If I'm on a IFR flight plan with appropriate IFR reserves, and I'm given a lower altitude which will consume more fuel, what should I do?
As I said in my comment, I don't think there's any single answer to this question because there are just too many variables and the scenario itself seems a little artificial.

But, the first thing you can do is negotiate with ATC. Accept the descent instruction but request a return to FL250 as soon as possible. Offer to fly at another altitude (including above FL250 if possible), or on an alternative route, or with a 10-degree course deviation or anything else that gives ATC options for keeping you at the altitude you want. Of course, there's still no guarantee that the controller will be able to allow it.

The next thing would be fuel management: depending on the aircraft and your current power settings, you may be able to sacrifice speed in order to gain range. But that might not help either if the end result is still that you won't have the reserves you need.

If none of those those things are possible then there's no good option except to plan a fuel stop. Declaring an emergency would be an abuse of the system and could lead to an investigation: you have plenty of fuel, just not enough to get where you want to go, and there's no immediate danger to the aircraft. (I read an NTSB ruling where a pilot had repeatedly said "unable" and eventually declared an emergency simply in order to keep on his preferred route. The FAA grounded him, he appealed to the NTSB and lost.)

In fact, you hopefully already planned for a possible fuel stop because if the winds are so different at FL210 and FL250 that it makes the difference between making it to your destination or not, that's something you should have found out during flight planning. But even if you didn't, or if the wind just changed suddenly, a diversion for fuel shouldn't be a big deal.