The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 51

63. Why do many mast cell patients gain weight? Why can’t they lose it?

The most common question I get about weight is “Why am I gaining weight when I can barely eat?” Weight gain, or failing to lose weight, is not unusual for mast cell patients. There are a lot of reasons why this happens.

One of the big reasons why mast cell patients gain weight is because mast cells release molecules that cause inflammation. Some of these molecules are known to be linked to obesity when there is too much of them in the body. Mast cells release some of these molecules, like TNF, and IL-6.

Leptin is a hormone released by mast cells that can contribute to obesity. Patients with obesity often have higher than normal levels of leptin in their blood. In these patients, it seems like leptin doesn’t work as well as in others, so their bodies need to make more leptin.

Leptin’s job in the body has long been thought to tell your brain that you are not hungry. More recent research suggests that leptin doesn’t exactly tell your brain that you’re not hungry, and instead tells your brain that your body is starving. The body responds to this “starving” signal very strongly by trying to maintain or gain weight, and to maintain or gain fat stores.

Mast cells live in adipose tissue (fat tissue), often in significant numbers. Leptin level somehow controls the amount of mast cells in adipose tissue (fat tissue) but we are not sure how. Leptin is one of the ways that mast cells tell other cells to become inflamed. It tells cells to make more inflammatory molecules like TNF, IL-2 and IL-6. Mast cells in inflamed spaces can also attract cells from other parts of the body to come and make more inflammation.

Leptin also directly opposes another hormone, ghrelin. Ghrelin is the hormone that tells your brain that you are hungry. When leptin is high, ghrelin is low. Importantly, ghrelin curbs inflammation and tells cells to stop making inflammatory molecules. If leptin is high, ghrelin is not around as much to stop inflammation.

Another way mast cell disease can contribute to weight gain is by swelling. When mast cells are activated, they release molecules that make it easier for fluid in the bloodstream to “fall out” of the bloodstream and get stuck in tissues. When this fluid is stuck in the tissue, your body can’t just pull back into the bloodstream. It takes days for your body to be able to get the fluid out of the tissues and back into a place where it can be used.

Some of the medications used to treat mast cell disease can cause weight gain. H1 antihistamines are probably the drugs most commonly used for mast cell disease. They can cause weight gain. Steroids like prednisone and methylprednisolone cause swelling and weight gain.

Mast cell patients often have difficulty maintaining a normal sleep schedule. Sleep at night is often not restful because mast cells are very active at night. Not sleeping well can cause inflammation, contributing to weight gain.

Exercise can be very tricky for mast cell patients as well. Many patients are deconditioned and out of shape so even low impact exercise can be exhausting or impossible. Mast cell patients often have restrictions on what exercises they can do safely so vigorous exercise to help regulate weight might not be an option.

Mast cell patients often have little control over their diet due to food reactions, reacting to the process of eating, or having other GI conditions like gastroparesis. Safe foods may not be “healthy” and can contribute to weight gain. (Potato chips are a huge part of my diet as a food that is always safe for me.)

I personally struggled with my weight for years as a result of mast cell disease. It has been my experience that reducing inflammation overall is the only way to lose weight. Of course, it is very difficult to reduce inflammation when you have mast cell disease. In my case, I found that a reconditioning program helped me immensely. This is not safe for everyone and you should never start an exercise program without discussing it with the provider that manages your care.


For more detailed reading, please visit the following posts:

Leptin: the obesity hormone released by mast cells
Exercise and mast cell activity
My exercise program for POTS and deconditioning
Deconditioning, orthostatic intolerance, exercise and chronic illness (Part One)
Deconditioning, orthostatic intolerance, exercise and chronic illness (Part Two)
Deconditioning, orthostatic intolerance, exercise and chronic illness (Part Three)
Deconditioning, orthostatic intolerance, exercise and chronic illness (Part Four)
Deconditioning, orthostatic intolerance, exercise and chronic illness (Part Five)
Deconditioning, orthostatic intolerance, exercise and chronic illness (Part Six)
Deconditioning, orthostatic intolerance, exercise and chronic illness (Part Seven)

Interplay between mast cells and hormones: Part 5 of 8

Hormone Location released Major functions Interaction with mast cells Reference
Inhibin Testes, ovaries, placenta, pituitary Inhibits production of FSH No known interaction with mast cells
Insulin Pancreas Promotes transfer of glucose from blood to liver and muscle

Promotes production of glycogen in liver

Promotes liberation of glucose stores in liver

Increases growth and survival of mast cells

Increases degranulation and mediator release

Lessmann E, et al. Insulin and insulin-like growth factor-1 promote mast cell survival via activation of the phosphatidylinositol-3-kinase pathway. Experimental Hematology 2006: 34(11), 1532-1541.
Insulin like growth factor Liver Modulates cell growth and development

