Physics is still relevant. The only way to lose weight (outside of surgery) is to spend more energy than you take in. The problem, of course, is that your energy intake and your energy output are functions of each other plus a lot of other things besides (including what's on your mind). I still think that for most people (aka with an uninformative prior) the advice of "Eat less, move more" is a good starting point. Given more data, adjust as needed.

I'm pretty sure "Force feeding yourself as much fat as you can keep down with the aid of anti-emetics, taking glucose intravenously while injecting insulin, estrogen and testosterone and taking a β2 antagonist" is closer to "exactly the wrong thing to do".