I am not a chemist, but one of my CAD students was and he explained what the difference is, and it is on a very small scale that ultimately has a big effect. The way I understood what he said is: HFCS is a 5 carbon chain while cane/natural sugar is a 6 carbon chain. Your body breaks them down and deals with these carbons in pairs. That means with the HFCS, no matter what you do, 20% of it is not easily processed by the body. Instead of being able to be stored for later use like the other two pairs, the one orphaned has no immediate use and so it basically becomes fat.
*That does not mean natural sugar is good for you
It just isn't as bad.