Cardiovascular risk factors emerge after artificial selection for low aerobic capacity.
Abstract
In humans, the strong statistical association between fitness and survival suggests a link between impaired oxygen metabolism and disease. We hypothesized that artificial selection of rats based on low and high intrinsic exercise capacity would yield models that also contrast for disease risk. After 11 generations, rats with low aerobic capacity scored high on cardiovascular risk factors that constitute the metabolic syndrome. The decrease in aerobic capacity was associated with decreases in the amounts of transcription factors required for mitochondrial biogenesis and in the amounts of oxidative enzymes in skeletal muscle. Impairment of mitochondrial function may link reduced fitness to cardiovascular and metabolic disease.
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Rat selection experiments support the idea that evolution could select for high aerobic capacity.
“provided experimental evidence that natural selection for high aerobic capacity during evolution is a feasible concept (569).”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [569]
After 11 generations of selecting rats by running distance, the high-distance line had 58% greater aerobic capacity than the low-distance line.
“Selection of rats on the basis of the longest or shortest running distances during a single exercise test resulted in selection of a 58% higher aerobic capacity in the high-distance line than the short-distance line over 11 generations.”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [569]
High-VO2max rats showed better cardiovascular and metabolic profiles: lower 24-hour blood pressure, improved acetylcholine-induced vasorelaxation, lower fasting glucose, less visceral fat, lower triglycerides, and more mitochondrial protein.
“Rats with high VO2max had healthier cardiovascular systems (12% lower mean 24-hr blood pressures and 48% better acetylcholine-induced vasorelaxation), and healthier metabolic risk factors (16% less fasting plasma glucose, 39% less visceral adipose tissue, 63% lower plasma triglyceride levels, and greater mitochondrial protein concentrations).”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [569]
In rats bred for low aerobic capacity over multiple generations, expression of several OXPHOS genes is markedly reduced, even in the absence of obesity.
“Similarly, in rats bred for low aerobic capacity over multiple generations, expression of several OXPHOS genes is markedly reduced, even in the absence of obesity (134).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [134]
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- Authors
- Wisløff, U., Najjar, S. M., Ellingsen, Ø., Haram, P. M., Swoap, S., Al-Share, Q., Fernström, M., Rezaei, K., Lee, S. J., Koch, L. G., & Britton, S. L.
- Affiliations
- Norwegian University of Science and Technology (NO)
- Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Olav Kyrres gt. 3, 7489 Trondheim, Norway.
- Corresponding author
- Wisløff, Ulrik
- Najjar, Sonia M.
- ORCID
- Venue
- Science
- Published
- 2005-01-21
- Volume
- 307
- Issue
- 5708
- Pages
- 418-420
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2138553207
- Cited by
- 657
- References
- 17
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 12 · 2023: 15 · 2022: 11 · 2021: 20 · 2020: 14 · 2019: 23 · 2018: 28 · 2017: 28 · 2016: 39 · 2015: 48 · 2014: 27 · 2013: 47 · 2012: 42
- FWCI
- 122.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r21dk057497-02)
- National Heart, Lung, and Blood Institute (HL64270, R01HL064270)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK54254, R01DK054254, DK57497)
- National Center for Research Resources (RR 17718, R24RR017718)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- selective breeding, cardiorespiratory fitness, cardiovascular risk factors, metabolic syndrome, mitochondrial biogenesis, oxidative enzymes, skeletal muscle, mitochondrial function, exercise capacity, disease risk, rats
- MeSH terms
- Adipose Tissue, Aerobiosis, Aging, Animals, Blood Pressure, Body Weight, Breeding, Cardiovascular Diseases, Disease Models, Animal, Endothelium, Vascular, Physical Exertion, Female, Glucose Tolerance Test, Humans, Hypertension, Insulin, Insulin Resistance, Lipids, Male, Mitochondria, Muscle, Oxidation-Reduction, Oxygen Consumption, Physical Conditioning, Animal, Risk Factors, Running, Selection, Genetic, Exercise, Trans-Activators, Ventricular Function, Left, Exercise Tolerance, Muscle, Skeletal, Metabolic Syndrome, PPAR gamma, Rats
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