Series: Leptin

Rewiring The Leptin Rx Reset

Evolutionary strategy is based upon finding an environmental niche and exploiting it. Evolution is based upon change and the natural adaptations to it. Today, we are going to explore how some environmental triggers might open a “biochemical trap door” that will allow me to add a new recommendation for you to consider adding to the Leptin Rx reset protocol for those who are LR. I am beginning a series on circadian biology to show you how this all ties in together. Today, I will give you a very cursory review of why circadian biology, leptin, and environment are critical to using the Quilt to obtain your Optimal life. Why is circadian biology critical to humans? For evolution to work Optimally, a cell first must adapt to its environment. The first situation any living cell would be subjected to in an earth day is a period of day and night. Over time it would also be subject to the seasons in our environment because of the earth’s revolution, tilt, and angulations of the sun. As time continued on, further life would have been subjected to solar variations and would have had to account for it. It also has to find food to make energy (ATP) to survive, and it also has to control its own cellular division. The epic battle for the cell is to have the regularly expected circadian cycles found in our environment and ”yoke” those signals to its metabolic cycle and to its growth cycle. Most people know that the suprachiasmatic nucleus (SCN) in the brain is where the circadian pacemaker lies in humans. It monitors this dance between darkness and light, and the seasonal cold and hot temperatures in our environment to help control and monitor our own growth and development. Evolution apparently agreed to use these signals in all living things because this is what it uses for all life on earth today. What most people do not know is how leptin plays a massive role in regulating it. Many people and physicians think it plays a small role. Recent research has revealed that leptin can induce expression of a neuropeptide called vasoactive intestinal peptide (VIP) through the VIP cytokine response element. This is an epigenetic modification from our environment directly signaling the master hormone in our body. So what does VIP actually do?

So You Completed The Leptin Rx? What’s Next?

Once you have added the Leptin Rx to your paleo/primal template and you have successfully experienced all the "small wins" that I mentioned in the Leptin FAQ's blog, what should you do next? If you recall reading the blog on how the leptin Rx works, it basically is a plan to make your gastrointestinal tract perform visceral exercises that it is not accustomed to performing, in order to cause neuroplastic changes in your hypothalamus' arcuate nucleus. It uses the vagus nerve as the "stimulator" to send these new messages to the brain. After a period of time, the inflammation will slowly dissipate at the median eminence, and these afferent signals will force expression of certain genes that have been repressed since we were in utero. These genes and pathways are hardwired into our DNA at conception, and used until the child is 12-24 months old. After this time, they are not expressed any longer, because transgenerational epigenetics favors instead the use of the leptin receptor from an evolutionary perspective. This occurs because the leptin receptor in the arcuate nucleus is far more sensitive and accurate in accounting for electrons from food than was using older circadian and ultradian cycles that we used in uteri during morphogenesis. The human brain learns "what neural circuits" to use by repetitive firing. We have a saying in brain surgery, nerves that fire together wire together. This is the basis of the theory of Hebbian learning. These exercises I told you about in the Leptin Rx signal hypothalamic neurons to adapt to these visceral responses to food in a new way, to sensitize the leptin receptor in order to account for electrons from food in precisely how it was designed to do by evolution. In essence, we are altering the genetic expression of the genes in our arcuate nucleus. I describe it to my patients as "performing brain surgery on them without using a blade." The visceral responses to the Leptin Rx are transcribed by the vagus nerve, and this information is sent to the brain. This message is dramatically different than the one the patient is used to giving the leptin receptor, and the new message induces changes to the neuropeptides in the brainstem. After some time, (6-8 weeks for most) changes will be induced. These can be followed by the clinician or the patient. Those clinical signs are outlined in the Leptin FAQ blog post. In doing this, we force the neurons to see neurochemical signals that radically confuse the leptin receptor and the brain. The brain's response to a signal it does not understand is to revert to an older known pathway or to learn a new way to tackle on old problem. I would suggest you watch How your brain re-learns from 2007 by Dr. VS Ramachandran in a TED talk. He exquisitely explains how this type of learning is stimulated in the brain for phantom limb pain and its treatment. One need not use expensive technology to induce gene expression. It is possible to do without an NIH grant too. It requires some synthesis of thought and experience. When you understand the essence of how the brain works, you just need to design a program and force it upon the brain to decipher what to do. That is the essence of the Leptin Rx reset.

