptin decreases the appetite. Leptin also inhibits the hypothalamic neurons that secrete neuropeptide-Y, or NPY. Like AgRP, this peptide increases appetite.

In obesity, the AgRP and neuropeptide-Y neurons often fail to respond to leptin's inhibitory signal for reasons that are unclear. If the person loses weight, the sensitivity of the neurons to leptin is sometimes re-established.

It's probably too simplistic to say that everyone with a big appetite has a leptin problem, but the situation may be present in some people.

It's probably too simplistic to say that everyone with a big appetite has a leptin problem, but the situation may be present in some people.

Leptin Deficiency and Resistance

When leptin was first discovered, it was thought that it would be a good treatment for leptin-deficient individuals who had gained weight. This has proved to be the case. Unfortunately, the situation is more complicated than it first seemed.

Research has shown that while leptin deficiency occurs in some people, leptin resistance is a far more common condition. The term "leptin resistance" means that leptin is present at a normal level, but the body isn't responding to its presence. This situation needs to be understood in more detail in order to help people.

What Are Leptin Supplements?

Leptin supplements and products with a similar name are generally sold over-the-counter (that is, without a prescription). Though the term "leptin supplement" suggests that a product contains leptin, it doesn't. Instead, it contains substances that the manufacturer says will help the hormone to work or substances that make a person feel full.

Some manufacturers claim that a particular supplement's ingredients help leptin to communicate with the brain in overweight people. I think if this were possible the ingredients would be used in a prescribed medication. Anyone who wants to use one of the supplements should show their doctor the ingredients and ask if they are of any use.

Even if the supplements contained leptin, they wouldn’t be useful. Leptin is a protein. Like other proteins in our food, if it’s taken by mouth, it’s broken down into amino acids by enzymes in the digestive tract. The amino acids are then absorbed into the bloodstream. (The same situation is true for any other proteins in a supplement.) Leptin used medicinally is injected directly into the bloodstream, where it can stay intact.

White adipocytes and subcutaneous fat

White adipocytes and subcutaneous fat

Lipodystrophy

Lipodystrophy is a condition in which patients have an abnormal distribution of body fat. In some individuals, subcutaneous fat may be almost completely lost from many parts of the body. The fat under our skin cushions our body from blows, so its loss can make life painful. Fat loss from the face can make a person look much older than they are.

Unfortunately, a person with lipodystrophy experiences additional problems. Though fat just under the skin is lost, it may collect internally in places where it's harmful, such as in the liver and other organs. In addition to the fat problem, the person is extremely hungry all the time. The food that they eat doesn't relieve their hunger.

Lipodystrophy is sometimes localized and may not be a big problem, but generalized lipodystrophy can be a major disorder. The absence of much of the body fat except for the internal type is associated with other health problems. They include insulin resistance, diabetes, a high level of triglycerides in the blood, non-alcoholic fatty liver disease, and kidney problems. Fat in the liver is sometimes known as steatosis.

Lipodystrophy is characterized by a very low level of leptin because many of the adipocytes that make it are missing. Given the fact that leptin has many different functions beyond regulating appetite, its absence may be serious. Fortunately, leptin is an FDA-approved treatment for lipodystrophy. (The FDA, or the Food and Drug Administration, regulates medicinal drugs in the United States.) In the US, the medication may be administered in a synthetic version known as metreleptin or by the brand name Myalept®.

A role of leptin in hepatic lipid handling is highlighted by the observation that recombinant leptin reverses steatosis of hypoleptinemic patients with lipodystrophy by an unknown mechanism.

— Hackl et al, via the National Library of Medicine, with respect to fat storage in the liver

Leptin Administration in Lipodystrophy

Though there are probably additional factors involved in the disease, lipodystrophy demonstrates the importance of leptin in the body. The fact that a lipodystrophty patient develops problems in multiple organs and functions with insufficient leptin suggests that the hormone plays a role in many processes.

As the interview in the video above and in the NOVA article referenced below show, the leptin treatment doesn't cure the disease or stimulate the production of the missing body fat. The patient still has a very low level of fat under their skin and the problems that that state causes. However, the ravenous hunger that was interfering with their life has disappeared. In addition, their liver is now said to be protected. The recombinant leptin referred to in the quote above is made in the lab and has been shown to be helpful for the removal of liver fat in people with lipodystrophy.

The website of the company that produces Myalept® acknowledges that the medication "treats certain problems from not having enough leptin" instead of curing the disorder. It says that the medication lowers blood sugar and blood triglyceride levels, which are important effects. Triglycerides are fat molecules.

Scientists have also found evidence that leptin can lower a high blood sugar (or blood glucose) level and (at least in rats) a high triglyceride level. Hopefully, researchers will soon find a way to trigger body fat replacement in lipodystrophy patients and return them to health.

Leptin exerts a plethora of metabolic effects on various tissues including suppressing production of glucagon and corticosterone, increasing glucose uptake, and inhibiting hepatic glucose output.

