Malfunctioning Immunity Causes Weight Gain – The Leptin Diet Weight Loss Challenge #4

Monday, April 23, 2012
By: Byron J. Richards,
Board Certified Clinical Nutritionist
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I am entering a new term into the lexicon of the weight loss world – metabolic flu.  The primary symptom of this problem is abnormal fatigue.  This includes feeling like you did not sleep well, easy power outages by mid-afternoon, and erratic energy at night that is a bizarre combination of fatigue and wired energy that often results in sleep problems. This type of fatigue is also associated with difficulty getting energy from a reasonable amount of food and an inability to sustain energy between meals without snacking. 

Any person who is not able to lose weight and feel better by simply following the Five Rules of the Leptin Diet, eating higher quality food, and getting consistent exercise has some degree of metabolic flu. Many times this issue is cleared up by following the basic guidelines I have given in the articles on The Leptin Diet Weight Loss Challenge.  However, as fatigue increases, metabolic flu flares up.  It is safe to say that serious metabolic problems, such as fibromyalgia and hypothyroidism, have metabolic flu making these problems worse and quite possibly are the primary cause of such issues.

I do not use the term metabolic flu lightly. It is truly a malfunction and inefficiency of your immune system that impacts your metabolism. It makes you more at risk for getting sick with an infectious bug and more at risk for cancer. It also underlies asthma and allergy, and is a major factor in autoimmune problems of almost every type. Not managing this problem as the years go by leads to metabolic syndrome X, meaning high blood pressure, high cholesterol, high triglycerides, high blood sugar, and risk for type 2 diabetes, cardiovascular disease and early onset of cognitive decline. 

In other words, metabolic flu, while a new term, is of the utmost importance to your quality of health.

How Leptin and Immunity Promote Survival

Leptin is the key hormone in your body that enables your survival, as it is the hormone that permits your body to spend energy. Since energy is needed for everything your body does, its fundamental importance cannot be overstated.

For example, leptin signaling to your subconscious brain following a meal gives you a full signal and sends the subconscious message that you have been to the gas station. You now have plenty of fuel in your tank, and it is time to kick your energetic systems into gear. That is an example of a central regulatory system in your body that sets your overall energy spending policy.

In the past few years, scientists have demonstrated that every single immune cell in your body has receptors for leptin1 and many of these immune cells can actually make leptin2.  Why does your immune system do that?  It doesn’t have anything to do with your full signal following a meal.  Understanding this discovery is of the utmost importance if you wish to understand why you may be struggling with your weight.

During evolution, the two greatest threats to survival were food scarcity and infection. While leptin manages your overall metabolism, it wears a General’s clothing.  Both leptin and the receptors for leptin are structured as components of your immune system (cytokines), which turns out to be far more than a germ defense system.  In fact, it is a primary communication system in your body that doles out how your energy is to be spent as well as how your body repairs itself.

Your immune system requires tremendous amounts of energy when it is challenged by a foreign invader.  During evolution, it was not uncommon that a person could become infected with something during a period of food scarcity.  This poses a paradox: how will you have enough energy to fight the infection when your body is trying to conserve energy due to potential starvation?

Leptin’s general function in your body, once it communicates via leptin receptors, is to turn on gene signals involved with DNA activation (JAK-STAT pathway).  For example, when leptin binds to the receptor for leptin on the surface of an immune cell, this leptin message is transduced into the immune cell and acts to turn on energetic genes within the immune cell. The leptin message does not tell the immune cell why it is being energized.  It is simply stepping on the immune cell’s gas pedal.

Immune cells have multiple other receptors. Various substances binding on to the other receptors give the immune cell the information it needs to perform appropriate actions based on what is going on. It may be a bacterial infection, a viral infection, a sprained ankle, or some other issue.  How your immune cells interpret all the information coming to them is very complex3 and far from understood – it is actually the modern frontier of science.  What we do know is that immune cells have local intelligence, they are energetically activated by leptin, they will take action based on other signals coming to them, and immune cells activities and metabolism are highly linked together4.

Furthermore, many immune cells also produce leptin, which then goes to other immune cells and activates them, which sustains an energetic immune response5.  This is how your body solved the evolutionary problem of having enough energy to mount an immune response even when food was in short supply. 

It is interesting that leptin is also secreted by digestive tract cells following a meal, which is not directly related to your overall full signal. Rather, it is giving the immune cells lining your digestive tract and in the surrounding lymphatic tissue a heads up and turning them on – so as to protect you from any infectious agent that may have been consumed along with the food.

The issues I am describing regarding leptin and immune cells are true genetic settings that have taken tens of thousands of years to establish.  Importantly, this system learned to perform in an environment of food scarcity. You are much less likely to have the metabolic flu when you eat less food than the amounts typically consumed by Americans today. 

What is Metabolic Flu?

Metabolic flu is the inappropriate and chronic activation of your immune system6 cells, malfunctioning in a way that promotes weight gain and makes weight loss difficult.  I will explain this first in the context of leptin resistance and then explain step-by-step how someone goes from being normal weight to being overweight, and finally what you need to do to solve the problem.