How Does The Leptin Rx Work?

Many people have contacted me about "why" the leptin Rx works and "how" does it work. Many people in the blogosphere have made some claims that much of what is in the leptin Rx is a rehash of the work found in some diet books. Well, today's post is being done to show you the science underneath my recommendations were formulated and made. None of the underlying science I will mention to you about neuroplasticity will be found in any diet book mentioned in any blog post that I know of. Most of you know I am a neurosurgeon, and as such, I was dramatically influenced by two world famous neurosurgeons named Wilder Penfield and David Kline. Dr. Penfield was the first neurosurgeon to use electrodes on the brain to map it prior to surgeries to avoid neurologic damage during tumor removal. Dr. Kline was and still is the pre eminent world expert in peripheral nerve surgery. I happened to train with Dr. Kline in New Orleans, and got turned on to his work, Dr. Penfield's work and the work of Dr. Merzenich in the early 1990's before leptin was even discovered. Dr. Michael Merzenich work on sectioning the median nerve in the hand and seeing how the brain remapped its sensory territory in the cortex via micro-electrodes was brought to my attention by Dr. Kline while I was a resident.

The Leptin Rx: FAQs

What should I do before I start The Leptin Reset? Before you start, take a picture of yourself from all angles. Don't be bashful or you'll be sorry in 18-24 months. Next, weigh yourself naked. Let your significant other or a family member take this picture. Go to the store and buy a piece of clothing that does not fit you now, but will when you have met your goal. Remember, calories are important when you're LR (leptin resistant) and mean nothing once you are LS (leptin sensitive). Macronutirents count when you're LR and mean nothing when you're LS. How do I determine if I am leptin resistant? Remember, you can be LR (leptin resistant) if you're fat or skinny. If you're overweight by more than 30lbs, it is a lock you have some degree of LR. If you're underweight by 20 lbs, you are likely LR, too. If you had an eating disorder, you're likely suffering from a serious leptin issue. The easiest test is to look in the mirror. The mirror does not lie and it is really cheap. For those people who still can't be sure after peeking in the mirror, you can order some blood tests. My favorite is the HS CRP (highly sensitive C-Reactive protein) and the reverse T3 tests (but there are others). They are accurate in over 90{a7b724a0454d92c70890dedf5ec22a026af4df067c7b55aa6009b4d34d5da3c6} of cases.

Central Leptin Dominance: Part 3 – King of The Hill

So now that we examined Dr. Lustig's insulin theory of metabolic control we need to take a look at the reward tracts that are located in the human brain. These tracts have been well studied and their neurochemistry is well understood. What appears not to be as well known is how the hypocretin neurons and the leptin receptor control and modulate their activity. The key point here is that the dopaminegic tracts eloquently spoken of Dr. Guyenet's reward series are the "efferent only" path that is part of the effector arm of the leptin receptor and the hypocretin neurons. This means, in English, they are playing second fiddle to the leptin receptors and are not the dominant cause of obesity. They clearly play a major role in the neuro-circutry but they do not control obesity. They carry out the action but the orders were given by someone else. One of the reasons I had a major problem with the reward series, is because of my "day job" as a neurosurgeon. I have had the opportunity to operate on many brain tumors in the reward tracts and never have I ever seen either preoperatively or postoperatively one patient develop severe morbid obesity. If these tracts were truly dominant causes this would lead neurosurgeon and neurologists to see many patients with this problem. Well, we do not. That was a big issue for me with the theory. The second issue I had with it was that when we neurosurgeon's have patients with brain tumors involving the hypothalamus we see tremendous effects on feeding, obesity and on anorexia. This is well documented and I have personally seen this in many cases. Dr. Lustig pointed this out in his AHS 2011 talk when he showed some clinical cases of craniopharyngioma's and of hypothalamic trauma's that resulted in morbid obesity.

