In the first two installments of this series, we covered the "what" and the "how" of leptin. This segment covers a huge amount of information, much of which is fairly complicated, so it will be broken into at least two installments. This one will cover the "why".

As we have discussed briefly, when leptin, the long sought after lipostatic signal, was discovered in 1996, it appeared that the key to solving the epidemic of obesity had been found. Rats with a defect in the gene responsible for its production were profoundly obese, and the administration of recombinant leptin to these rats profoundly decreased food intake and increased energy expenditure as well, resulting in rapid weight loss, which, unlike starvation, was confined solely to adipose tissue -- lean mass was preserved (1). Leptin was quickly anointed as THE anti-obesity hormone (2), and it was only a matter of time and FDA approval before the perfect diet drug would be unleashed upon the gluttonous world.

But, alas, it was not to be. Unfortunately, for the pharmaceutical industry and fat people everywhere, it soon became readily apparent that, rather than suffering from a lack of leptin, obese humans actually exhibited ELEVATED levels (3), thus not only was exogenously administered leptin going to be ineffective as a diet drug, endogenous leptin was not even fulfilling its supposed role as an anti-obesity hormone (4).

Thus, the view of leptin's role shifted, and it is now considered an anti-starvation hormone (5) -- though, it is a lack of leptin, not leptin itself, that sends the starvation signal. It is this role that makes it of paramount importance for the dieting bodybuilder.

Anyone who has dieted for an extended period of time has experienced "hitting the wall", so to speak -- the dreaded slowing, and even complete stoppage, of fat loss.

This is leptin.

Perhaps just as noticeable, or perhaps not -- due to the often fanatical willpower of bodybuilders (or perhaps the fanatical use of EC :) -- is the accompanying increase in appetite, often manifested as true, almost uncontrollable, cravings for food.

This is also leptin.

Then, there is the increased loss of muscle..... And susceptibility to illness..... And fatigue.....

Yep.

Leptin.

Energy Expenditure

Fat loss is sufficiently, if not remarkably, rapid at the beginning of a diet, with two pounds a week being not at all uncommon, even for someone who is fairly lean. However, it soon falls victim to the (not so) wonderful world of evolution. In times of scarcity, the survival advantage of thrifty metabolisms should be fairly self-evident -- Those that had them would be more likely to survive and reproduce than those that needed 5000 calories a day just to keep their skinny asses alive.

Over millions of years, this has become firmly entrenched in the genetic code. Thus, slowly (if you are lucky) but surely, when conditions of scarcity are self-imposed (i.e. when you diet), metabolism, thus fat loss, invariably slows, and if appropriate steps are not taken, it stops completely.

And, just so we do not confine ourselves to anecdotal evidence and conjecture, I will note that, indeed, low leptin levels have been found to be correlated with decreases in resting energy expenditure (6, 7, 8), and the administration of recombinant leptin corrects this in animals with defects in leptin production, as well as preventing or reversing the decline seen with fasting (9).