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Leptin: The Weight- and Energy-Balance Hormone

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From The Mitochondriac Manifesto.

Leptin is the master hormone that influences all energy production and usage in the body, including psychological programming affecting motivation and activity. It’s the once-mysterious force that controls programs, processes, and perplexing conditions even the most renowned healers in history could never explain before.

Like a concert conductor, leptin controls the activity of all the hormones used by the digestive system, adrenals, brain and reproductive organs… in order to regulate your weight, resting “idle speed,” immune function, fertility and emotional state. Yet most people know nothing about it, having just been discovered in 1994.

How the leptin system regulates body weight

The endocrine system uses leptin level in the blood to adjust your appetite up or down so your weight stays as stable as possible. The way it works is simple: The hormone leptin is made by subcutaneous fat cells in proportion to a person’s total fat mass. The more leptin that leptin receptors in the hypothalamus find circulating in the bloodstream at night, the more it suppresses appetite. The less they find, the more your appetite increases. So through this feedback and control mechanism, fat mass is designed to regulate not just how much you eat, but also how much energy you use.

More specifically, the presence of body fat and leptin should give you an earlier, and stronger, sensation of fullness when you eat in order to encourage you to lose weight. Conversely, the absence of body fat and leptin should make you more hungry, more often, in an effort help you get to your ideal weight. At least, that’s how it’s supposed to work. However, we now realize through our understanding of how leptin works that this feedback-control mechanism is malfunctioning in many people, breeding rampant obesity, adrenal dysfunction, diabetes and fertility problems, among other conditions so common we consider them normal.

To help you understand the biological programming behind these breakdowns, when leptin receptors in your hypothalamus are unable to see how much leptin is in your system – because of leptin resistance – your body thinks it’s starving. So, like a car with a broken gas gauge, it makes you fill up more frequently than you really need to by increasing your appetite prematurely… just to be on the safe side.

Equally problematic, the endocrine system lowers thyroid function, the immune system, insulin signaling, and reproductive function in order to conserve energy for higher priorities. Your mental and emotional states are depressed to discourage activities that burn energy. Leptin resistance (i.e., when the system is under-performing) basically creates a starvation response in people by chronically activating all sorts of adaptive mechanisms to cope with the perceived energy shortage. It down-regulates organs, processes, and behaviors to conserve energy. That spells disorder all over the body.

Bottom line: Leptin isn’t the only mechanism that regulates body weight. But it is the most important one, because it’s the master controller that uses its executive powers to manage a wide range of essential processes throughout the body. That means leptin is commander-in-chief of weight maintenance. And it operates with impressive influence over bodily functions and programming. So the other systems and processes we thought were responsible for weight gain/loss act subordinately to leptin’s direction. Insulin and thyroid function are but two of leptin’s principal lackeys.

When leptin reception tanks

When you have more fat mass than you need, the leptin system is designed to turn down your appetite (intake), and turn up your thyroid speed (expenditure). The opposite is also true: The less fat mass you have, the more the leptin system encourages you to put on weight by increasing your appetite and decreasing your thyroid function.

Unfortunately, when your hypothalamus is unable to see how much leptin is in the bloodstream – that is, when you lose leptin sensitivity – it can’t tell how much fat mass the body has. This makes you lose the ability to regulate appetite, energy expenditure, and ultimately body mass. Therefore, obesity is primarily a failure of the leptin system to respond to high leptin levels in the blood (>10 ng/ml), while anorexia can be a failure of leptin receptors to recognize low leptin levels (<4 ng/ml). Both are caused by dysfunctional leptin reception spoiling your appetite regulation.

News you can use: When you “wake up” your leptin system from its state of slumber, the body realizes its fat mass is dramatically different than what it thought. It then puts enormous pressure on your energy management systems to get you to your ideal weight. This causes the body to make all kinds of adjustments large and small to get you to eat less, store less, and burn more. And that’s how people are losing staggering amounts of weight in record time using the Leptin Prescription Reset and Cold Thermogenesis Protocols (Dr. Jack Kruse’s protocols).

Internalize this like a mantra: The new, improved road to substantial weight loss is the journey to leptin sensitivity. On the other hand, weight loss without regaining leptin sensitivity is the biggest reason the pounds tend to come back with a vengeance, after a successful diet.

