Bodyweight Regulation: Leptin Part 3

Ok, so now that you know what leptin is and a little bit about what regulates leptin levels, I want to look at what leptin ‘does’ in the body. The short answer is a whole lot of things.

Here’s the long answer:

Like most hormones in the body, leptin has effects nearly everywhere in the body. In skeletal muscle, it’s involved in promoting fat oxidation, it impacts on fat cell metabolism directly, liver metabolism, is involved in immune system function (which may be why dieters get sick when they get very lean) and more recent research is implicating effects on brain function, neurogenesis, breathing and a whole host of other stuff.

Of some interest, leptin levels are crucially involved in both puberty and fertility, it’s been known for decades that a certain level of body fat was required for puberty to hit and achieving critical levels of leptin appears to play a role in allowing puberty to begin.

The handful of folks who don’t produce leptin never hit puberty, for example and it’s thought that some of the reason children may be hitting puberty sooner is because increasing childhood obesity is causing them to hit that critical level sooner.

In a similar vein, leptin is a key factor in regulating fertility, essentially it ‘tells’ the body and brain that it’s well fed enough to spend calories on things like reproduction and making babies. This at least partly explains why dieters are very low levels of body fat lose both sex drive and the ability to function.

Loss of menstrual cycle is a well known effect of dieting and intensive training and while it was always thought to be related to body fat levels per se, it appears that energy availability (which, remember, leptin tells the body about) is a bigger factor. Essentially, when the body ‘senses’ that energy availability is insufficient, it shuts down what are essentially ‘extra activities’ such as reproduction.

In this vein, the most recent ideas about what leptin ‘does’ in the body are that it acts as an adipometer, a measurement of energy stores that tells the brain whether there are sufficient calories available to spend them on things like making bone, maintaining immune function, etc. Essentially the same concept I’m describing here.

My point being that leptin does a lot of stuff in the body, but that’s not mainly what I want to talk about here. Rather, in keeping with the theme of this blog series, I want to talk about leptin’s potential roles in bodyweight/bodyfat regulation.

When it was originally discovered, leptin was originally conceived as an ‘anti-obesity’ hormone, it was thought that leptin should act to prevent weight gain. This led one researcher to quip (and I’m paraphrasing here) that “If leptin is meant to act as an anti-obesity hormone, it has to go down in history as the most ineffective hormone in the human body” or something roughly to that effect.

As I mentioned in previous blog posts, obese individuals invariably have high levels of leptin, raising levels in those folks does little to generate weight loss and because of that failure, everyone sort of moved on in terms of using leptin as a treatment for weight loss.

The problem is that early ideas about leptin were conceptually incorrect; rather than acting as an ‘anti-obesity’ hormone per se, leptin appears to act as more of an ‘anti-starvation’ hormone. That is, leptin doesn’t act to prevent weight gain, it acts to keep you from starving to death.

This reconceptualization would go a long way towards explaining the apparent assymmetry in the bodyweight regulation system I discussed previously: the body doesn’t defend against weight gain very well, it defends tenaciously against weight loss.

Various research found that the drop in leptin was a key aspect triggering (or at least mediating) the effects of starvation (dieting is just starvation on a smaller scale) in humans. In that vein, several studies had individuals diet before replacing leptin to pre-diet levels. This raised metabolic rate, normalized thyroid and increased fat loss. For example.

Basically while trying to raise leptin in overweight individuals is pretty much a bust, preventing leptin from dropping on a diet (or raising it back to normal levels after weight has been lost) is where the real action is.

In this vein, recent work has found that females suffering from amenorrhea (a loss of menstrual cycle) respond to replacement levels of leptin with improvements in reproductive function, bone health, thyroid and overall hormonal axes, etc. Without weight gain.

So now you know basically what leptin ‘does’ in the body at least conceptually: it signals the brain about energy stores (both body fat levels and energy intake) and appears to act primarily as an anti-starvation hormone. Next time I’ll look at mechanistically some of what it does (e.g. impact on appetite, etc) and then about how to go about dealing with this on a diet.

Read Bodyweight Regulation Part 4

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5 thoughts on “Bodyweight Regulation: Leptin Part 3

  1. I started navigating the web a bit about leptin and read that it is not sold OTC anymore. Banned? I found a site that lists a leptin-related product, albeit out of stock, that suggests increased dosage with lower bodyfat while never giving the actual amount of leptin-per-serving. I can see why one would increase or decrease the dosage, but are there any numbers on how much leptin is present during maintenence on healthy individuals, for example? I see in the PubMed abstract that the study dealt with only 10mg per day. I would be interested to see the number on how “badly” leptin crashes during a caloric restriction.

  2. Leptin was never made available OTC or outside of clinical use and an effective daily dose would run between $500-1000 per day.

  3. Interesting!
    As I mentioned before I was very leptin deficient (level <2) after losing 160lbs and maintaining several yeras a bmi of 20.
    Another interesting effect I’ve observed is that I no longer have the scary “apneic” episodes. It used to be that when I was very sleep deprived, I would lose the ability to “breathe”, especially while lying down. I had to consciously try to take breaths. I related this to the fact that after extensive sleep deprivation my already low leptin was below the critical point necessary to maintain respiratory function. Scary, right? The apneic episodes were the worst when I was restricting food and lower in weight.

    Since the replacement I never, ever have apneic episodes even if I am sleep deprived.

    My immune system is heaps better. Used to get mild cold and flu symptoms whenever I was sleep deprived (due to the higher cortisol, and lower leptin, I suppose). Now I never get cold and flu symptoms even if sleep deprived.

    I also had a tumor on my pinky that literally ate itself up. Amazing!

    I

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