Leptin: Critical Weight Loss Hormone

 

I commonly have especially women coming in for acupuncture asking for help with weight loss. My heart often sinks when I get asked this question, because acupuncture and herbs, while they can support healthy digestion, metabolism, thyroid function and stress reduction--all of which can be contributing factors to weight gain--are simply not a “magic bullet” for weight loss. Weight loss is surprisingly complex. It can be a slippery slope for so many women, and a constant cause of stress and frustration.

Many women who come in have tried all sorts of diets; indeed, some barely eat anything and still cannot lose weight! Most have had their thyroid tested, and many come back in the clear. (However, the thyroid is a whole topic unto itself; please refer to my article on the thyroid to learn more about how most conventional thyroid testing parameters are grossly insufficient. Balancing your thyroid CAN be a great support for weight loss if done correctly.)

As an extreme case in point, I recently had a patient who over a decade ago had gastric bypass surgery. Since that time, she has not been able to consume more than several hundred calories of food a day and suffers from chronic malnutrition. Despite feeling she should look like a matchstick on a diet that would rival that of a prisoner of war camp, she still wrestles with some excess pounds. She finally made her way to a gastroenterologist who told her that gastric bypass surgery can lead to a chronic back up of fecal matter in the bowels, which then is slowly absorbed by the body over weeks and months, leading to excess weight!

Extremes aside, one of the key hormones likely involved in this frustrating inability to lose weight, especially in women, is leptin. Discovered in 1994, leptin is a fascinating hormone that can be directly related to body fat and obesity. Scientists believe the leptin hormonal system evolved to prevent humans from overeating or starving--both of which prevent you from surviving in a hostile natural environment.

Leptin is secreted by fat cells, and especially after high carbohydrate meals, and its’ target is the brain (specifically the hypothalamus). When you have enough fat stored (time of feast), abundant leptin tells your brain to stop eating and triggers a higher or more normalized level of calorie burning. On the other hand, when you don’t have enough food stored (time of starvation), the lack of leptin triggers increased hunger, and slows down the calorie burning process. In other words, leptin is the hormonal messenger from fat cells communicating with the brain about how much fat they carry, so that the brain can then titrate our metabolic rates and appetite! Amazing, isn’t it?

Leptin Resistance: One of the key biological contributors to unwanted weight gain

So here is where things get tricky. In a straightforward world, fat cells secrete leptin, and it follows that people who are heavy or overweight would have high levels of leptin. It should be that this would then trigger them to stop eating and/or trigger increased metabolism or fat burning. So what is going wrong?

Leptin is very similar to insulin, the hormone secreted by the pancreas to regulate blood sugar uptake into our cells for energy use. Indeed, the two hormones appear to work in tandem. Like insulin, leptin circulates in the blood, but it also must dock at a receptor site for the brain to know it is there, and react accordingly. When circulating leptin does not dock at receptors, the brain will interpret this as low leptin, no matter how high the leptin content in the blood circulation may be.

When leptin cannot dock at receptor sites properly, a condition called leptin resistance develops. It is this condition that often contributes to a stubborn inability to lose weight “no matter what”. There are several reasons why this resistance may develop. These include long-term overstimulation of receptors (due to prolonged high levels of leptin), the aging process, chronic inflammatory conditions, and biotoxin exposure.

Overstimulation of Receptors

Leptin is created from fat tissue, and rises along with glucose and insulin levels in relation to carbohydrates in meals. Regular consumption of high carbohydrate foods (including processed foods and fast foods) cause regular extreme spikes in levels of insulin and leptin. The receptors get ‘tired’ of leptin constantly ‘knocking’, and shut down or lose sensitivity, exactly the way insulin receptors do in the case of insulin resistance. Like insulin resistance, leptin resistance commonly increases with age, and occurs especially when high carb diets are regularly consumed.

