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Are Your Rats (and Mice) Too Fat?
Maybe the phrase is so ubiquitous that you never thought twice about it: ad libitum. Free access to food and water has become so standard in our labs in the past few decades, ad libitum is now a resident phrase in virtually every Methods section of every animal research paper. But, does constant access to food and water create the proper conditions to model disease? Dr. Mark Mattson would argue that it may not. His work focuses on the neurodegenerative diseases of aging, including Alzheimer’s, Parkinson’s, Huntington’s diseases, and stroke. One of his focuses within this field is the protective effects of caloric restriction against these diseases.
In 2010, Martin et al. published a paper in PNAS explaining that mice and rats maintained in industry-standard environments, with ad libitum-feeding and little to no environmental enrichment, become obese and in time will generate the plethora of health problems that go with obesity, including diabetes and renal failure. They then cite several lines of evidence that a restricted diet in laboratory rodents could safeguard from the onset of disease, and increase overall lifespan. For example, adipose tissue itself can produce a chronic, low-grade inflammatory state in animals by increasing levels of circulating cytokines. Some cancer types were more likely to proliferate in overweight and sedentary animals versus calorie-restricted animals. In transgenic mouse models of Alzheimer’s disease, animals with calorie-restricted diets and environmental enrichment developed pathology in memory processing slower than their standard-housed (ad libitum-fed without enrichment) counterparts.
The main implication of this research is that perhaps our overweight and sedentary mouse and rat models are not properly mirroring human beings, as we expect them to. The authors of the study suggest that this may explain, in part, why so many experimental compounds that make it to clinical trials in humans end up failing. The inverse of this may even be true: perhaps compounds that do not work in obese animals may actually work in humans with normal weights, but never reach clinical trial. Then again, since the population of much of the world has indeed become generally overweight and sedentary, is our standard ad libitum model completely valid for some disorders?
What do you think?
Have you given consideration to the feeding regimen of your animals? Is free access to food a valid feeding regimen? Should the presence of environmental enrichment be named in the Methods section of research articles?
Martin B, Ji S, Maudsley S, Mattson MP. (2010). “Control” laboratory rodents are metabolically morbid: why it matters. Proc Natl Acad Sci U S A. Apr 6;107(14):6127-33.
Engber D. (2011). The Mouse Trap. Slate.com. Nov 15.