— D'souza et al, The glucoregulatory action of leptin, via ScienceDirect

A Worthy Chemical to Investigate

Leptin appears to be a very worthy chemical to investigate. Though I've focused on reduction of appetite and helping lipodystrophy patients in this article, other body processes are affected by leptin. The hormone's role in controlling blood glucose and triglyceride levels could be very important. Researchers are exploring how the substance might help diabetics.

Another point of interest in research is that additional substances besides leptin affect appetite. Untangling the branched and intersecting pathways in human biochemistry can be difficult, but the rewards can be tremendous. Once we improve our understanding of how it behaves, leptin or other chemicals in the pathways that include it might be very useful as medicines for specific health problems.

References

  • Food intake regulation by leptin from ScienceDirect (Abstract)
  • Lepton modulates the excitability of AgRP/NPY neurons from The Journal of Neuroscience
  • Facts about acquired lipodystrophy from WebMD
  • An interview with a lipodystrophy patient treated with leptin from the NOVA website (A transcript of the interview is provided.)
  • The glucoregulatory actions of leptin from ScienceDirect (Abstract)
  • Brain leptin reduces liver lipids in rats from the National Library of Medicine

This content is accurate and true to the best of the author’s knowledge and does not substitute for diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed health professional. Drugs, supplements, and natural remedies may have dangerous side effects. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

© 2020 Linda Crampton

Comments

Linda Crampton (author) from British Columbia, Canada on December 06, 2020:

Hi, Miebakagh. I’m glad your ISP problems are solved.

I think you are misunderstanding the action of leptin. Leptin is a hormone that triggers processes in our body that decrease our appetite when we've eaten enough food. Therefore, if we have no leptin, the inhibitory effect of leptin on our appetite will not be present. As a result, we will eat too much and gain weight (assuming other health problems that prevent the weight gain aren't present).

Miebakagh Fiberesima from Port Harcourt, Rivers State, NIGERIA. on December 06, 2020:

Linda, you're welcome. First, forgive me for responding late because I had an issue with my ISP and my phone, the only device I used to communicate. All is now working fine. Without the fat protein leptin, one will not eat and get or store energy. But certain person will not produce enough to be hungry and eat. Is not this why they stay thin no matter how healthy these eat the best nutrient? This is the point I try to stress. I agree with all you say on research. But a physician with a good background of chemistry or a nutrition chemist, I bet will be the first with an answer. Much thanks. Enjoy the week.

Linda Crampton (author) from British Columbia, Canada on December 05, 2020:

Thank you for reading the article and for commenting, MG.

MG Singh emge from Singapore on December 05, 2020:

It is a subject on which I know nothing but it was very nice reading it.

Linda Crampton (author) from British Columbia, Canada on December 05, 2020:

Thank you, Devika. I appreciate your visit.

Devika Primić from Dubrovnik, Croatia on December 05, 2020:

AliciaC Most interesting about Leptin facts I found your hub informative and improved my knowledge on this topic.

Linda Crampton (author) from British Columbia, Canada on December 05, 2020:

Thanks, Fran.

fran rooks from Toledo, Ohio on December 05, 2020:

ditto

Linda Crampton (author) from British Columbia, Canada on December 05, 2020:

Thanks, Fran. I hope you have a good weekend.

fran rooks from Toledo, Ohio on December 05, 2020:

Another informative biology article. I always learn so much from your articles.

Linda Crampton (author) from British Columbia, Canada on December 03, 2020:

I appreciate your kind comment, Liza. Thank you for reading the article.

Liza from USA on December 03, 2020:

Our body is so fascinating! In the beginning, the topic is quite intricate for me. However, as I was reading thoroughly, I have a better understanding of Leptin. I get hooked reading such a well-written article, and you've explained it very well. Thanks for sharing, Linda.

Linda Crampton (author) from British Columbia, Canada on December 03, 2020:

Thank you very much, Fran.

fran rooks from Toledo, Ohio on December 03, 2020:

Wow, Alicia, another great and informative article. Thanks for the info.

Linda Crampton (author) from British Columbia, Canada on December 02, 2020:

I appreciate your kind comment very much, Manatita. It is a shame that the researcher didn't live for longer. The more minds that study leptin's behavior, the better!

manatita44 from london on December 02, 2020:

Eloquently and very professionally expressed. Some truly significant uses and I would say that perhaps, if the scientist had not passed on, we'd probably be further along the road of interesting discoveries.

Leptin most certainly has more uses as yet unknown to us. A very informative and educational piece!

Linda Crampton (author) from British Columbia, Canada on December 02, 2020:

Hi, Denise. I think leptin does seem like a hormone that should be watched. It has a lot of potential.

Thanks for the comment. Blessings to you.

Denise McGill from Fresno CA on December 02, 2020:

If it can reduce blood sugar it may be something that could help the diabetic also. This does seem to be something to watch. Amazing how they learn new things every year about or complex bodies. I've always been on the chubby side and as a teenager, I was given thyroid tablets which didn't help that much. Since then I just have to watch my portions.

Blessings,

Denise

Linda Crampton (author) from British Columbia, Canada on December 02, 2020:

Thank you very much, Brenda. Leptin could be very useful in medicine. I hope it lives up to its promise.

