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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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March 3, 2010

Fat Rats Make Poor Test Subjects?

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Posted by Derek

Well, here's a brow-furrowing paper, courtesy of PNAS. Th authors, from the National Institute on Aging, contend that most laboratory rodents are overfed, under-stimulated, and are (to use their phrase) "metabolically morbid". This affects their suitability as control and experimental animals for a wide variety of assays.

There seem to be effects across the board - the immune system, glucose and lipid handling, cardiovascular numbers, susceptibility to tumors, cognitive performance. The list is a long one, and the route causes seem to be ad libitum feeding and lack of exercise. The beneficial effects of some drugs in rodent models, the authors propose, could be due (at least in part) to their ability to reverse the artificial conditions that the animals are maintained under, and the application of these results to the real world could be doubtful. (The same concerns don't apply nearly as much to larger animals such as dogs and primates. They're handled differently, and their physiologies don't seem to be altered, or at least nowhere near as much).

Of course, some people live similar lifestyles, as far as the lack of activity and ad libitum feeding goes, so I have to wonder about the rodents being better test animals than one might wish for. But overall, this seems like a useful wake-up call to the animal testing community, especially in some therapeutic areas. On a domestic level, I'm thinking through the implications of this for the two guinea pigs my children have - they seem to sit around and eat all the time. The guinea pigs, I mean, not the kids.

Comments (9) + TrackBacks (0) | Category: Animal Testing


COMMENTS

1. sgcox on March 3, 2010 10:08 AM writes...

Authors noticed that too:

"The standard overfed sedentary control animal is a
good model for an increasing fraction of human subjects who are overweight and sedentary,..."

Permalink to Comment

2. Vader on March 3, 2010 10:34 AM writes...

Yes, I've seen a lot of blubbering over this report.

---------------------------------------------->

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3. Anne on March 3, 2010 11:06 AM writes...

I don't know about your guinea pigs or lab rats, but the gerbils I grew up with sound downright frenetic by comparison - they'd shred cereal boxes within minutes, and they were constantly running in their wheel.

Permalink to Comment

4. Aspirin on March 3, 2010 1:54 PM writes...

-but the gerbils I grew up with sound downright frenetic by comparison

By 'gerbils' do you mean human beings who behaved like gerbils or actual gerbils?

Permalink to Comment

5. AR on March 3, 2010 2:14 PM writes...

Fat rats ... reminds of running maximum tolerated dose (MTD) tox studies in rodents. For the unknowing, one version of the MTD mixes drug in with rat chow and allow ad libitum feeding.

In such studies nearly all drugs are efficacious obesity drugs. The compound class or therapeutic intent is not important matter just as long as it smells or tastes foul. The rats would not eat.

We just need to get people to salt their food with the drugs we make.

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6. Jacko on March 3, 2010 4:51 PM writes...

Rodents are bad models period!

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7. RKN on March 3, 2010 6:12 PM writes...

An interesting report, thanks for the link.

I don't think it's so much that sedentary rats are bad controls, per se, but whether or not they really represent "wild type." I'm highly suspicious that any animal in tightly controlled captivity has a wild type gene expression pattern, and the reasons go beyond merely whether they are fed ad libitum or not.

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8. RenegadeSci on March 3, 2010 10:29 PM writes...

This is old news, and what I thought much of the caloric restriction data showed. I'm not even convinced that the primate caloric restriction studies have shown much more than how much moderate obesity can shorten your life.

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9. lazybratsche on March 5, 2010 11:54 AM writes...

I mentioned this to my fiancee, who worked as a vet tech in a university mouse facility, and she mentioned that ad libitum feeding is simply cheap and easy. It takes an animal tech a lot less time to just top off the food on a semi-regular basis. Measuring out food every day for every cage takes a lot more time and manual labor, and would thus cost a lot more. Plus that introduces the risk that someone will forget to feed the mice one day; my fiancee mentioned that this happened once every few weeks for the calorie restricted mice.

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