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Mitochondrial oxygen affinity predicts basal metabolic rate in humans
Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.ORCID iD: 0000-0002-1343-8656
Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.ORCID iD: 0000-0002-4030-5437
Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
2011 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 25, no 8, 2843-52 p.Article in journal (Refereed) Published
Abstract [en]

The basal metabolic rate (BMR) is referred to as the minimal rate of metabolism required to support basic body functions. It is well known that individual BMR varies greatly, even when correcting for body weight, fat content, and thyroid hormone levels, but the mechanistic determinants of this phenomenon remain unknown. Here, we show in humans that mass-related BMR correlates strongly to the mitochondrial oxygen affinity (p50(mito); R(2)=0.66, P=0.0004) measured in isolated skeletal muscle mitochondria. A similar relationship was found for oxygen affinity and efficiency during constant-load submaximal exercise (R(2)=0.46, P=0.007). In contrast, BMR did not correlate to overall mitochondrial density or to proton leak. Mechanistically, part of the p50(mito) seems to be controlled by the excess of cytochrome c oxidase (COX) protein and activity relative to other mitochondrial proteins. This is illustrated by the 5-fold increase in p50(mito) after partial cyanide inhibition of COX at doses that do not affect maximal mitochondrial electron flux through the ETS. These data suggest that the interindividual variation in BMR in humans is primarily explained by differences in mitochondrial oxygen affinity. The implications of these findings are discussed in terms of a trade-off between aerobic efficiency and power.

Place, publisher, year, edition, pages
2011. Vol. 25, no 8, 2843-52 p.
National Category
Medical and Health Sciences
Research subject
Medicine/Technology
Identifiers
URN: urn:nbn:se:gih:diva-1913PubMedID: 21576503OAI: oai:DiVA.org:gih-1913DiVA: diva2:448129
Note
At the time of Filip Larsens dissertation the article was accepted, not yet published.Available from: 2011-10-14 Created: 2011-10-14 Last updated: 2017-03-31Bibliographically approved
In thesis
1. Dietary inorganic nitrate: role in exercise physiology, cardiovascular and metabolic regulation
Open this publication in new window or tab >>Dietary inorganic nitrate: role in exercise physiology, cardiovascular and metabolic regulation
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Nitric oxide (NO) is a ubiquitous signaling molecule with a vast number of tasks in the body, including regulation of cardiovascular and metabolic function. A decreased bioavailability of NO is a central event in disorders such as hypertension and metabolic syndrome. NO is also important in the regulation of blood flow and metabolism during exercise. The production of NO has previously been thought to be under the exclusive control of the nitric oxide synthases (NOS) but this view is now being seriously challenged. Recent lines of research suggest the existence of an NO-synthase independent pathway in which the supposedly inert NO oxidation products nitrate (NO3-) and nitrite (NO2-) can be reduced back to NO in blood and tissues. An important additional source of nitrate is our everyday diet and certain vegetables are particularly rich in this anion. In this thesis the possibility that dietary derived nitrate is metabolized in vivo to form reactive nitrogen oxides with NO-like bioactivity has been explored. It is shown that nitrate in amounts easily achieved via the diet, increases the systemic levels of nitrite and reduces blood pressure in healthy humans. Moreover, nitrate reduces whole body oxygen cost during submaximal and maximal exercise; a surprising effect involving improvement in mitochondrial efficiency and reduced expression of specific mitochondrial proteins regulating proton conductance. Alterations in the mitochondrial affinity for oxygen can explain this reduction in both submaximal and maximal oxygen consumption and predicts basal metabolic rate in humans. Finally, in mice lacking endothelial NO synthase, dietary supplementation with nitrate could reverse several features of the metabolic syndrome that develop in these animals. These studies demonstrate that dietary nitrate can fuel a nitrate-nitrite-NO pathway with important implications for cardiovascular and metabolic functions in health and disease.

Place, publisher, year, edition, pages
Solna: Karolinska Institutet, 2011
National Category
Medical and Health Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-2079 (URN)978-91-7457-397-8 (ISBN)
Public defence
2011-06-17, Aulan Farmakologen, Nanna Svartz väg 2, Solna, 09:00 (English)
Opponent
Supervisors
Note
Avhandling vid Karolinska Institutet och Gymnastik- och idrottshögskolan, GIHAvailable from: 2012-01-09 Created: 2012-01-09 Last updated: 2016-08-08Bibliographically approved

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Larsen, FilipEkblom, BjörnSahlin, Kent

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