Leptin resistance means that your white adipose tissue is making too much leptin and for a variety of reasons the leptin signal is not easily getting into your brain or registering in it. This is what I call a false state of perceived starvation.  Your body thinks it is starving and so must keep eating, even though you are far from starving. In other words, the problem of leptin resistance means you don’t have enough leptin in your brain in relation to eating a normal amount of food. On the other hand, you have too much leptin in your blood stream. Therein lies the problem.

The excess leptin chronically and inappropriately activates immune cells. The net result is excessive inflammation with concurrent lack of normal energy (a person is often anxious or wired).

The path from normal weight to overweight is indeed an interesting one. A normal weight person eating too much in violation of the Five Rules of the Leptin Diet will start to feel fatigue or not as energetic as usual. This is a first symptom of trouble, before any weight is even gained. Eating a high fat/high sugar diet7 induces changes to immune cells that set the stage for obesity risk. This type of diet is also known to create imbalances in the digestive bacteria, as would antibiotics. I explain this fully in my second article in this series, How Digestive Problems Prevent Weight Loss.

It appears that a recipe of problems needs to coexist with the stress of a poor diet in order to really set weight gain in motion. The combination of toxic LPS from digestive imbalance, changes to immune cell populations, and higher circulating leptin is the fast track to gaining weight. A new study shows that when these changes in immune cells are combined with toxic LPS8, a ramped up inflammatory response occurs that sets weight gain into motion.  Such excessive leptin and immune activity could also be triggered by toxins. The toxin issue is explained in my article, Why Toxins and Waste Products Impede Weight Loss.  So this is the combination of factors that gets the inflammation going.  It is now clear that the immune cells9 within white adipose tissue, as well as the toxic LPS and environmental toxins, are all directly stimulating the expansion of white adipose tissue10 and weight gain.

Once this combination of problems starts, the metabolic flu begins to ramp up and lock itself into place. The inflammation within white adipose tissue activates monocytes that go out into your circulation and recruit more macrophages to come to your white adipose tissue. Interestingly, this appears to be a self-defense mechanism against being poisoned by too much food. The macrophages are actually trying to liberate the fat from the fat cells using a highly inflammatory backup strategy. Unfortunately, their last ditch effort is overwhelmed by even more calories coming in that must be stored as fat. We now have excessive inflammatory macrophage activity locked into place, worsening in direct proportion to the expansion of your waistline. The inflammation in your white adipose tissue enters your general circulation and induces wear and tear, causing you to feel tired.  One of your genetic responses to tiredness is eating to get energy – and around we go in a vicious circle of progressively worsening health, i.e., metabolic flu.

It must be understood that the immune cells involved with this problem are the same immune cells you use to fight infection, knock out cancer cells, and regulate the efficiency of your immune functions (the lack of autoimmune issues). Metabolic flu induces malfunction in the other duties of your immune system.

Immune cells work best when they go from a resting to an active state when needed. Metabolic flu chronically activates immune cells; they get tired and resistant to leptin signaling. It is like a repetitive strain injury to immune cells.  Immunity in general starts to malfunction.

For example, the Natural Killer (NK) cells of your immune system need to be in tip-top shape to knock out cancer cells and to kill virally infected cells.  Research now shows that high levels of leptin, the leptin resistance of obesity, cause NK cells to not respond to leptin normally – meaning their energetic activation and consequent ability to do their job is handicapped. In fact, NK cells from normal weight animals responded to leptin activation four times better than NK cells of overweight animals11. This is one mechanism that links obesity to chronic low-grade viral infection as well as increased cancer risk.

Dendritic cells are the bridge between your front line immune troops (innate immunity) and your higher powered immune response (adaptive immunity). They must be properly energized and function well in order to coordinate and sustain an appropriate immune response. Leptin is required for their healthy activation12 and function.

It is quite clear that excessive leptin is at the root of malfunctioning immune cell activity13 with consequent low-grade or high-grade inflammation. This means that all this inappropriate activation of your immune cells can program them into autoimmune behavior.  Excessive surges in leptin signaling14 have been found to trigger the onset of autoimmune problems.

The bottom line is that developing the metabolic flu is what causes you to gain weight in the first place and is clearly locked into place in people who struggle to lose weight. Furthermore, the longer the problem exists and worsens, the more likely it is that other more serious metabolic problems and immune system problems will develop.

Solutions for Metabolic Flu

The Leptin Diet is an eating strategy that is specifically designed to help unravel metabolic flu. If you follow the diet, have great energy and lose weight, then your metabolic flu is dormant. By the time you have lost 15 pounds your metabolic flu is under control for the time being. You must reach a true healthy weight and stay there for one year before the problem is solved, because once you get metabolic flu it is easy to get it again. During that year you are making new metabolically fit fat cells that are adjusted to your current weight, while many of your old unfit fat cells are dying off.

It appears to be human nature that people do really well on the Leptin Diet and then start to get into a pattern of eating too much or getting off track. At first they seem to get away with it. Then their energy starts to suffer as the metabolic flu begins to raise its ugly head. The weight starts to come back and it feels hard to break out of the rut and get back on track.

