Now, I want you to think back to the first couple of chapters of this book, where I talked about the evolutionary reasons it's so hard to get extremely lean. To your body, becoming too lean is a very real threat to your survival. From a physiological standpoint, that means that your body needs a way to "know" how much energy you have stored.
As you may have guessed, or known from my last book, leptin is one of the primary signals (along with many others including ghrelin, insulin, peptide YY and other as of yet undiscovered compounds) that signals the brain about how much energy you have stored and how much you're eating.
All of these hormones send an integrated signal to a part of the brain called the hypothalamus that "tell" it what's going on elsewhere in your body. Changes in levels of these hormones causes other changes in various neurochemicals such as neuropeptide-Y (NPY), corticotrophin releasing hormone (CRH), pro-opiomelanocortin (POMC) and several others to occur. These neurochemicals regulate metabolic rate, hunger and appetite, hormones and a host of other processes.
So when you restrict calories, causing changes in all of the hormones and neurochemicals mentioned above, and a number of physiological processes change, mostly for the worse. Levels of thyroid stimulating hormone, leutinizing hormone and follicle stimulating hormone (TSH, LH and FSH respectively) go down. This results in lowered levels of thyroid and testosterone. Levels of growth hormone releasing hormone (GHRH) go down meaning GH output can be impaired.
Sympathetic nervous system activity goes down which, along with the drop in thyroid, has a huge impact on metabolic rate. Cortisol levels go up as does hunger and appetite. You get the idea. What you end up seeing is an all purposes systems crash when you try to take bodyfat to low levels. I should note that these processes are occurring to one degree or another during all diets, they simply become more pronounced at the extreme low levels of bodyfat.
Ideally, the opposite effects should occur when you raise calories. However, for reasons I detailed in my last book, the system is asymmetrical: falling leptin (and changes in all of the other hormones) has a much larger impact on the body's metabolism than raising leptin does (unless you're raising it back to normal). So the body ends up fighting weight loss to a far greater degree than weight gain. Generally speaking, people find that it a lot easier to get fat than to get lean. Of course, there are exceptions, folks who seem to resist obesity (or weight gain altogether). Research will probably find that they are extremely sensitive to the effects of leptin (and other hormones), so when calories go up, they simply burn off the excess calories without getting fat.
Most of us aren't that lucky. Rather, like insulin sensitivity discussed above, researchers will probably find that leptin sensitivity is a huge factor influencing how changes in caloric intake affect metabolism. Someone with good leptin sensitivity will tend to stay naturally lean and have an easy time dieting; folks with worse leptin sensitivity (leptin resistance) won't.
You might be thinking that the quick and dirty solution would be leptin injections. As I pointed out in my last book, injectable leptin is a pipe-dream at this point, an effective dose costing nearly $1000/day (not to mention requiring twice daily injections). Using bromocriptine or other dopamine agonists seem to fix at least part of the problem by sending a false signal to the brain by making it think leptin levels are normal.
Recent studies that have given injectable leptin to dieters show that the fall in leptin is one of the primary signals in initiating the adaptation to dieting. However, unlike in rats, injecting leptin into humans doesn't fix all of the problems.
This is because, in humans, there is more of an integrated response to both over and underfeeding. To understand this better, I want to take a snapshot of what happens when you either reduce or increase calories.
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