Excellent journal club presentation today by Marcus Seldin, a 2nd-year Physiology PhD student in the Wong lab.

He presented two papers: one from 2007 entitled "Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity", and one from 2010 entitled "Gene knockout of Acc2 has little effect on body weight, fat mass, or food intake".

As you can tell from the title, these two papers exemplify the so-called "decline effect".

So what happened?  A possible explanation is that the first "knockout" actually made a truncated protein that acted as a dominant negative, but one of the professors present preferred to take the Occam's Razor interpretation (probably because Dr. Wakil wouldn't lend him his mice).  It is tantalizing to imagine what Dr.s Cline and Shulman make of the whole thing.

I really admire PNAS for publishing that second paper: imagine how many sad graduate students would be laboring to attempt to repeat the first group's work (especially if they're stingy with sharing their mice) and then blaming themselves for not being able to reproduce it, all in parallel, were it not for this paper.  Thank you, PNAS, for recognizing that negative results are just as valid as positive results (so long as the experiment is well-designed, of course, but that goes for positive results just as much as negative ones), and an integral part of the scientific experience.