As always, no one study settles the argument on this type of debate. This study moves the needle five degrees toward showing that HFCS is metabolically different from equivalent amounts of table sugar.
The study appears in a refereed journal. It includes a strong research design, randomly assigning rats to a treatment (HFCS) group and two control groups.
[Update 3/23: part of the study includes two control groups, which received either plain sucrose or an ordinary rat food diet, so one can distinguish HFCS from sucrose; a comment says that another part of the study included only one control group, which received the rat food diet, so it is not possible to distinguish HFCS from sucrose].
On the other hand, studies in rats are just one element in an array of evidence. Other elements include human studies and describing a plausible biological mechanism. One mystery is how HFCS (55% fructose) could be much different from sucrose (50% fructuse). The conclusion section of the new article spends most of its time talking about the metabolism of fructose, mentioning but then somewhat breezing over the similarity in fructose content between HFCS and sucrose.
Given that sucrose is a disaccharide, which is metabolized to one fructose and one glucose molecule (Caspary, 1992), it has been argued that there is little difference between fructose and sucrose, since both provide about 50% fructose and 50% glucose in the blood stream; and until recently, there was no evidence that HFCS contributes to long-term weight gain beyond what sucrose contributes (Forshee et al., 2007). However, the present study suggests that HFCS and sucrose can have different effects on body weight and obesigenic measures.In each passage above where it seems the authors plan to talk about a mechanism that is specific to HFCS, the subsequent detail turns out to be all about fructose.
HFCS is different than sucrose in many ways. First, HFCS-55 has proportionately slightly more fructose than sucrose (White, 2008). Second, fructose is absorbed further down the intestine than glucose, with much of the metabolism occurring in the liver, where it is converted to fructose-1-phsophate [sic], a precursor to the backbone of the triglyceride molecule (Havel, 2005). Third, fructose is metabolically broken down before it reaches the rate-limiting enzyme (phosphofructokinase), thereby supplying the body with an unregulated source of three-carbon molecules. These molecules are transformed into glycerol and fatty acids, which are eventually taken up by adipose tissue, leading to additional adiposity (Hallfrisch, 1990). And fourth, HFCS causes aberrant insulin functioning, in that it bypasses the insulin-driven satiety system (Curry, 1989). Whereas circulating glucose increases insulin release from the pancreas,... fructose does this less efficiently, because cells in the pancreas lack the fructose transporter.... Typically, insulin released by dietary sucrose inhibits eating and increases leptin release (Saad et al., 1998), which in turn further inhibits food intake. As previously discussed, meals of HFCS have been shown to reduce circulating insulin and leptin levels (Teff et al., 2004). Thus, fructose intake might not result in the degree of satiety that would normally ensue with a meal of glucose or sucrose, and this could contribute to increased body weight.
I enjoyed hearing a talk earlier this month by Barry Popkin (author of The World is Fat). Though he has also speculated about a possible distinct effect of HFCS, he now emphasizes just the sweetness and food energy content.
And this brings me to the final point that I wish news coverage of this topic emphasized more heavily. HFCS is a large part of our food supply, perhaps 40% or more of all caloric sweeteners. In these quantities, a special metabolic effect for HFCS is really beside the point for policy purposes. It could well be true that HFCS is making Americans obese in any case, just because we consume so much of it.