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Thread: Leptin: It probably doesn't do what you think it does.

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    Nov 2010

    Leptin: It probably doesn't do what you think it does.

    Those of you that recall my posts on intermittent fasting know what you are in for with this, but for those of you that don't : it is going to be long, probably multi-part, but hopefully worth your time.

    What This Post Is Not

    I am not going to directly address the myriad of posts that appear in the forum regarding the successes that people have had following a "leptin reset" diet. I am sure that all of you that have posted to this effect are sincere, and further, I am glad that you have experienced success in your quest for a better you. My purpose is to determine, to the extent that I can, whether these successes can be at all attributed to the action of leptin, or to some other fundamental factor.

    Argument from Analogy

    Leptin is interesting to both scientists and lay people because it is secreted exclusively by adipose tissue in direct proportion to adipose fat mass. Further, leptin has profound effects in the brain, not the least of which is that in those individuals that lack functioning leptin or leptin receptors, the result is a voracious appetite, lowered metabolic rate, and an attendant acretion of adipose fat mass. Administering recombinant leptin in cases of leptin deficiency results in a decrease in appetite, increased metabolic rate, and weightloss. This has led many to conceive of leptin as the fuel gauge of the body, conveying long term energy status information to the brain, which will then modify metabolism accordingly.

    Most of us in have at least a passing familiarity with cars which brings with it a pretty good understanding of how a fuel gauge works. If we're speaking of a late model car, then the fuel monitoring system consists of a sensor located in the gas tank, a gauge in the dashboard to indicate fuel levels to the driver, and most often, a warning light that illuminates when fuel levels drop dangerously low and serves to draw the drivers attention to that fact so appropriate action can be taken. Using this as the base analogy for how the leptin feedback system works in metabolism actually turns out to be quite useful.

    Consider those occasions when you were driving and the fuel warning light illuminated. I am quite confident in asserting that your normal behaviour changed, and you immediately started looking for the nearest gas station. This situation, analogous to metabolically low circulating leptin levels, resulted in an increase in your awareness / appetite for gasoline. Further, your gasoline consumption rate ( metabolic rate ) was lowered as you presumably didn't accelerate as vigorously as you otherwise might, you began coasting rather than applying the brakes, and maybe even tried timing lights to avoid having to stop and then accelerate from a standstill. Once you fed your car with gasoline, you reverted to your normal driving habits.

    And this is where all the problems begin, because if you were to believe leptin researchers and proponents of the leptin insensitivity theory, then you would not predict that normal driving behaviour would resume. Rather, you would predict that the more fuel there was in your fuel tank, the more profligate you would be in its use. That is, putting it in conventional metabolic terms, as leptin levels increase, metabolic rate should increase, and appetite should decrease. If this does not occur, conventional leptin wisdom has it that what is being observed is leptin insensitivity. But if we were to put this back into automotive fuel gauge analogue terms, it becomes a ludicrous proposition. Except in rare marginal cases, nobody sets out to purposely waste gas from a full tank. Instead, normal people without personality disorders stop thinking about it, and commence going about their regular business because they are concerned with having a qualitative amount of gas in their tank, they merely want "enough". The idiot light in the dashboard is a last ditch effort short of your engine dying to draw your attention to the fact that you definitely do not have enough fuel.

    The Metabolic Idiot Light

    So what if leptin is the body's equivalent of the idiot light? If this were the case, then we would definitely expect to see an asymmetric response to leptin levels, with low leptin levels eliciting much stronger responses than high levels. If you were on the verge of starvation with death imminent, drastic measures would be called for. Conversely, if you're sporting a nice fat pad around your midriff, there is really no cause for metabolic concern.

    We see this play out with the seminal research on Ob/Ob mice that produce malformed leptin incapable of binding and activating the hypothalamic receptor. These mice are in constant panic mode, exhibiting voracious appetites despite extreme adiposity - the idiot light does not turn off regardless of how much they eat. Infusing normal leptin into their system turns the idiot light off, the fuel gauge registers a full tank, and they resume driving as normal, eating less and increasing their metabolic rate - reverting to normal. Note that this interpretation of low leptin as the metabolic idiot light fits the observed data, and, moreover, does not suffer from the problem of leptin insensitivity because what is of concern is low leptin, not having "enough".

    What Does This All Mean

    Practically speaking, if this framing of leptin as idiot light is accurate, then there can be no such thing as a leptin reset diet intended to increase leptin sensitivity, because your body is already quite sensitive to leptin levels, it's just that it only cares about low levels. You may, however, find that leptin starts to play a role when you successfully lose weight, to the extent that you come close to the threshold of what in your metabolic context constitutes "low" leptin levels, at which point, your appetite will kick in, and your metabolic rate would drop. However, this would happen irrespective of the particular details of your diet, whether you're on a juice fast or overdosing on protein, it doesn't matter. Once you cross the low leptin threshold for you, appetite and metabolic rate will be affected.

    There is a certain liberation that comes from seeing things in this light, because it frees you from obsessing about controlling your leptin levels, and focuses your attention back on your diet. Which then brings us full circle to the question of what should you eat? Paleo / primal is probably not a bad place to start.

    Last edited by pklopp; 03-27-2012 at 05:40 PM.
    My blog :

    Interested in Intermittent Fasting? This might help: part 1, part 2, part 3.

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