Endothelial Nitric Oxide Synthase (eNOS) Knockout Mice Have Defective Mitochondrial β-Oxidation
Abstract
OBJECTIVE— Recent observations indicate that the delivery of nitric oxide by endothelial nitric oxide synthase (eNOS) is not only critical for metabolic homeostasis, but could also be important for mitochondrial biogenesis, a key organelle for free fatty acid (FFA) oxidation and energy production. Because mice deficient for the gene of eNOS (eNOS−/−) have increased triglycerides and FFA levels, in addition to hypertension and insulin resistance, we hypothesized that these knockout mice may have decreased energy expenditure and defective β-oxidation. RESEARCH DESIGN AND METHODS— Several markers of mitochondrial activity were assessed in C57BL/6J wild-type or eNOS−/− mice including the energy expenditure and oxygen consumption by indirect calorimetry, in vitro β-oxidation in isolated mitochondria from skeletal muscle, and expression of genes involved in fatty acid oxidation. RESULTS— eNOS−/− mice had markedly lower energy expenditure (−10%, P < 0.05) and oxygen consumption (−15%, P < 0.05) than control mice. This was associated with a roughly 30% decrease of the mitochondria content (P < 0.05) and, most importantly, with mitochondrial dysfunction, as evidenced by a markedly lower β-oxidation of subsarcolemmal mitochondria in skeletal muscle (−30%, P < 0.05). Finally, impaired mitochondrial β-oxidation was associated with a significant increase of the intramyocellular lipid content (30%, P < 0.05) in gastrocnemius muscle. CONCLUSIONS— These data indicate that elevated FFA and triglyceride in eNOS−/− mice result in defective mitochondrial β-oxidation in muscle cells.
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NOS3 KO mice have markedly lower energy expenditure and decreases in mitochondrial content and fatty acid oxidation in muscle compared with WT mice.
“Supporting evidence supplied by NOS3 KO mice include a markedly lower energy expenditure and decreases in mitochondrial content and fatty acid oxidation in muscle compared with WT mice [332]”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [332]
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- Authors
- Gouill, E. L., Jimenez, M., Binnert, C., Jayet, P.-Y., Thalmann, S., Nicod, P., Scherrer, U., & Vollenweider, P.
- Affiliations
- University of Lausanne (CH)
- University of Geneva (CH)
- Centre Hospitalier Universitaire Vaudois (CH)
- Department of Internal Medicine and the Botnar Center for Clinical Research, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2007-11-01
- Volume
- 56
- Issue
- 11
- Pages
- 2690-2696
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2135815669
- Semantic Scholar
- 3f4e20b9211807d8b7644916f6840abd5dd643fb
- Cited by
- 130
- References
- 27
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 8 · 2018: 9 · 2017: 6 · 2016: 3 · 2015: 5 · 2014: 9 · 2013: 9 · 2012: 12
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- endothelial nitric oxide synthase, eNOS knockout mice, mitochondrial beta-oxidation, fatty acid oxidation, energy expenditure, oxygen consumption, skeletal muscle mitochondria, intramyocellular lipid, free fatty acids, triglycerides, mitochondrial dysfunction, mitochondrial biogenesis, insulin resistance
- MeSH terms
- Animals, Calorimetry, Indirect, DNA, Mitochondrial, Energy Metabolism, Epididymis, Fatty Acids, Nonesterified, Lipolysis, Male, Mitochondria, Mitochondria, Muscle, Oxidation-Reduction, Oxygen Consumption, Triglycerides, Polymerase Chain Reaction, Mice, Knockout, Muscle, Skeletal, Nitric Oxide Synthase, Body Size, Mice, Nitric Oxide Synthase Type I, Nitric Oxide Synthase Type III
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