Why Leptin Isn't a Blockbuster Weight-Loss Drug
As I have said before, I want to point all of my readers interested in diet and health to Peter Attia’s podcasts (“The Drive”). Peter and I have similar perspectives, and where we differ, I agree with him rather than myself.
One way in which I can contribute, even given what Peter has done with his podcast is by shining a spotlight on a few key things in the wealth of information Peter and his guests provide.
In #33, Peter’s interview with Rudy Leibel, I was fascinated by their discussion of why Leptin did not turn out to be the blockbuster weight-loss drug that Pharma hoped it would be. There is a mechanistic reason and an evolutionary reason.
Mechanistically, very low levels of leptin make people want to eat more. But above-normal levels of leptin don’t make people want to eat less. (The same is true for rodents, where this was first discovered.)
Evolutionarily, Peter Attia and Rudy Leibel agreed that signaling when an individual has too little body fat is a much more pressing evolutionary problem than signaling when an individual has too much. So it isn’t terribly surprising that leptin is designed to signal when there is too little body fat by low leptin levels and doesn’t do much of anything to signal when there is too much body fat—especially high leptin levels aren’t treated is much of a signal at all.
In order to signal that there is enough body fat, leptin is a hormone for fat cells to call out “I’m here.” As long as the roll call of fat cells is adequate, the body doesn’t do much with even higher leptin levels.
For those rare individuals who have leptin deficiency, administering leptin can indeed cure obesity. But for most people who are overweight or obese, leptin deficiency is not the problem. There are examples of things which can be the cure of a problem even if they have little to do with the cause. (For example, deep negative interest rates can cure aggregate demand problems caused by deleveraging.) Leptin is not one of them: it only cures obesity if lack of leptin is the cause of that obesity.
Update March 16, 2021: Later on in the podcast, there is a hint that leptin might be helpful in maintaining weight loss. The muscles of those who had lost weight seemed to become more metabolically efficient, thereby burning fewer calories. Leptin injections, presumably by creating the illusion to the body of more body fat than was actually there, resulted in less increase in the metabolic efficiency of the muscles.
But even if this is, in fact, helpful in maintaining weight loss, I have wondered if greater metabolic efficiency of healthy cells combined with regular fasting might be an important cancer preventative, since greater metabolic efficiency of healthy cells increases their metabolic advantage over cancer cells, which are typically metabolically handicapped.
For annotated links to other posts on diet and health, see:
There is a section of links on anti-cancer eating that are relevant to the March 16, 2021 update above.