stephan announced on his blog that he will release his idea on "a method that goes beyond symptomatic treatment and allows the body to naturally return to a lower fat mass". being that he has written extensively about leptin in the past, i'm sure that leptin sensitivity and set point theory will factor in it to some degree. i also just finished reading the amazing back and forth between dr rosedale and dr k on a recent paleohacks post. there seems to be momentum towards the idea of leptin sensitivity and set point theory making it's way into mainstream consciousness much the way the ideas of insulin resistance and metabolic syndrome has in the last ten years. i'm not a science-oriented guy so i'm left wondering where does it fit in with what we've been learning and applying based on our theories on insulin resistance for the last ten years? does leptin regulation trump insulin regulation or is it a totally different pathway(if that's the right terminology)?
The merit worthy "grand theory" of obesity and health will unlikely be new, but will likely be connected with insulin, leptin and leptin resistance. The point missed by most everybody concerning leptin resistance is that leptin levels and leptin resistance is not primarily determined by how much fat you have, but how much fat you have is determined by leptin and leptin resistance. Leptin levels and therefore leptin resistance is determined more by acute nutrient related spikes in serum leptin levels similar to what happens with insulin. I have maintained for decades that the primary (though not only) cause of insulin resistance is due to insulin spikes secondary to glucose spikes, primarily from high non-fiber carbohydrate meals. This constant high exposure of cells to insulin causes varying degrees of insulin resistance depending on the cell type, similar to being in a room with a powerful odor where one's ability to smell that odor diminishes over time. I believe the same happens with leptin, whereby repeatedly high spikes in leptin in response to particular nutrients including sugars (including those from non-fiber carbohydrates) and certain amino acids, result in leptin resistance. The leptin resistance then diminishes the body's attempt to tell the brain how much fat is stored i.e. how fat it is, thereby impairing leptin's ability to properly regulate fat storage, not just how much, but also where it is stored, being then overly stored in visceral tissues. I talked about this many years ago, a good example being the following; http://articles.mercola.com/sites/articles/archive/2004/12/01/leptin1.aspx
As far as the relationship between insulin and leptin, I will quote myself from that article of seven years ago; “Metabolism can roughly be defined as the chemistry that turns food into life, and therefore insulin and leptin are critical to health and disease. Insulin works mostly at the individual cell level, telling the vast majority of cells whether to burn or store fat or sugar and whether to utilize that energy for maintenance and repair or reproduction.
Leptin, on the other hand, controls the energy storage and utilization of the entire republic of cells allowing the body to communicate with the brain about how much energy (fat) the republic has stored, and whether it needs more, or should burn some off, and whether it is an advantageous time nutritionally-speaking for the republic to reproduce or not."
Insulin is evolutionarily older and harks from a time when glucose was a primary fuel in single-celled organisms prior to oxygen inhabiting much of the atmosphere. That took plant life to inhabit the earth. Fatty acid oxidation requires oxygen and thus it had to wait for oxygen to be available. However in humans, fat is meant to be our primary fuel, with glucose available as an emergency anaerobic backup, i.e. for severe and emergency situations, such as running from a sabertooth tiger (that we have carried into the future as stress-related work situations where the elevated sugar is not burned causing continued adverse effects on glycation, insulin resistance, leptin resistance etc.)
Now, however, oxygen is readily available and now fat ought to be the primary fuel burned. The fact that it is not, and glucose is in most people, is, in my opinion, the primary cause of the chronic diseases of aging and accelerated aging itself. The control of fat metabolism is paramount, and the primary hormone that controls this is leptin.
Even in those physiologic situations in humans where insulin is thought to be most important, such as glucose "regulation", leptin may even supersede insulin. New studies are showing that even small amounts of leptin infused centrally, through centrally mediated processes, can greatly alleviate, if not eliminate hyperglycemia in non-insulin producing animals. It apparently controls, to a great extent, gluconeogenesis in the liver perhaps centrally through the vagus nerve, and also by powerfully affecting the SNS. Rather than infusing leptin into the brain, however, we can increase leptin's sensitivity in the brain, to accomplish many of the same benefits on glucose and fat metabolism and therefore obesity, aging, and its chronic symptoms. The way to do this, I firmly believe, is rather than keep leptin high that many others are espousing, it is paradoxically much better to keep leptin low, just as low serum insulin in a non-type 1 diabetic indicates better insulin sensitivity and health, and high insulin indicates insulin resistance and frequently T2 diabetes. Lower leptin is also a nearly universal finding in caloric restricted animals, with many believing that this is partly responsible for the reduced aging phenotype and its benefits.
To keep leptin levels low, and to prevent the chronic spikes in leptin that I believe are responsible primarily for leptin resistance, one must avoid those foods that cause these spikes. These foods are sugars, including those from starches, and the metabolism of particular amino acids from excess protein. Oddly enough, the macronutrient that least affects spikes in leptin are fats. I have written much over the years on this subject and a simple Google search under my name should find some of these.
Yes, it appears leptin regulation trumps insulin regulation, but if we don't know what causes leptin resistance then it's not really very helpful to know this. I'll attempt to explain what I mean.
If (barring massive and conscious overeating) we are obese if and only if we are leptin resistant, then our being leptin resistant doesn't tell us anything helpful. All we have done in that case is to rename obesity. It would be like this: "Why am I obese when I never gain weight and never lose weight?" "Well, you have leptin resistance." "What's leptin?" "It's a messenger hormone that operates on a negative feedback loop. The more fat mass you have, the more leptin you produce, which is a signal to your body to eat less. But if you have leptin resistance then you're producing plenty of leptin, but your brain is resistant to its effects, so you keep eating." "OK, so you're telling me that I'm obese because my brain doesn't recognize the hormone that tells me not to be obese." "Yes." "So how is that helpful?"
And if the response is instead: "well, there are methods that are shown to decrease leptin resistance," then my response would be: good, but if there's no obesity without leptin resistance, then you're just telling me, effectively: "there are methods that are shown to decrease the fat mass setpoint." In which case ... Please do tell me about them!
If (notice I said "if" from the very beginning) it is correct that we are obese if and only if we are leptin resistant, then it is obviously a good thing to be aware of that fact, especially if you're an obesity researcher; you can look at the various things in the body that interact with leptin, etc. So it will help get you on the right track. But if what we laypeople are interested in is what we should eat and how we should exercise to stay thin -- that is, what we can actually do about it -- then I don't see how knowing about leptin helps us.
We have our suspicions about what causes obesity. One possibility is fructose. Lots of evidence for that; might do something to the liver, etc., etc. Another possibility is fructose + high PUFA. This one seems to work well with lab mice; in fact if you need to get your mice fat that's a pretty reliable way to do it.
Maybe when Stephan comes out with his grand theory (and I am pretty excited) he'll be able to account for all of the different causes of obesity (and, along with them, the different causes of weight loss). I would bet that the last few phrases of the theory will be: ".... which causes leptin resistance, which means the brain isn't getting the message that it has body fat to burn, which means a high body-fat setpoint is retained." That will be the last part of the theory -- but it's what comes before it that interests me.
Acupuncture is not pseudoscience. People's interpretation can be flawed but acupuncture is a physical therapy sometimes it works and sometimes it doesn't. No different than another modality.
It does not have to be an either/or. Everything in your body has some modest amount of coordination. Insulin and leptin could have a strong physiological link.
(Not to use the above to endorse any pseudoscience craziness like acupuncture, just speaking to areas where a physical connection can be made).
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