As for leptin itself, I've heard that it has a long term function, that it offers the body a long term signal about energy rather than a short term one. So it's not that immediately when your fuel reserves hit the red zone the signal goes off but that after a while it goes off because the reduced energy state has been around for a while. Hence the reason it's hard to go from obese to not obese and stay that way without a struggle.
Female, 5'3", 49, Starting weight: 163lbs. Current weight: 135 (more or less).
Starting squat: 45lbs. Current squat: 170 x 3. Current Deadlift: 220 x 3
Perhaps you skimmed my original post a bit quickly and missed the part where I indicated that I was about to make an argument from analogy? Or maybe your understanding of "analogy" differs fundamentally from mine? In any event, when I intend to make an argument from biochemistry, I will label it as such in order to help you and others identify it. That was my intent for part 2 of this, but if I need to accelerate my schedule and address some things now, then so be it. Thank you for your search tips, by the way. It may surprise you to learn that I'm actually quite proficient with Google Scholar. As proof of this, you may look at my posts on intermittent fasting, or check out my post on leptin on my blog. Be warned, however, that it is substantially longer than my original post.
I don't know how this abstract that you pulled supports your argument, such as it is, so I've gone and highlighted some salient bits that actually support mine.I just pulled this from Google Scholar for instance.
The hormone leptin, secreted predominantly from adipose tissue, plays a crucial role in the regulation of numerous neuroendocrine functions, from energy homeostasis to reproduction. Genetic deficiency as a consequence of leptin or leptin receptor mutations, although rare in humans, leads to early onset of chronic hyperphagia and massive obesity. In most human obesity, however, leptin levels are chronically elevated. Under these conditions of persistent hyperleptinaemia, leptin resistance develops, and signalling through the leptin receptor is curtailed, fuelling further weight gain. Here, we review the role of leptin receptors in the regulation of feeding and obesity development. Leptin receptors are found in each of the major components of the CNS “feeding” circuitry—the brainstem, hypothalamus and distributed reward centres. Through these receptors, leptin exerts influences on signalling and integration within these circuits to alter feeding behaviours. Although some progress is now being made with peptide analogues, the leptin receptor has not proved to be amenable to small molecule pharmacological intervention to date. Where clinical benefit from recombinant leptin administration has been achieved, this has been under circumstances of complete endogenous leptin deficiency or relative hypoleptinaemia such as in lipodystrophy.
Keywords Leptin – Leptin receptors – Obesity
First, there are two types of leptin genetic mutations, one in the leptin that you produce, the other in the leptin receptor that is expressed in the hypothalamus ( I limit myself to the hypothalamic receptor, b/c that's the one responsible for affecting metabolism and appetite ).
Ob/Ob Mouse Model : Defective Leptin
The Ob/Ob mouse has a recessive mutation in the gene that encodes for the leptin peptide that results in a base pair substitution that truncates the leptin molecule. This renders it incapable of binding to and activating the leptin receptor in the hypothalamus. This type of leptin deficiency can be addressed by injecting recombinant leptin into the organism, much in the same way that insulin is injected to compensate for the malfunctioning pancreatic beta cells.
Db/Db Mouse Model : Defective Leptin Receptor
This recessive mutation results in a malformed receptor in the hypothalamus which means that effectively, despite producing copious amounts of leptin, the brain is blind to leptin. This condition cannot be addressed by administration of exogenous leptin, rather, you need to somehow reengineer the receptors in the brain, which is rather more difficult than producing recombinant leptin. This is what "the leptin receptor has not proved to be amenable to small molecule pharmacological intervention to date" means.
Once you get beyond the background information and the theorizing of the abstract, you are left with the facts as those researchers know them:
- In a few unlucky humans with a genetic mutation, leptin driven morbid obesity starts from an early age. It doesn't sneak up on you in middle age.
