Fat rats

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Neuroscience—and science in general—is constantly evolving, so older articles may contain information or theories that have been reevaluated since their original publication date.

Do drug development labs need to implement a rodent version of Weight Watchers?

According to a review published 13 June in Chemical Research in Toxicology, the answer is a resounding yes. The review suggests that overfed rodents could be throwing toxicology tests off kilter.

Just as the metabolisms of people who spend their days gorging on doughnuts and cheeseburgers differ from those of people who count their calories, rodents given unlimited access to food apparently have different biochemistry and physiology than those fed regular, limited meals. That can in turn influence the outcomes of toxicology studies.

That’s something for autism researchers to consider as they test potential treatments in rodent models designed to mimic the disorder.

The issue isn’t a new one. According to the review, the Society for Toxicologic Pathology released a position statement a decade ago saying that feeding schedule is an important variable that studies should control for. But nothing much changed, and most rodents still have unlimited access to the equivalent of an all-you-can-eat buffet.

The fact that rats in different labs might eat different amounts at different times might even explain some of the variability seen in rodent toxicology studies, the researchers say.

For example, rodents allowed to eat as much as they want can become obese and develop high levels of cholesterol and triglycerides. What’s more, feeding influences several important biological processes, including circadian clocks, blood sugar regulation and drug metabolism.

All of these issues could be relevant to autism research. Defects in circadian rhythms, for example, have been linked to some autism-related genes. And if drugs being tested for an autism disorder improve an animal’s health by reducing blood sugar problems rather than targeting the true symptoms of the disorder, drug developers might waste precious time and resources developing it.

In fact, the researchers say, scientists may be “unknowingly using a diabetic-type model” of rodents. Given the obesity epidemic in the U.S., that might actually be appropriate. But if so, studying overfed rodents should be an intentional choice rather than a careless one.