The basic nutrient guidelines I gave in the first article in this series, The Leptin Diet Weight Loss Challenge #1 – Overview and Basic Needs, contains many nutrient tips that will help improve metabolic flu by improving antioxidant status, reducing inflammation, or improving immune system function. The second and third articles in this series deal with toxic LPS from digestive imbalance and environmental toxins. Improving these issues will directly improve metabolic flu by removing key “ingredients” from the recipe that appear to be required for the activation and prolongation of metabolic flu.

Your metabolic flu is better when your energy is better, you are able to follow the Leptin Diet, and you are actually losing weight. Thus, implementing the strategies I outlined in the first three articles may have already brought the metabolic flu under control. If not, you can take extra steps. These extra steps are higher levels of nutrients that directly turn off inflammation in immune cells within white adipose tissue.  A similar strategy is to take nutrients to boost the primary anti-inflammatory hormone within stored fat known as adiponectin. Boosting adiponectin has been shown to restore efficiency in immune cells15 as well as boost their ability to fight infection16.  And if you are prone to getting sick too easily, then taking extra nutrients to directly help your immune system function better will synergistically help your metabolic flu as well.

As far as one specific nutrient goes, quercetin has been proven to change the immune cell population in white adipose tissue.  I cover this in detail in my article, Quercetin: A Rising Star for Nerves, Immunity, and Metabolism.  Many nutrients have been shown to help reduce inflammation in white adipose tissue, including DHA, green tea, resveratrol17, grape seed extract, mangosteen, blueberries, and tocotrienols.  Many of these same nutrients also boost adiponectin.

Your goal is to have enough immune correcting nutritional support to suppress the excess inflammation within white adipose tissue so that weight loss can be engaged. Sometimes higher amounts of one or more of these nutrients are needed.  If you are lucky, the problem will just snap into shape by strictly following the Five Rules of the Leptin Diet. Once you get on track you will save yourself a lot of time if you simply stay on track.


Read More:  Weight Management News

Referenced Studies:
  1. ^ Leptin Receptors  ur J Med Res.   Gorska E, Popko K, Stelmaszczyk-Emmel A, Ciepiela O, Kucharska A, Wasik M.
  2. ^ Immune Cells Make Leptin to Regulate Themselves  Immunity.  De Rosa V, Procaccini C, Calì G, Pirozzi G, Fontana S, Zappacosta S, La Cava A, Matarese G.
  3. ^ Multiple Aspects of Leptin and Immnuity.  Brain Behav Immun  Fantuzzi G.
  4. ^ Leptin Links Metabolism and Immunity  Expert Rev Clin Immunol.  At the crossroad between immunity and metabolism: focus on leptin.
  5. ^ .Leptin Directly Energizes the Immune Response  Gen Comp Endocrinol.   Demas GE.
  6. ^ Leptin’s Central Role in Immunity  Cell Mol Immunol  Lam QL, Lu L.
  7. ^ High Fat and High Sugar Diet Breed Impaired Immune Cells  J Nutr Health Aging.  Sato Mito N, Suzui M, Yoshino H, Kaburagi T, Sato K.
  8. ^ Leptin Combined with LPS Turns Macrophages Inflammatory  Mol Immunol  Vaughan T, Li L.
  9. ^ Lymphocytes Underlie Adipose Tissue Inflammation and Abnormal Growth  J Physiol Biochem.  Caspar-Bauguil S, Cousin B, Bour S, Castiella L, Penicaud L, Carpéné C.
  10. ^ Immune-Related Inflammation in White Adipose Tissue Stimulates Growth of Tissue  J Immunol.  Alexaki VI, Notas G, Pelekanou V, Kampa M, Valkanou M, Theodoropoulos P, Stathopoulos EN, Tsapis A, Castanas E.
  11. ^ Leptin Signalling and Natural Killer Cells  Endocrinology  Nave H, Mueller G, Siegmund B, Jacobs R, Stroh T, Schueler U, Hopfe M, Behrendt P, Buchenauer T, Pabst R, Brabant G.
  12. ^ Leptin Influence on Dendritic Cells  Eur J Immunol.   Fantuzzi G.
  13. ^ Leptin Problems Generate Pathogenic Levels of Inflammation  Mediators Inflamm.  Fernández-Riejos P, Najib S, Santos-Alvarez J, Martín-Romero C, Pérez-Pérez A, González-Yanes C, Sánchez-Margalet V.
  14. ^ Excess Leptin Involved with AutoiImmmune Response  J Clin Invest.   Sanna V, Di Giacomo A, La Cava A, Lechler RI, Fontana S, Zappacosta S, Matarese G.
  15. ^ Adiponectin Restores Natural Killer Cell Function in Obese Humans  PLoS One.  O’Shea D, Cawood TJ, O’Farrelly C, Lynch L.
  16. ^ Adiponectin is Needed for Healthy Immune Response to Infection  Cytokine.  Sashinami H, Nakane A.
  17. ^ Quercetin, Genistein, and Resveratrol Inhibit Fat Cells.  J Med Food.  Park HJ, Yang JY, Ambati S, Della-Fera MA, Hausman DB, Rayalam S, Baile CA.

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