Daniel Engber (who has also done some insightful writing about fat–see for example here and here) has a new series on Slate about lab mice. I’ve only read the first one so far, “The Mouse Trap”–it’s about the limitations of using mice (and almost exclusively mice) to model human diseases. There are particular problems when scientists are not merely studying how a disease works (less direct applications) but trying to develop drugs to treat that disease in humans (more direct applications). The whole article is interesting, and I recommend it, but the part that’s on-topic right now is this part:
It’s been shown that mice living under standard laboratory conditions eat more and grow bigger than their country cousins. …[T]he animals are grouped in plastic cages the size of large shoeboxes, topped with a wire lid and a food hopper that’s never empty of pellets. This form of husbandry, known as ad libitum feeding, is cheap and convenient since animal technicians need only check the hoppers from time to time to make sure they haven’t run dry.
I have to admit, my first thought was, “Is this really so different from how most Americans live?” After all, most of us (with important exceptions including the food-insecure and those currently on a diet) can obtain food whenever we want–we don’t have lab techs rationing out our food. But look at the next sentence:
Without toys or exercise wheels to distract them, the mice are left with nothing to do but eat and sleep—and then eat some more.
I suspect we’d all be eating a lot more if we had so little to occupy ourselves. Your setpoint/settling point is probably going to be a bit different in an environment where you have things to do besides eat and sleep vs. one where you don’t. Still, I wondered how many problems mice in this state would cause researchers when developing drugs for first-world nations–we’re not sitting around with nothing to do but eat and sleep, but we’re not hunter-gatherers, either. As I read more of the article, I discovered that there is at least some evidence that we’re not much like the lab mice:
Twenty years ago, scientists started to develop some new ways to prevent brain damage after a stroke. A neurotransmitter called glutamate had been identified as a toxin for affected nerve cells, and a number of drug companies started working on ways to block its effects…
Now Mattson has an idea for why the drugs didn’t pan out: All the original test-animals were chubby. If there’s something about the brain of an obese, sedentary rodent that amplifies the effects of a glutamate-blocker, that would explain why the drugs worked for a population of lab animals but not in the more diverse set of human patients. This past June, he published a paper confirming the hunch: When he put his test mice on a diet before administering the glutamate-blockers, the drugs’ magical effects all but disappeared.
Many promising treatments could be failing for the same reason, Mattson argues… “There’s some fraction of studies that may have been compromised by [these] issues, but there’s no way to know unless one does the experiment with the proper controls.”
(Note that they only talk about the changes in terms of “chubby” vs. “on a diet” and not in terms of “boredom eating all the time” vs. “limited opportunity for boredom eating”. I don’t blame Engber for writing about it this way; it sounds as though that’s how Mattson conceives of it and how he described it, and Engber is reporting on that. Also note that they were comparing the same mice (or at least the same strain of mice) fed different amounts of food, not genetically different mice that had been fed the same amounts of food but ended up at different weights. So in case anyone was worried, I believe that this doesn’t break HAES.)
Unfortunately, the stroke study was twenty years ago, before human BMI peaked. The typical first-world human lifestyle may show more similarity to that of those mice now. But both Mattson (the scientist interviewed) and Engber seem to think that using sedentary mice that are probably doing a lot of boredom-eating as stand-ins for human beings is still a problem today. If that’s the case, then we’re not as close to a Wall-E-esque fatpocolypse as some people would like to believe.
Also check out the pound mouse: “a laboratory model for obesity, insulin resistance, and fatty liver disease. The Pound Mouse has nonfunctioning receptors for the hormone leptin, which helps to regulate appetite and metabolism.” (I think it’s kinda cute!) I wonder what obesity-and-disease-correlated-with-obesity researchers miss by studying a mouse that is obese for that particular reason, when most obese humans did not become obese due to nonfunctioning leptin receptors. I guess it would depend on to what extent the cause of the disease matters to the way the disease itself behaves. See the obesities concept articulated by Dr. Sharma. (And thanks to DebraSY for bringing it to my attention. DebraSY also wrote the first comment on the “obesities” post–very insightful.)
I sure am going off on tangents today, but I’ve always thought it odd that some people use the existence of the “obesity epidemic” to discount a genetic role in individual weights, when strains of mice like this exist. They usually dismiss genetic differences like these as “extreme cases”, but if an extreme genetic difference can cause an extreme difference in weight, why couldn’t a smaller genetic difference cause a smaller difference in weight?