Behaves like insulin

Increases growth and survival of mast cells

Increases degranulation and mediator release

Lessmann E, et al. Insulin and insulin-like growth factor-1 promote mast cell survival via activation of the phosphatidylinositol-3-kinase pathway. Experimental Hematology 2006: 34(11), 1532-1541.
Leptin Adipose tissue Decrease of appetite Activates inflammatory cells and T cell responses

Increases production of TNF, IL-2 and IL-6

Decreases mediator production due to activation of IgE receptor

Suppresses secretion of ghrelin

Taildeman J, et al. Human mast cells express leptin and leptin receptors. Histochem Cell Biol 2009: 131(6), 703-711.
Luteinizing hormone (LH) Pituitary Stimulates ovulation and formation of corpus luteum

Stimulates testosterone production

Histamine decreases LH release by acting at H1 receptor.

Histamine increases release of luteinizing hormone releasing hormone (LHRH), also by acting at H1 receptor.

Miayke A, et al. Involvement of H1 histamine receptor in basal and estrogen-stimulated luteinizing hormone-releasing hormone secretion in rats in vitro. Neuroendocrinology 1987: 45(3), 191-196.

Pontiroli AE, et al. The effect of histamine and H1 and H2 receptors on prolactin and luteinizing hormone release in humans: sex differences and the role of stress. J Clin Endocrinol Metab 1981: 52(5), 924-928.

Melanocyte stimulating hormone (MSH) Pituitary Stimulates melanin production and release

Increases during pregnancy

MSH can induce apoptosis in mast cells

Dose dependent increase in histamine relief, but not in IL-1, IL-6, IL-8, TGFb or TNF

Sarkar A, et al. alpha-Melanocyte-stimulating hormone induces cell death in mast cells: involvement of NF-kappaB. FEBS Lett 2003: 549(1-3), 87-93.

Grutzkau A, et al. alpha-Melanocyte stimulating hormone acts as a selective inducer of secretory functions in human mast cells. Biochem Biophys Res Commun 2000: 278(1), 14-19.

Melatonin Pineal gland, immune system Induces sleep and lowers body temperature Mast cells produce and release melatonin regardless of activation state Maldonado MD, et al. Evidence of melatonin synthesis and release by mast cells. Possible modulatory role on inflammation. Pharmacol Res 2010: 62(3), 282-287.


Exercise and mast cell activity

Research on exercise induced bronchoconstriction represents a large body of work through which we can draw conclusions about mast cell behavior as affected by exercise.

Exercise has been found in a number of studies to induce mast cell degranulation and release of de novo (newly made) mediators. One study found that levels of histamine, tryptase and leukotrienes were increased following exercise in sputum of people with exercise induced bronchoconstriction. This same study found that in these patients, prostaglandin E2 and thromboxane B2 was decreased in sputum. Treating with montelukast and loratadine suppressed release of leukotrienes and histamine during exercise.

One important area of research is the interface between being asthmatic and being obese. Adipose tissue is known to release inflammatory molecules called adipokines. In particular, the adipokine leptin has been studied for its role in bronchoconstriction following exercise. Leptin (I did a previous post on leptin, which is also called the obesity hormone) enhances airway reactivity, airway inflammation and allergic response. It can also enhance leukotriene production. This last fact is interesting because obese asthmatics are less likely to respond to inhaled corticosteroids when compared to lean asthmatics, but both respond similarly to anti-leukotriene medications like montelukast.

LTE4 was found to be significantly higher in the urine of both obese and lean asthmatics following exercise. It was not increased in either obese non-asthmatics or healthy controls. Additionally, the level of LTE4 was significantly higher in obese asthmatics compared to lean asthmatics. In this same study, urinary 9a, 11b-PGF2 was elevated in both lean and obese asthmatics, but not in obese or healthy controls. The 9a, 11b-PGF2 level was also higher in obese asthmatics than lean asthmatics. The elevated LTE4 and 9a, 11b-PGF2 were found in urine testing rather than in sputum, indicating that these chemicals did not stay local to the lungs and airway.

It is thought that the high levels of leptin found in asthmatics drive the manufacture and release of leukotrienes and prostaglandins from mast cells, epithelial cells or eosinophils during exercise. Though the data are stacking up to look like this is the case, there has not yet been a definitive causal link established.



Teal S. Hallstrand, Mark W. Moody, Mark M. Wurfel, Lawrence B. Schwartz, William R. Henderson, Jr., and Moira L. Aitken. Inflammatory Basis of Exercise-induced Bronchoconstriction. American Journal of Respiratory and Critical Care Medicine, Vol. 172, No. 6 (2005), pp. 679-686.

Hey-Sung Baek, et al. Leptin and urinary leukotriene E4 and 9α,11β-prostaglandin F2 release after exercise challenge. Volume 111, Issue 2, August 2013, Pages 112–117