- If you happen to have the human version of the Db/Db mutation, there is nothing they can do for you, short of growing you a new hypothalamus
- The only clinical successes that exist are in those cases where the subjects don't produce leptin, but were injected with exogenous leptin
Note that these facts say absolutely nothing about the development of "late onset leptin resistance", probably because there is no such thing. The researchers assume / theorize that the role of leptin is to decrease appetite and increase metabolic rate. This assumption does not jibe with the observation that you can have high circulating leptin levels and normal appetite and metabolic rate. This then forces them to start inventing explanations for the data, and that's the genesis of the leptin resistance hypothesis.
I question the base assumption that the role of leptin is to stimulate metabolism and curb appetite. I do not question the existence of leptin, nor the biochemical pathways of its action. I do not need to do so. I leave that intact. What I do say, is that if we reverse the direction of the base assumption, that the role of leptin signalling is not to make us thin ( which is pure wishful thinking, by the way ) but rather to make us fat. Fat enough to survive periods of uncertain food availability. With this assumption, all known data about leptin makes sense. I do not need to invent a new hypothesis to explain the data away. I can explain why Ob/Ob and Db/Db mice and humans exhibit the behaviour and phenotype that they do. Moreover, I can also easily explain normal mice and humans with high circulating leptin levels with the exact same framework. If you subscribe to Occam's Razor, that in itself is enough to select my assumed role for leptin in fat metabolism.
Last edited by pklopp; 03-21-2012 at 01:22 PM.
Google Scholar still needs to time to mature as an "academic" resource, IMO.
I found I couldn't do 50g of protein for breakfast without trimming fat. It was just too darned much food for me to eat. Eggs and some relatively lean meat could get me there. As it is, I seem happy with more like 30-35g of protein at breakfast and a bit of fat. It keeps me going for a good 5-7 hours until lunch.
The no-snacking idea seems pretty solid to me. It makes sense to let your insulin levels subside after eating. It also matches the way our ancestors ate, too. Does that mean it has anything to do with changing the way my leptin receptors work? I have no idea.
SW175ish GW140 CW157
Official for real start date 1/10/12
Ok so here is my take on it- the leptin reset is similar in some ways to the Zone diet albeit with fewer carbs. My experience of the Zone over many years was that yes, eating the animal based protein based breakfast did shut off my hunger and did allow me to eat less, but as time this became a system of diminishing returns as I probably developed low leptin and at one pt may have veered in a little bit of anorexia- ie, chronic undereating.
From what I've read grains like wheat contain lectins that damage leptin signalling so that even if you eat less ??-- you may or may not be able to, it really becomes more a willpower thing- your brain will not read that you have been nourished/fed and will keep you fat. So it really isn't that wheat is any higher in calories.
I've wondered since wandering on to this forum if I need to go back to breakfast to "reset my leptin" but I already did that a decade and yes it helps but.............. just eating primally, no matter what time of day, seems to be what makes the difference for me. I've found eliminating carbs a few days a week (while it is still cold out- I agree with Dr. Kruse about that totally) has helped a lot. I woke up today refreshed at 6 without an alarm
Going back to the Zone, Barry Sears says that avoiding "carb hell" helps balance *eicosanoids*- this is the reason for being able to wake up refreshed.
Honestly just not so sure how worthwhile the leptin theory is apart from don't eat wheat and grains and don't eat carbs, eat primally, you will not be as hungry and automatically eat less, but also buy yourself some extra nutritious calories in case you want to eat more, which on occasion you might.
He's totally right about the high protein breakfast, IMO, but 30g is enough for me.
F 5 ft 3. HW: 196 lbs. Primal SW (May 2011): 182 lbs (42% BF)... W June '12: 160 lbs (29% BF) (UK size 12, US size 8). GW: ~24% BF - have ditched the scales til I fit into a pair of UK size 10 bootcut jeans. Currently aligning towards 'The Perfect Health Diet' having swapped some fat for potatoes.