Many people think they have a thyroid problem, when it’s actually leptin resistance

Astoundingly common today, leptin resistance has a nasty habit of turning thyroid function way down. “Hypothyroidism,” as depressed thyroid function is called, can cause symptoms such as extreme fatigue; weight gain; weakness; cold hands, feet and body; hair loss; brittle nails; dry skin; constipation; poor memory; and depression.

In other words, leptin resistance can make you have a “slow metabolism,” give you the appearance of thyroid dysfunction, and make weight loss extremely difficult because your resting calorie consumption is too low. It can even prevent people from losing weight when they exercise, because the metabolic benefits of exercise are not carrying over fully into the resting state. As a result, leptin resistance can cause health practitioners to misinterpret thyroid function tests, because the presence or absence of thyroid hormones may not be the actual cause. Leptin insensitivity may be the real problem – predominately, or as a contributing factor.

Women are more sensitive to leptin, and their environment

Women are built to be more sensitive to biophysical forces around them – temperature, food and EMFs, for instance – than men are. They have to be so that their mitochondria can adjust their metabolism to suit their surroundings. They then pass those survival-enhancing adaptations on to their children in the form of mitochondrial haplotype and heteroplasmy rate, as well as epigenetic changes to nuclear DNA.

Women also average more fat mass than men, on a percentage basis. That means more leptin. The thing is, leptin is pro-inflammatory, having thought to have evolved from interleukin-6 (IL-6), a pro-inflammatory chemical made by the body. That’s how leptin works: leptin from fat creates an inflammatory state (and a signal) that the leptin receptor reads, then tells endocrine organs to either gain weight or lose weight.

Those two factors – chronically higher leptin levels, and greater sensitivity to the environment – put women closer to the edge of having chronic inflammation all the time. It’s in their nature to have a finer line between inflamed and not inflamed. This is a huge reason why women typically gain weight more easily, and have a harder time losing it.

Leptin controls fertility

The leptin system is Nature’s way of picking a good time to have a baby. It does this by monitoring both energy reserves, and energy in circulation, to make sure the body has enough resources to gestate a baby.

If the leptin system senses a woman has enough energy to safely carry a baby to term, it picks an immature egg to develop, and Nature takes its course. When it doesn’t, the leptin system makes her inner terrain inhospitable to pregnancy by delivering eggs of poor quality, irregular menstrual cycles, and reduced receptivity of the uterine lining.

Leptin level is supposed to control this process. However, when leptin receptors aren’t responding properly to leptin in the system, the endocrine system blocks reproductive processes. Couples having trouble conceiving experience this as infertility. A major cause, if not the single biggest reason (among several), is leptin resistance.

A major drug company cancelled its synthetic leptin trial (planned for weight loss) because it worked too well

After spending many millions of dollars, and getting well into the FDA approval process, a major US drug company halted its clinical trial of synthetic leptin because releasing the drug would have negated the need for other, more profitable drugs they, and the rest of Big Pharma, sell.

The company arrived at the stunning realization that once you fix a person’s broken leptin system, a plethora of the body’s most vexing problems simply vanish. They realized how influential the leptin system is at controlling biological programming throughout the body, and how adept it is at doing its job. Therefore, if they were to allow synthetic leptin onto the market, they would be teaching the entire healthcare industry what really causes dozens of chronic, degenerative diseases… and why Big Pharma is doing a horrible job at fixing them with their synthetic drugs.

By releasing the cure to so many profit centers… I mean diseases… they would, in effect, be digging their own grave. It simply won’t do. As with all solutions that work too well, have too little markup, or are not patent-protectable, they had to stop it before it threatened their monetization and control over many disease processes.

How to tell when you’re leptin resistant (and test for it)

The easiest way to tell if you are leptin resistant is to look at yourself naked in the mirror. The very presence, or acute absence, of fat mass tells you if your leptin receptors are reading your leptin levels correctly, and responding appropriately. That means you can tell if your leptin reception is broken based on results. Too heavy, or too thin: both mean you’re leptin-resistant. It’s possible for those at a normal weight to be leptin-resistant as well (as other factors bring you into balance).

There are simple, straightforward tests you can do to give your healthcare providers objective measurements to evaluate. However, they’re rarely used by clinicians because leptin resistance is not widely understood or practiced yet. And the tests are not covered by insurance.

