Animal models of complex diseases: an initial strategy.
We speculated that the rise in atmospheric oxygen from 2 billion years ago was so integral for the evolution of biocomplexity that it must also associate strongly with complex diseases. As a remote test of this idea, we hypothesized that lines contrasting for disease and health would emerge from artificial selection for low and high aerobic treadmill running capacity. Eleven generations of selection in rats produced lines that differed by 347% in running capacity. The low line demonstrated health risk factors including higher visceral adiposity, blood pressure, insulin, and triglycerides. The high line was superior for VO2max, economy of running, heart function, and nitric oxide-induced vascular dilation.
Britton
Steven Loyal
SL
Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, Michigan 48109, USA. brittons@med.umich.edu
Koch
Lauren Gerard
LG
D000273:Adipose Tissue; D000332:Aerobiosis; D000818:Animals; D005075:Biological Evolution; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004734:Energy Metabolism; D015444:Exercise; D006801:Humans; D007328:Insulin / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D010101:Oxygen Consumption; D010805:Physical Conditioning, Animal; D051381:Rats; D012307:Risk Factors; D012420:Running; D012641:Selection, Genetic; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D007328:Insulin; D014280:Triglycerides; D009569:Nitric Oxide