Chronic Inflammation

Like all hormones, leptin actually plays many different roles in the body--not just in regulating appetite and metabolism. Leptin is also a key regulator of the endocrine system and HPA axis (critical to stress management and reproductive health), and directly affects insulin secretion, energy homeostasis, and bone formation. Interestingly, leptin is found in females at much higher concentrations than males, probably because leptin is inhibited by testosterone and possibly promoted by ovarian sex steroids.

But more critical to our discussion here, leptin is a cytokine-like mediator produced in fat cells, which has a strong pro-inflammatory affect on the body’s immune responses. (Cytokines are proteins released by cells that effect communication between cells and cellular behavior; many have either a pro-inflammatory or anti-inflammatory effect on immune system pathways.) Now let’s be clear here. These days we tend to have a negative association with inflammation. But inflammation is an important part of the body’s immune and healing responses; you require inflammation in order to heal from an infection. The problem comes when the inflammation is not self-inhibiting, or when it either gets out of control or cannot stop itself.

Studies show that serum leptin levels (in the blood) directly correlate with levels of inflammation in the body! In mice studies, levels of leptin in the blood and fatty tissues typically increase after the administration of an inflammatory stimulus. This can be observed in human subjects when the concentration of leptin is elevated, for example, during active disease in RA patients, and decreases when the disease is controlled. Elevated circulating leptin levels appear to contribute to the low-grade inflammatory background that makes individuals more susceptible to developing degenerative disease, such as cardiovascular disease, type II diabetes, autoimmunity and cancer.  

When a person is in a state of acute or chronic inflammation, many types of pro-inflammatory cytokines are released, not only leptin. These cytokines then easily fit into and attach to leptin receptors, essentially competing with them. When this happens, the brain registers low levels of leptin (although high levels are circulating) and of course this leads to inevitable weight gain. Many people experience themselves caught in a low level inflammatory state, that can then lead to a slow and insidious weight gain. Gaining the upper hand on the inflammation could help these individuals to finally be able to lose the weight, and of course gain a better state of health in the process.

A number of studies have connected leptin in the pathogenesis of autoimmune illness, including type I diabetes, irritable bowel disease, and RA. Studies show leptin can promote auto-reactivity. On the other hand, leptin deficient mice have shown resistance to the development of autoimmune disease. In light of this, it is interesting to note that there is a much higher prevalence of autoimmune disease in females than males, with regard to their higher levels of leptin.

But what about genetics? It appears that genetics can play a powerful role in how leptin plays out (or doesn’t play out) in the body. Mice studies have revealed that obese mice can carry a mutation of the gene that encodes leptin, while other mice are deficient in the gene that encodes the leptin receptor. Both groups of mice have a lack of the perception of satiety (appetite satisfaction), together with hyperglycemia and insulin resistance. Administration of leptin directly can help the first group, but not the second. This makes sense, because once again, if you don’t have the receptors for leptin, your brain interprets this as a low level of leptin no matter how much leptin is circulating in your blood. This genetic connection helps us to understand why some people are born with a tendency to weight gain that appears to defy all dietary attempts.

On the flip side, starvation (or severe reduction in nutrients) will reduce leptin, and coincidentally appears to reduce the inflammatory response. This could be why popular current diets such as the ketogenic diet, or intermittent fasting approaches, with their nutrient restriction, and especially carbohydrate restriction, are so remarkably effective in lowering inflammatory blood lab markers such as C-Reactive protein, in reducing inflammatory symptoms, and of course in promoting natural weight loss.

Leptin and Biotoxin Illness

What is biotoxin illness? Also called CIRS, or Chronic Inflammatory Response Syndrome, biotoxin illness is usually caused by exposure to water damaged buildings, or buildings with a history of water leakage. Since it is estimated that over 50% of buildings in the US have sustained water damage, this includes a good amount of exposure for many. The air in a water damaged building is contaminated by a “chemical soup” of molds, bacteria, and associated chemicals such as VOC’s. But biotoxin illness can also include those exposed to toxins via a tick bite from Borrelia burgdorferi, the organism responsible for Lyme disease, from a brown recluse spider bite, or even exposure to tropical fish that are contaminated with ciguatera toxin, from Pfiesteria and cyanobacteria.

