Since this is such an emotional topic, I wanted to challenge myself to try and par it down to bare bones etiquette.
Leaving out issues of fat and bullying, etc., IMHO it comes down to this:
1) It is rude to comment negatively on another person's appearance. You are foisting your unwanted and unasked-for opinion on them. At worst you are insulting them and at best you are wasting their time by pointing out something they already know and have no desire to be reminded of.
2) Since this behavior (rude and/or unhelpful comments) is not acceptable, the simplest, most basic response (if you choose to respond instead of ignore) would be corrective:
You don't have to defend yourself, you don't have to argue, you don't have to justify why you are the way you are. You excuse them their ignorant behavior and alert them of the rudeness that has escaped their mouth like the uncouth belch the phrase is usually a response to. Brain-to-mouth "burps", whether done with malicious intent out a car window or out of misplaced "concern" by a friend or family member, are to be excused as inappropriate and then best forgotten. They do not deserve any further effort or thought on your part.
"Excuse you." can be said coldly, neutrally, calmly, or cheerfully. Repeat ad nauseum as necessary.
I only came up with this today but I plan on using it the next time someone says something to me.