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)

Leptin: the obesity hormone released by mast cells

Leptin is a hormone that is primarily secreted by adipose tissue, but is also produced and released by mast cells. In turn, mast cells also have leptin receptors. Leptin is primarily known for its action of part of the hypothalamus to inhibit the hunger response. Importantly, the body responds forcefully to leptin levels by engaging both biological and behavioral mechanisms to conserve energy. It is seen by researchers as less of a “hunger satiety” signal and more of a “starvation” signal.

Patients with obesity often have higher circulating levels of leptin than those without obesity. This occurs because leptin is secreted by adipose tissue, which obese patients have in higher amounts due to their higher percentage of body fat. These people seem to be resistant to the chemical action of leptin, possibly through a change in activity of leptin receptors in the hypothalamus. Some studies suggest that in obese patients, less leptin leaves the blood stream and crosses into the brain.

Leptin is now known to have a variety of other effects on the body, including modulating the immune system. It activates inflammatory cells, promotes T cell responses and mediates production of TNF, IL-2 and IL-6. In many inflammation models, cells express more leptin receptors than usual. In diet induced obese mice, mast cells have been observed to store and secrete TNF. In immune mediated diseases like autoimmune diseases, circulating levels of leptin are increased, and this in turn translates to higher levels of inflammatory cytokines.

Interestingly, leptin suppresses signals from the IgE receptor to make mediators. In leptin receptor deficiency models, magnified IgE anaphylaxis was observed. Leptin also seems to control the number of mast cells through some unclear mechanism. In leptin deficient mice, mast cell density is significantly higher in abdominal lymph nodes and fat deposits.

Leptin influences the release of many other molecules, including ghrelin. Ghrelin is the “hunger hormone,” released in the stomach and possibly elsewhere. It stimulates the hunger response in the body and also acts on the hypothalamus. The relationship between leptin and ghrelin is very complex and still being elucidated. However, it is thought that high levels of circulating leptin suppress secretion of ghrelin. This is especially of interest in inflammatory conditions as ghrelin suppresses production of a number of inflammatory markers, including TNF, IL-8, MCP-1, IL-1b, IL-6, CRP and others. This effect is so pronounced that it is being investigated as a treatment option for many conditions. Ghrelin has also been observed in one study in induce mast cell activation through a receptor independent pathway.

 

References:

Baatar D, Patel K, Taub DD. The effects of ghrelin on inflammation and the immune system. Mol Cell Endocrinol. 2011 Jun 20; 340(1): 44-58.

Hirayama T, et al. Ghrelin and obestatin promote the allergic action in rat peritoneal mast cells as basic secretagogues. Peptides. 2010 Nov;31(11):2109-13

Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007 Jan; 8(1): 21-34.

Taildeman J, et al. Human mast cells express leptin and leptin receptors. Histochem Cell Biol. 2009 Jun; 131(6): 703-11.

Patricia Fernández-Riejos, Souad Najib, Jose Santos-Alvarez, Consuelo Martín-Romero, Antonio Pérez-Pérez, Carmen González-Yanes, and Víctor Sánchez-Margalet. Role of Leptin in the Activation of Immune Cells. Mediators of Inflammation, Volume 2010 (2010), Article ID 568343, 8 pages.

Altintas et al. Leptin deficiency-induced obesity affects the density of mast cells in abdominal fat depots and lymph nodes in mice. Lipids in Health and Disease 2012, 11:21

Fat

Once I hit puberty, I was a fat girl.  I wasn’t morbidly obese, but I was overweight and it was obvious on my short frame.  This was not something I hated about myself, and it wasn’t until college that I felt uncomfortable with my body, but it informed my later years.  The experience of being overweight (and therefore mocked/ridiculed/generally viewed as “unfortunate” or “unseemly” or “lazy”) has affected my ongoing relationship with myself.
In 2007, I lost 40 lbs by training for the Breast Cancer 3-Day.  I also lived alone and worked a lot, on my feet.  I was committed to training, but also still had the privilege of a largely functioning body.  I was tired and had some joint issues, but it was more occasionally annoying than anything else.  Most importantly, I had time and stamina.  I could walk 10 miles a day, in the sun, in the heat, without any fallout. 
My weight fluctuated a little bit for the next few years, until in 2009, when I lost my hearing.  My neurotologist wrote out a long, high dose steroid taper and within a month, I had gained over 20 lbs.  In 2012, after a serious effort (working out 6-8 hours a week for several months), I lost 10 of those pounds. 
This was the point at which I realized that there was some fuckery afoot with my weight.  Like no matter what I ate, or how much I exercised, my body would not lose any more weight, and especially not around my swollen midsection.  A few months later, I had my ostomy surgery and in the weeks after that, I lost 10 more pounds.  The swelling and squishiness was gone.  The proof was in the pudding.  My mast cell disease and its subsequent inflammation were keeping me swollen, and squishy, and fat. 
Fast forward several months and a prescription for high dose steroids was being slid across the desk to me.  “I don’t want to do this again,” I started, but I knew I basically had no other play.  So I took them.  And two months later, I had gained thirty pounds. 
I am still on steroids; very low dose, but still on them.  As I have stepped down the steroids, I have lost some weight, but I am still 20 lbs over where I was.  I walk a lot (10-15 miles a week), and do yoga as I’m able, but my body has taken a serious beating this year.  I got a PICC line placed in March, which meant no weight bearing with that arm, and that eliminated most strenuous forms of exercise I can safely do.  I can’t do cardio.  I couldn’t swim with the PICC.  Now I have a port, and I can’t do any exercise for at least five days.  I’m forever being told not to exert myself while also being reminded that being overweight causes me a lot of problems. 
I have almost no control over the way my body looks.  I don’t mind having a colostomy and a port, I really don’t.  But I do mind that being overweight means that people judge me for being “lazy” or “unhealthy” or “making bad choices.”  I don’t know why anyone would ever comment on a person’s diet or general fitness, but it happens to me, so I’m sure it happens to you.  People are always like, “Oh, anyone can do [insert name of cliché fitness trend],” or “Your problem is that you drink soda,” or whatever. 
Are you kidding me, people?
Are you fucking kidding me?
I think my problem is that I have a rare, severe, life threatening disease that is destroying my body.  I think that’s my problem.
I cannot eat your stupid diet food because it’s full of artificial sweeteners and garbage.
I cannot do cardio because it will cause me anaphylax. 
I cannot do most other types of exercise because my body fucking sucks and has failed me repeatedly.  And the fact that it is fat is the least of the ways it has failed me. 
I throw up a lot of what I eat.
I drink one can of Coke a day.  I will probably do this every day until I die.  And you know what?  That’s 140 calories my body needs, because while you’re thinking about how much less I should be eating, I am not getting the amount of calories or vitamins or minerals that my body needs.  And frankly, for all the shit I have to put up with on a daily basis, a can of Coke is the least of what I deserve.
I don’t like being inactive.  I don’t like lying in bed and needing to sit frequently.  I don’t like feeling weak. 
There are some days when I look in the mirror and think that can’t be me.  I am so tired of living in this shell that doesn’t even look like me.