What are the obstacles to "refitting" the human body's metabolism?

Question

As a layman, I understand the problem of rising obesity like this:

• In the old times, humans could never get enough food, thus they would eat whatever they could get. This "program" is encoded in our genes.

• At least in industrial countries, the ubiquity of energy-rich food makes some of us get obese, at least partial because we follow this old "program".

I hope I didn't get it too wrong. Now my question is this:

Would it be possible to somehow "rig" the human body to change the metabolism and make it fit to a rather sedentary lifestyle?

For example: Instead of storing surplus food / energy within the body, it could be excreted, thus keeping humans at their weight even when eating a lot more than they need.

Could this be possible? Which organs/hormones control the utilization of food within the human body and can they be influenced in such a way?

Answer 1

Yes, you got it right. The theory you're referring to is called the thrifty gene hypothesis. There have been several attempts at "rigging" metabolism to reduce the amount of surplus calories stored as fat, as you suggest, and some of them have gone all the way to approved drugs.

One strategy is to block intestinal absorption of nutrients, so that excess food is simply excreted. Perhaps the most well known example is Orlistat, a prescription drug that prevents fat absorption by inhibiting lipases secreted by the pancreas. This has been proven (somewhat) effective in clinical trials, but also causes gastrointestinal problems like oily stool. Most drugs of this type, preventing the gut from doing normal digestion, will probably have this limitation.

There are also ideas about increasing metabolism of absorbed nutrients to "burn" more calories. Generally, utilization of nutrients in the body does not happen on its own; it is a consequence of activating other energy-demanding processes, like muscle contraction, brain activity, immune system function, and so on. And any attempt to increase metabolism, regardless of mechanism, will end up generating more heat. So in order to increase metabolism, it is necessary to turn on some heat-generating function (other than exercise :) Some research groups are experimenting with increasing energy expenditure in brown fat (a type of fat that normally oxidized nutrients to generate heat) to burn off excess nutrients. This is still a long way from medical use though.