Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle lipid peroxidation in the OLETF rat
Abstract
The Otsuka Long-Evans Tokushima fatty (OLETF) rat is a model of hyperphagic obesity in which the animals retain the desire to run voluntarily. Running wheels were provided for 4-wk-old OLETF rats for 16 wk before they were killed 5 h (WL5), 53 h (WL53), or 173 h (WL173) after the wheels were locked. Sedentary (SED) OLETF rats that were not given access to running wheels served as age-matched cohorts. Epididymal fat pad mass, adipocyte volume, and adipocyte number were 58%, 39%, and 47% less, respectively, in WL5 than SED rats. Contrary to cessation of daily running in Fischer 344 × Brown Norway rats, epididymal fat did not increase during the first 173 h of running cessation in the OLETF runners. Serum insulin and glucose levels were 77% and 29% less, respectively, in WL5 than SED rats. Oil red O staining for intramyocellular lipid accumulation was not statistically different among groups. However, lipid peroxidation levels, as determined by total trans-4-hydroxy-2-nonenal (4-HNE) and 4-HNE normalized to oil red O, was higher in epitrochlearis muscles of SED than WL5, WL53, and WL173 rats. mRNA levels of glutathione S-transferase-α type 4, an enzyme involved in cellular defense against electrophilic compounds such as 4-HNE, were higher in epitrochlearis muscle of WL53 than WL173 and SED rats. In contrast, 4-HNE levels in omental fat were unaltered. Epitrochlearis muscle palmitate oxidation and relative transcript levels for peroxisome proliferator-activated receptor-δ and peroxisome proliferator-activated receptor-γ coactivator type 1 were surprisingly not different between runners and SED rats. In summary, voluntary running was associated with lower levels of lipid peroxidation in skeletal muscle without significant changes in intramyocellular lipids or mitochondrial markers in OLETF rats at 20 wk of age. Therefore, even in a genetic animal model of extreme overeating, daily physical activity promotes improved health of skeletal muscle.
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Obesity is primarily prevented in at least two genetically modified obese rodent models by allowing natural, instinctive voluntary running.
“Obesity is primarily prevented in at least two genetically modified, obese rodent models by allowing natural, instinctive voluntary running.”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [355]
Voluntary running prevented obesity and its comorbidities (type 2 diabetes and non-alcoholic fatty liver disease) with no significant reductions of food intake in OLETF rats having a mutant cholecystokinin gene.
“Voluntary running prevented obesity and its comorbidities [T2D and non-alcoholic fatty liver disease] with no significant reductions of food intake in cholecytokinin-1 receptor (OLETF) rats having a mutant cholecystokinin gene (37, 355, 429, 470).”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [355]
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Cites
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Self-citationTargeting Intramyocellular Lipids to Improve Aging Muscle Function
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“For example, high running wheel activity in a rat model of hyperphagic obesity exhibited reduced muscle lipid peroxidation vs. sedentary controls, despite similarly high levels of total muscle lipids [106].”
- Authors
- Morris, R. T., Laye, M. J., Lees, S. J., Rector, R. S., Thyfault, J. P., & Booth, F. W.
- Affiliations
- University of Missouri (US)
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2008-03
- Volume
- 104
- Issue
- 3
- Pages
- 708-715
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2171932917
- Cited by
- 56
- References
- 9
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 1 · 2013: 5 · 2012: 8
- FWCI
- 4.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Otsuka Pharmaceutical
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- OLETF rats, hyperphagic obesity, voluntary running, 4-hydroxynonenal, intramyocellular lipid, hyperinsulinemia, epitrochlearis muscle, PPARδ, PPAR-gamma coactivator 1, mitochondrial function, genetic obesity model
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Adipose Tissue, Aging, Aldehydes, Animals, Blood Glucose, Disease Models, Animal, Eating, Physical Exertion, Glutathione Transferase, Hyperglycemia, Hyperinsulinism, Insulin, Isoenzymes, Male, Mitochondria, Muscle, Obesity, Oxidation-Reduction, Rats, Inbred BN, Rats, Inbred F344, RNA, Messenger, Running, Species Specificity, Superoxide Dismutase, Transcription Factors, Lipid Peroxidation, Weight Gain, RNA-Binding Proteins, Muscle, Skeletal, Palmitic Acid, Rats, Inbred OLETF, PPAR gamma, Rats
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