OK, we've talked about the general case for paleo and the carbohydrate hypothesis. Next up is the fructose hypothesis.
All carbs are not created equal. The single biggest change to the modern American diet is the vast quantity of sugar that we consume, mostly in the form of sucrose and high fructose corn syrup (which are pretty interchangeable from a dietary standpoint). The amount of fructose thus consumed is unprecedented in human history. Fructose is metabolized differently from other monosaccharides and it is especially able to cause leptin sensitivity issues, which can lead to obesity and insulin sensitivities as well (metabolic syndrome and diabetes). You can find populations that eat a lot of carbs, but do not have obesity, diabetes, and breast cancer (the Japanese) - the main dietary difference seems to be the amount of sugar consumed. The leading proponent of this hypothesis is Robert Lustig, who has a hit YouTube video and a talk at the Ancestral Health Symposium (AHS). He has convinced (I think) Gary Taubes that this idea has merit and Taubes has written an excellent article on it and discussed it at the recent AHS.
What do I think? The idea certainly has merit. I know fat people who don't consume that much sugar and sugar addicts who aren't fat, so the story probably isn't quite that simple. We really do consume an appalling amount of sugar and it is pretty easy to blame at least some of the modern ills on sugar (gout and more). It seems quite plausible that fructose is responsible for the obesity epidemic. Cutting out fructose is probably not enough to make you skinny if your metabolism is screwed up and it probably is. But maybe cutting way back could prevent our children from suffering the same fate.
Notice again that a paleo diet protects you completely if this hypothesis is true.