Certain genetics make about 25% of the population more vulnerable to biotoxin illness, rendering them unable to clear the toxins from their system, and thus condemning them to a slow build up of toxins in the body that lead to a chronic acute state of inflammation with a wide range of multi-system health issues. Specific lab testing with a qualified CIRS-trained professional is required for a diagnosis, and a very specific, staged protocol is then required for effective treatment.

Biotoxin exposure causes inflammation, and as we discussed above, this produces a boatload of inflammatory cytokines. These inflammatory cytokines then fit into and block leptin receptors, preventing leptin from docking. Leptin levels then rise in the blood, but the brain does not respond by increasing metabolism and suppressing appetite, because the receptors are blocked. Instead, a slow, insidious weight gain ensues.

It’s important to mention biotoxin illness, as many people may be entirely unaware that they have this condition. If you are experiencing a variety of chronic inflammatory symptoms together with weight gain, and if you know that you might have been exposed to the toxins listed above, then it is vital that you get this condition checked out and treated. Most doctors are unfortunately unaware of CIRS or biotoxin illness, so you will need to search out a qualified health professional to work with. Autoimmune illness is also a common result of CIRS, and I would especially recommend that anyone diagnosed with an autoimmune illness who may have a history of exposure to the toxins listed above, get tested!

Leptin and Melanocyte Stimulating Hormone (MSH)

Along with leptin resistance, when circulating leptin is not docking at receptors, the brain also stops producing a hormone called Melanocyte Stimulating Hormone, or MSH. MSH is a critically important hormone needed for: ADH (Anti-Diuretic Hormone) production to hold urine, melatonin production for sleep, endorphin production for pain management, lubrication of the digestive tract and protection of mucosal surfaces, protection of skin, and sex hormone production.

Symptoms such as frequent urination, nighttime urination, insomnia, increased pain levels, leaky gut symptoms, and hormonal imbalances can then follow. With a significant percentage of the population suffering from these symptoms, together with weight gain unresponsive to diet and exercise, you can see why it is so important to get a handle on the causes driving our leptin production and receptor response.

Fortunately, we can check leptin, MSH, ADH, and a variety of inflammatory markers such as C-reactive protein with some basic lab testing that will help reveal the level of inflammation our bodies are in, and the effect that this inflammation is having on a systemic level.

How to Reset Leptin: Plug all the holes in the dam!

To recap, leptin is a critical hormone used by the brain to ensure our survival. We must work with this system, not against it, to restore sensitivity, and a healthy weight. Obviously, if you suspect exposure to biotoxins, you need to get the lab testing done. A great website for more information Is Surviving Mold, which elucidates the Shoemaker Protocol in the treatment of CIRS if diagnosed.

Likewise, if you have low grade inflammation going on from other causes, it is important to ferret out these causes and address them, whether they be chronic food sensitivities, environmental allergies, or other types of toxic exposures such as heavy metals, pesticides or heavy plastic use. Going on a low carbohydrate diet, and potentially combining it with intermittent fasting (resource listed below), can be an effective way for many to reset their leptin levels. Here at DCA we have guidelines for a Leptin Reset Diet, complete with food recommendations. Feel free to print it out and hang it on your fridge!

For some, losing weight is as simple as cutting back on calories and exercising more. For others, weight loss is a lot more complicated. Regardless, there ARE solutions. The solutions may involve some detective work, but if you have the will, there is a way. Here at DCA, we support you on your journey.

 

Resources:

Pubmed article "Leptin and Inflammation"
The Complete Guide to Fasting by Jason Fong MD, and Jimmy Moore


 

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