Low vitamin D level is a good indicator of leptin resistance to start with. But even better are a “Highly sensitive C-reactive protein” test (hsCRP) and a “Reverse T3” test. Practitioners have long used the common “C-reactive protein test” to measure inflammation. So scoring high on the standard-sensitivity C-reactive protein test reveals that your leptin receptors may be responding poorly to leptin due to C-reactive protein binding to leptin and interfering with its function, and/or a systemic inflammation.

C-reactive protein test is a common measure of inflammation. A Highly Sensitive C-Reactive Protein test (hsCRP) measures low levels of C-reactive protein in the blood.

The other good indicator of leptin resistance is when you score high on a Reverse T3 test. The hormone Reverse T3 suppresses thyroid function because it acts in opposition to the hormones T3 and T4 that run the thyroid. For this reason, leptin resistance and thyroid dysfunction usually go together. You can surmise how leptin-resistant you are by seeing how inappropriate the leptin system’s instructions for the thyroid are (i.e., slowing down the thyroid when the leptin system should be speeding it up).

This also explains why standard thyroid tests can mislead you when you have leptin resistance: Your thyroid probably isn’t broken. That’s the least likely, most severe, condition. Leptin resistance is more likely to be causing slow metabolism issues (along with fluoride decreasing T3 and T4 levels). But leptin dysfunction is making it appear as if your thyroid needs repair (via hormone replacement).

Consequently, anything you do to try to fix your thyroid, such as hormone supplementation, is misguided and potentially counter-productive because thyroid glands are not normally the weakest link: toxicity and inflammation are (from fluoride, blue light, C-reactive protein, and other pro-inflammatories). As a result, supplementation can uncouple your thyroid system from the feedback mechanism that’s supposed to control it, eventually weakening your endogenous production.

Restoring leptin function

DHA. To start with, you can protect your leptin receptors from retinal and inflammation damage by having more DHA (and its electrons) available to neutralize the positive charge resulting from broken vitamin A-to-photoreceptor bonds (the blue light “beat down” we talked about earlier). Eat more seafood with DHA in it, such as oysters and cold-water fish. Liver from grass-fed animals has more DHA than regular beef, lamb, etc. But seafood is still the best.

Cold exposure. Next, you can reduce your leptin level through cold exposure. Cold exposure turns on ancient temperature regulation pathways Nature installed in mammals to help them survive winter weather. As part of this seasonal programming, cold exposure increases production of “uncoupling protein 1,” which stretches out the respiratory proteins on purpose to make the ETC less efficient – meaning more heat.

Brown fat. Cold exposure also activates fat-burning pathways that turn white fat into brown fat. Brown fat’s enviable ability is all of it goes into heat production, rather than ATP. These two mechanisms – uncoupling protein 1 and brown fat usage – turn up the furnace function of your mitochondria, thus dissipating calories as heat, instead of retaining them.

Reducing inflammation everywhere. It’s the side benefits of activating fat-burning pathways that will really blow your mind. Researchers believe leptin evolved from a pro-inflammatory cytokine the body uses widely to promote inflammation, called IL-6 (interleukin-6). As discussed, inflammation is beneficial when it’s acute and temporary. But inflammation becomes destructive when it stays switched on when it’s no longer needed.

The point to ponder deeply here is this: As temperature on the skin goes down, so does inflammation. They’re a coupled system. Our ancient seasonal programming lowers leptin and IL-6 levels, as it burns fat and generates heat. That’s how cold exposure works. So when you’re exposed to the cold, not only do you burn more fat, but it also stomps out a variety of inflammatory conditions such as diabetes, heart disease, and cancer as a consequence of turning down inflammation.

This is why Dr. Jack calls obesity an inflammatory brain condition, and why The Wim Hof Method is renowned for reversing dozens of chronic conditions using cold exposure. The implications are staggering.

Dr. Jack’s Leptin Prescription. Finally, the way to get your leptin sensitivity back is to retrain your brain to see leptin at the appropriate times in the day, and to avoid seeing it at the wrong times of the day. Here’s why: Leptin signaling is supposed to be synced to daily cycles of daylight, darkness, wakefulness and sleep. That’s because fat-burning and the release of growth hormone, for example, work best when they happen on schedule with circadian rhythms.

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the mito man home to the work of Randy D Lee