Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine . All content is Derek’s own, and he does not in any way speak for his employer.

Here’s a weird and interesting paper to think about. There’s an unfortunately clear trend in human populations towards obesity, which seems to have been especially noticeable over the last thirty years or so. (I believe that the average-thinnest US state today would have been the fattest state in 1980, just to give one vivid example). And it’s not just the US – other areas of the world have shown similar trends. All sorts of causes have been advanced – greater availability of high-calorie-content food can’t be ignored, perhaps less physical activity overall, and there’s been a search throughout all sorts of dietary factors.

But this new paper isn’t looking at the human population at all:

We examined samples collectively consisting of over 20 000 animals from 24 populations (12 divided separately into males and females) of animals representing eight species living with or around humans in industrialized societies. In all populations, the estimated coefficient for the trend of body weight over time was positive (i.e. increasing). The probability of all trends being in the same direction by chance is 1.2 × 10−7. Surprisingly, we find that over the past several decades, average mid-life body weights have risen among primates and rodents living in research colonies, as well as among feral rodents and domestic dogs and cats.

Hmm. There are still a lot of confounding variables here, but this is, um, food for thought. The authors did exclude a number of the more obviously problematic groups:

We excluded datasets (i) consisting solely of terminal or late-life weights because weight loss often occurs towards the end of life, and presages death, and population differences in late-life weights are often not representative of population differences in weight during earlier adulthood; (ii) consisting of animals that, during the period considered, were known or were likely to have been exposed to deliberate selection for phenotypes related to weight or adiposity (effectively ruling out livestock); (iii) consisting of animals that were calorically restricted or had their food intake titrated to maintain relatively constant body weights; and (iv) uniformly exposed to suspected toxins or drugs (e.g. the treatment groups from toxicology programmes).

And after that, all 24 populations studied (12 animal datasets, male and female) still show definite trends towards increasing weight. If you combine the genders and look at the 12 populations, the trend still holds, with a p-value of 0.000049. And it’s true that p-values can be misused and can be misleading, but at that level, you should assume that there’s something going on.

Our findings reveal that large and sustained population increases in body weights can occur in mammalian populations, just as they have occurred among human populations, even in the absence of those factors that are typically conceived of as the primary determinants of the human obesity epidemic via their influence on diet (e.g. access to vending machines) and physical activity (e.g. less physical education classes in schools)

Now, feral rats could be chowing down on a greater abundance of rich food in the available garbage, but that doesn’t explain the upwards creep in ad libitum fed research animal weights. And perhaps better (or more indulgent) care explains the increase in domestic dogs and cats, but that doesn’t apply to the wild rats. And so on – as the authors take care to point out, there’s no reason a priori that a single explanation should apply across all these populations, but when you see this noticeable a trend across so many groups, you would also be remiss not to speculate about one. You can go off track by seeking overarching explanations, but you can go off track by trying to treat everything as a special case, too.

If there is a single cause behind all this, you’re looking at (among other things) the possibility of endocrine disruption from some environmental contaminant (or contaminants), or perhaps some factor of that sort affecting epigenetic signaling pathways, or even an infectious agent. All of these have been thought about in the past, but other explanations have always seemed more plausible. This paper, though, does. . .well, I was about to say “put some more weight behind such theories”, but you know what I mean. What would make an interesting comparison would be the weights of animals over this period that have little or no human contact, but those are probably hard data points to get.

A side effect of this work is that every crackpot in the world will now use it to show why their pet theory is clearly the real explanation. The paper has only been out for a few days, but get braced – it’s coming. But we may still end up with a real explanation that’s not what we would have bet on. I await more research in this area with interest.