What is Wrong with Obesity Research

This paper in Nature Communications 14-3-3ζ Coordinates Adipogenesis of Visceral Fat has garnered some attention in the popular press. It is also a perfect example of what is wrong with the way modern obesity research is conducted and reported. This paper finds a protein that regulates adipogenesis or fat cell production. I haven't gone into details of the results but let's just assume that it is correct. The problem is that the authors and the press then make the statement that this provides a possible drug target for obesity. Why is this a problem? Well consider the analogy with a car. The gas tank represents the adipocytes, - it is the store of energy. Now, you find a "gene" that shrinks the gas tank and then publish in Nature Automobiles and the press release states that that you have found a potential treatment for car obesity. If it is really true that the car (mouse) still takes in the same amount of petrol (food) as before, then where did this excess energy go? The laws of thermodynamics must still hold. The only possibilities are that your gas mileage went down (energy expenditure increased) or the energy is being stored in some other auxiliary gas tank (liver?). A confounding problem is that rodents have very high metabolic rates compared to humans. They must eat a significant fraction of their body weight each day just to stay alive. Deprive a mouse or rat of food for a few days and it will expire. The amount of energy going into fat storage per day is a small amount by comparison. It is difficult to measure food intake precisely enough to resolve whether or not two rats are eating the same thing and most molecular biology labs are not equipped to make these precise measurements nor understand that they are necessary. One rat needs to only eat more by a small amount to gain more weight. If two cars (mice) grow at different weights then the only two possible explanations is that they have different energy expenditures or they are eating different amounts. Targeting the gas tank (adipocytes) simply does not make sense as a treatment of obesity. It might be interesting from the point of view of understanding development or even cancer but not weight gain. I have argued in the past that if you find that you have too much gas in the car then the most logical thing to do is to put less gas in the car, not to drive faster so you burn up the gas. If you are really interested in understanding obesity, you should try to understand appetite and satiety because that has the highest leverage for affecting body weight.