Posted on

Bodyweight Regulation: Leptin Part 4

Sharing is Caring

Don’t worry, slowly, I’m getting to the point.

So when you are in an energy deficit and/or losing body fat, leptin levels drop.

Although I haven’t talked much about the role of exercise here I’d only note that whether or not the deficit comes from caloric restriction or exercise per se doesn’t appear to have much of an effect on how much leptin drops.

Basically, the body appears to be sensing ‘energy availability’ (defined as energy intake minus expenditure) and adjusting things based on that. I’d, of course, note that exercise still plays plenty of other crucial roles (including psychological, which I am getting back to slowly but surely) in terms of dieting and fat loss.

In any case, what happens now?

Well, a bunch of stuff. Leptin interacts with various part of the brain but the hypothalamus (where the setpoint is primarily thought to be regulated) appears to be the key aspect. In conjunction with the other hormones I haven’t talked much about yet, when leptin drops a bunch of other neurochemicals change. These all have complicated names like Neuropeptide Y (NPY), Agouti Related Peptide (AgRP), Pro-opiomelanocortin (POMC) and Cocaine Activated Receptor Transcript (CART). The names are not that important practically. When these hormones change, they cause other changes further downstream that affect all aspects of metabolism.

There are other regulators as well, in my little Bromocriptine booklet, I pointed out that brain dopamine levels go down when leptin goes down and this appears to play a role in the overall metabolic adaptation to dieting. The whole idea in that booklet was to use a dopamine agonist to ‘trick’ the brain into thinking it was fed, it worked for about half of the people who tried it; I’m still trying to determine what the cause of the variance was.

Lowered dopamine has a secondary effect that low leptin makes animals (mice and rats at least) more likely to addict to drugs when you starve them (there are other mechanisms at work here, of course): they need something to drive the dopamine/reward system. There is also evidence that obese individuals have impaired dopamine signalling in the brain.

In any case, POMC/AGRP/NPY/CART have further downstream effects and regulate things like metabolic rate (which drops when you diet), appetite/hunger (which go up when you diet), activity levels (you tend to get lethargic, burning less calories in daily activity), hormone levels (including thyroid via TRH/TSH and reproductive hormones via LH/FSH), etc. Testosterone and thyroid generally go down as does nervous system output, cortisol goes up. You get the idea.

Please note again that the extent of these changes depends to a great degree on the extent of the diet and the body fat level of the individual: someone dropping from 35% to 30% body fat might see only small changes (or almost none at all) in these parameters, someone who is getting leaner at the 15% range is seeing bigger problems and someone at 5% body fat (e.g. a natural male bodybuilder) is undergoing massive adaptation.

This is a big part of why dieting gets so much harder as people get leaner, muscle loss accelerates, hormones are crashing, etc. My Ultimate Diet 2.0 goes into much more detail on this topic.

Basically, the body undergoes an overall adapatation that attempts to slow fat/weight loss (via reductions in metabolic rate and activity) and seek out food, these adaptations become stronger the leaner the individual gets (you’ll see that this has implications for how to fix it). I’d note that there is more to the overall adaptation to dieting than just the central effects in the brain; for example, impaired conversion of T4 to T3 in the liver is a well known effect of dieting.

Of course, various hormones have other peripheral effects in terms of energy balance and fat loss; for example leptin directly stimulates fat oxidation in skeletal muscle and a known adaptation to fat loss is a decrease in fat oxidation.

There is also that post-starvation hyperphagia I talked about in an earlier post, whereby signals from fat cells drive hunger to extreme levels when food is made available. Which, I’d note is pretty much always in modern society.

Note again (this ties in with my comments above) that the original observation of post-starvation hyperphagia was made in males who were kept on 50% maintenance calories for 6 months, ultimately reaching a body fat percentage of ~5% (that is, the lower limits of human body fat levels). Someone going from 35% to 30% isn’t going to experience nearly that effect and there’s going to be a continuum of responses from fatter to leaner that’s going to occur.

Finally (ok, probably not finally), leptin also impacts on how well or how poorly other appetite hormones in the body send their signals to the brain (that’s in addition to those other hormones sending a signal to the hypothalamus). For example, cholecystokinin (CCK) is a hormone released from the gut primarily in response to protein or fat intake; it’s involved in making you feel full after a meal. As is turns out, in rats at least, CCK doesn’t work as well when leptin is low.

Hardcore dieters (e.g. contest bodybuilders and figure/fitness competitors) are well aware of this: when they start getting very lean, even if they do everything ‘right’ at a given meal (i.e. lots of lean protein, moderate fat, fiber, moderate amounts of low GI carbs), they simply don’t stay full very long. Because all of the short-term fullness signals just aren’t working as well.

That’s because leptin is essentially setting the overall ‘tone’ of the brain in terms of how it responds to other signals. The various hormones that determine when you get hungry or full aren’t working as well when leptin is lowered from dieting and fat loss. Leptin certainly isn’t the only hormone involved in all of this; but it’s definitely one of the most important ones.

Finally, next time, what to do about all of this (short of not dieting and just staying fat and happy).

Read Bodyweight Regulation Part 5

Similar Posts:

Sharing is Caring

Facebook Comments