How so? Because the seats are 2x3? Since Douglas designed the aircraft to seat in a 2x3 (or 3x2) pattern, no. It's not going to tip on its side or fatigue faster because there is one more seat on whatever side of the plane. In the grand scheme things on that aircraft, the weight differential from one side to the other is negligible. This isn't like sticking a whole bunch of weight on one side of your car. Far more important (especially on the MD-80s) is the CG and the mean aerodynamic chord limits. On empty flights, they'll often have to stick some ballast up in the front hold to bring the CG forward.

I have a MD-80 aircraft handbook lying around somewhere. I'll have to dig it out and see if they even mention this. However, seeing how there are still hundreds of DC-9 variants still flying, I'd say fatigue due to the 2x3 seating is highly unlikely.