Central Leptin Dominance: Part 2

Continuing on in the Central leptin series we will resume in Orlando, Florida. In Orlando, Dr. Myers, went on to say, "In addition to examining the molecular details and importance of specific LRb signals, we are dissecting the regulation and function of individual populations of LRb-expressing neurons and examining the role of leptin in the development of neural circuits. By understanding the totality of leptin action in this way we hope to decipher the mechanisms by which leptin regulates the predisposition to diabetes and other aspects of the metabolic syndrome." This statement carries huge implications. He has found that not only is leptin neurons somatotopically organized in the brain, but the leptin receptor also appears to be somatotopically organized into certain regions that wire and select certain neurons in the brain that modulate all parts of the obesity physiologic response. It also appears that this organization is different in men and women at the parvo-cellular nucleus in the hypothalamus. Certain parts of the receptor control total body glycemic control, others body weight and size, and others power the para-mammillary neurons to directly control fecundity, placental growth and oocyte maturation. The receptor even codes for gender differences! Men and women really are from Mars and Venus when it comes to obesity and fat deposition, and this explains why the endocrine response is different in men and women. We have known men and women have different leptin levels as adults but did not know how or why this happens. Now we do. We now are beginning to understand why it is the case as well. It helps explain why we see can see PCOS and stubborn weight gain together and why fat is distributed differently in both sexes.

Central Leptin Dominance For Health: Part 1

Today, we are going to cut deeper into the leptin story. We need to look at the leptin receptor because its biology will explain why studying macronutients at a dietary level just becomes a confusing mess with seemingly multiple paradoxes. I recently commented on this in Paul Jaminet's blog on August 24th 2011. The comment was very detailed but not written well so I am going to lay out the reasoning in the next few blogs. As most of you know leptin is the lynchpin in my Quilt and sits at position two. Many people might not realize how important it is for health, in sickness, and for optimal endocrine function. It is the dominant factor in obesity and this series is out to show you why this is the case based upon the data coming out of some labs who specialize in this neurobiology. This series is going to be laser like biochemistry on a 30 foot level. When we talk about this type of lab science it is very easy to lose perspective of the larger story I am trying to unveil to you. I have previously called leptin the master hormone of the brain. Remember that the brain has two ways to control things, one is direct neural wiring and the second is the control over the hormonal secretions body wide. Given these two factors, I think I may have under called it, honestly. This hormone signals the entire body's nutritional status, metabolic status, and endocrine status to the brain at all times. The brain in turn uses leptin to regulate total glycemic control, energy balance, and all neuroendocrine function in all systems in humans. This means that energy regulation is centrally controlled by our neuroendocrine system. The brain uses this hormone as an afferent and efferent signaling hormone to know precisely what is going on in our 20 trillion cells body wide. The brain does not have direct wiring to all 20 million cells because of space limitations of our cranium and our mother's vaginas. So it uses hormones and cytokines to extend its power and reach to send signals to those 20 trillion cells.

Where Autoimmunity, Cancer and Disease Collide

READERS SUMMARY: 1. What ties Levee 5, 6, and 16 all together in the QUILT? 2. Why is Vitamin D and Selenium the key to the gut? 3. How does Vitamin K play a role? 4. Why is autoimmune disease, cancer and neolithic disease more common today than ever before? 5. Is there another environmental [...]

Can’t Remember? Is Your Protein Bent?

READERS SUMMARY: 1. Alzheimer's disease is due to lack of electrons which causes compliant design changes in protein phosphatase! 2. Why are the incidence and prevalence growing for AD? 3. What is a proteopathy? 4. Why is protein folding so critical to so many diseases? 5. What kind of nutrition guidelines do I follow to [...]

My Leptin Prescription

I have been asked by many to put a short post out about how I reverse Leptin resistance in my own clinic for my patients. After reading all of the comments left here, at MDA, and on Jimmy Moore's forum, I decided that it was a good idea. 1. First make sure you really are Leptin resistant (LR) to begin with. The easiest way to do this if you are heavy is to look in the mirror. If you're overweight you definitely are Leptin resistant. If you still have a large appetite and crave carbohydrates, especially at night, these are also signs that you are likely Leptin resistant. If you are fit or in decent shape and not sure based upon the above symptoms, I would tell you to go get a blood test and check your reverse T3. It will be elevated. I also recommend simultaneously checking a salivary cortisol level. With LR, you will always see higher cortisol levels later in the day. 2. To regain Leptin Sensitivity (LS) follow a strict Epi-Paleolithic diet. To see an outline of a strict Epi-Paleolithic diet, read Brain Gut 6: Epi-Paleo Rx. The type of fuel you eat is important initially in eliminating the foods that cause Leptin receptors to become nonfunctional.

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