I hope you have a great day, too.

BRENDA ARLEDGE from Washington Court House on December 02, 2020:

You did a great job writing this one.

Leptin sounds like something that could be a valuable resource if it indeed proves to help those with diabetes and control triglyceride level.

Have a great day.

Linda Crampton (author) from British Columbia, Canada on December 02, 2020:

Hi, Peggy. Thank you for the visit. I think the processes that take place in the human body are fascinating.

Peggy Woods from Houston, Texas on December 02, 2020:

Once again, you have focused on part of what makes up our bodies and how leptin research might help in the treatment of different conditions like diabetes, obesity, etc.

Linda Crampton (author) from British Columbia, Canada on December 02, 2020:

Thanks, Ankita. Leptin and its behavior are certainly complex. The study of the chemical by experts could be very helpful for us, though. I hope that's the case.

Linda Crampton (author) from British Columbia, Canada on December 02, 2020:

I appreciate your visit and comment, Eman.

Linda Crampton (author) from British Columbia, Canada on December 02, 2020:

Thank you once again, Bill. I always appreciate your comments and support.

Linda Crampton (author) from British Columbia, Canada on December 02, 2020:

I appreciate your comment, Pamela. Thank you for the visit and for reading the article,

Linda Crampton (author) from British Columbia, Canada on December 02, 2020:

Hi, Miebakagh. Thanks for the comment. Like other proteins, leptin is made in our body via the process known as protein synthesis. It’s produced in other mammals besides humans. Eating animals doesn’t help us with respect to obtaining leptin, however. Like other proteins, leptin is broken down into amino acids or into very short chains of amino acids known as peptides in our digestive tract. It isn’t absorbed in the intact form.

Though humans can’t make biotin or vitamin B12, the substances are made in nature. They are both produced by certain bacteria.

I think that research from any scientists can be helpful, whether the scientist is a biologist, a chemist, or a doctor who is a medical researcher. I hope more facts about leptin are discovered soon.

Ankita B on December 02, 2020:

A very interesting and well-explained article about Leptin. Always get to learn so much from your articles. Leptin is truly a very complex chemical.

Eman Abdallah Kamel from Egypt on December 02, 2020:

Thank you, Linda, for this useful and educational article.

Bill Holland from Olympia, WA on December 02, 2020:

Fascinating as always, my friend. I always learn something of interest from your articles.

Pamela Oglesby from Sunny Florida on December 02, 2020:

This is obviously a very well-researched and interesting article. I was not familiar with lipodystrophy and I didn't know much about leptin either. Thanks for such great details. I am going to read the article again for better understanding.

Miebakagh Fiberesima from Port Harcourt, Rivers State, NIGERIA. on December 02, 2020:

Lindah, this is an interesting read and educative. My pleasure. Like insulin, it seems the body cannot make enough of the leptin to counter the trigger of the hypothalamus or otherwise. It seems also that like biotin vitamin H: or vitamin B 12, leptin is not made in nature. This is a complication for the physicians. These proffesionals hardly found an answer to the issue. It is mostly the work of human biologists or chemist. Notwithstanding that, some day the answer will be reveal even by medical researchers. Thanks for the good read.

Linda Crampton (author) from British Columbia, Canada on December 02, 2020:

Thank you, Chitrangada. I appreciate your visit and comment. You've raised a good point about non-prescription medications.

Chitrangada Sharan from New Delhi, India on December 02, 2020:

A very well explained article, with relevant information about the Leptin. It's good to understand It's role in our physical health, but we should avoid self medication. The problem with over the counter medicines is that, sometimes people start taking them, without examining their health condition with other necessary associated illnesses.

Thank you for sharing this excellent article and the education.

Linda Crampton (author) from British Columbia, Canada on December 01, 2020:

Thank you very much for the visit and comment, Liz. I think that hormones are interesting as well as useful.

Linda Crampton (author) from British Columbia, Canada on December 01, 2020:

Hi, Umesh. I appreciate your comment. Leptin is an interesting chemical. Its behavior and interactions are complex, but I think it's important for scientists to study them because the hormone affects our health. Best wishes to you.

Liz Westwood from UK on December 01, 2020:

This is a very interesting, well-researched and well-presented article. I had heard of weight issues attributed to hormones in the past, but knew little about the science behind this. Your helpful article explains a lot.

Umesh Chandra Bhatt from Kharghar, Navi Mumbai, India on December 01, 2020:

This is a complex subject, in fact most of the topics in biology and medical science are like that only.

I had studied biology only up to my class 10 and later had some interest in medical articles as a hobby and not as an academic interest.

With that background, what I could gather from this is that this protein has a big role in weight reduction and can be a boon for the obese persons if administered in proper ways. Another is that there is a lot of work still to be done to understand it's interaction with other chemicals in other places in the body including hypothalamus of course.

Thanks for such an excellent article illustrated in a simple way though the topic is a difficult one.

It is difficult to catch your articles for comment as they move very fast to niche sites specially after formation of discover.hubpages.

Anyway keep up your nice work in hubpages and God bless you.

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