The hormone leptin was discovered more than 20 years ago. Since that time, a tremendous amount of information has been discovered about leptin and its many effects. Leptin is still at the forefront of metabolic health, but it is far more than that. As scientists unearth leptin’s role in other areas, we find that it is intimately involved with inflammation, especially autoimmune inflammation.

Too much leptin, leptin resistance, and even too little leptin greatly affects the immune system and more. In a modern world that often offers high calorie, nutrient poor diets with grazing and disrupted schedules that impact leptin, there is no doubt that this has contributed to the epidemic levels of obesity. Increasing evidence shows that high leptin levels impact autoimmune disorders and even the obesity-cancer connection. Mastering leptin is still at the forefront of daily health.

The Role of Leptin

Leptin is a hormone, or adipokine, produced by fat cells. Leptin is also found in smaller amounts in the brain (hypothalamus, pituitary), stomach and intestines, skeletal muscle, breast tissue, cartilage and bone cells, placenta, and immune cells. Leptin was initially considered an anti-obesity hormone, but it influences the formation of all types of blood cells (hematopoiesis), heat and energy production (thermogenesis), reproduction, new blood vessel formation (angiogenesis), and most importantly, immune homeostasis. 

In addition to being a hormone, leptin is also a cytokine, an immune compound capable of immune responses and inflammation. It is directly involved with the interplay between metabolism and inflammatory responses. This is seen as an almost circuitous loop as fat cells produce leptin which assists in the secretion of proinflammatory cytokines like TNF-a, IL-1, and IL-6 and others. In turn, these and other cytokines promote release of leptin from fat cells, which can create a cyclical response. With higher body mass index (BMI) as in obesity, increased leptin leads to increased inflammation.

In addition to the proinflammatory cytokines stimulating leptin, other factors influence leptin levels. Hormones like insulin and cortisol impact leptin levels. High calorie intake, low nutrient intake, and mistiming of meals affect leptin. Acute infections, LPS toxins which are toxic by-products from bacteria, and severe overwhelming infections also increase leptin levels. Women also have higher leptin levels than men.

Leptin Related Disorders

High leptin contributes to increased likelihood of developing cardiovascular disease, diabetes, cancer, degenerative joint disease, surgical complications, and autoimmune disorders. It is involved with allergic disorders and oral health. 

Elevated leptin levels are thought to contribute to systemic autoimmune disease like type 1 diabetes and inflammatory bowel disease. Leptin is elevated in inflammatory nephritis/kidney disease, endometriosis, nonalcoholic hepatitis, chronic pulmonary/lung inflammation, Behcet’s disease, and even Grave’s disease (thyroid). More recent research shows that elevated leptin may contribute to autoimmune disorders that affect connective tissues such as inflammatory arthritis, i.e. rheumatoid, osteoarthritis and vasculitis.

Additional research shows that elevated leptin stimulates the disease process with the connective tissue disorder, systemic lupus erythematosus (SLE) or lupus. Obese patients with elevated leptin are more likely to develop multiple sclerosis. Liver cirrhosis may also occur with increased leptin levels because of its proinflammatory scarring that induces fibrotic tangles in the liver.

Elevated leptin levels are seen in the brain with Alzheimer’s disease. In this case, it is thought that leptin receptor sites are damaged from the brain tangles from the disease process. This is thought to interfere with the normal leptin signaling pathway and create a different type of leptin resistance.

Leptin and Immune System

Leptin is directly involved with immune balance and homeostasis as it talks directly to the thymus gland and is essential for the thymus gland to mature. Here are some basic things that leptin is known to influence in the immune system. Leptin promotes T cell activation and can shift the body towards a Th1 dominant response while suppressing Th2 immune balance. It also affects the production of natural killer cells. Several of the disorders listed above are considered Th1 dominant disorders.

Chronically elevated leptin changes natural killer cell function in the body. Natural killer cells are innate immune cells that are essential to immune defense. Their primary purpose is to kill tumor cells and virus-infected cells. When natural killer (NK) cell function is impaired from elevated leptin, the total number of NK cells decrease and tumor cell killing capacity becomes compromised. Researchers suspect that this may be one reason for increased cancer susceptibility in obese individuals.

There is a flip-side to leptin, as low leptin levels contribute to other dynamics with the immune system. Individuals who have low leptin and are malnourished have an increased risk of infection and other issues of impaired immune function. The focus of this article though is on elevated leptin and the immune system.

Leptin and Inflammation Modulation

Researchers are still trying to figure out how to manage leptin with drugs in order to block, modulate, or make more leptin hormone. There is, however, a natural way to help modulate leptin. Several resources exist. Here are some recent studies describing natural support for leptin modulation.

Leptin and autoimmunity research is a fascinating topic and one that will be explored for years to come. This article only scratches the surface of the topic, but it gives important clues. Leptin’s effect on the immune system is profound. When it fails to be in balance, then the propensity is to develop significant dysregulation, chronic low-grade inflammation, degenerative disease and autoimmune disorders. Autoimmune disorders and obesity statistics has increased dramatically in the last few decades. There are many additional reasons for this, but clearly leptin is integral.

We must have a healthy dietary lifestyle with nutrient-dense foods, not calorie-rich foods and appropriate meal timing as per the Five Rules of The Leptin Diet. We must find ways to reduce inflammation to stop the vicious cycle of fat cells releasing leptin that directs release of more cytokines which increases inflammation. Nutrients like green tea extract, panax ginseng, ashwagandha, curcumin, DHA and berries (cranberries, bilberry, etc.) help interrupt this process. Melatonin coupled with these nutrients may add another layer of support for autoimmune dysregulation. Many other nutrients help support leptin and reduce inflammation as well.

Rebalancing leptin and turning off inflammation has many different layers of needs and necessary support. When it is out of balance, it is like turning a ship around. It takes time, effort, and work, but it can be done. If the ship is not turned around when in a storm, then it becomes a task of managing the storm damage and trying to prevent the ship from sinking. Are you the captain of your leptin-autoimmune ship?