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Gnaiger 2019 MiP2019
Coupling states OXPHOS  +
Diseases Obesity  +
Has abstract [[Image:MITOEAGLE-logo.jpg|left|100px|link
[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]] “''Preventable diseases are strongly related to a sedentary life style. These are spreading world-wide at an epidemic scale. Mitochondrial dysfunction is increasingly associated with the progression of such pathologies: cause or consequence? There is currently no regimented, quantitative system, or database organized to routinely test, compare and monitor mitochondrial capacities within individuals, populations, or among populations. This reflects the need for scientific innovation and represents a shortcoming in the health system of our modern, rapidly aging society''” (MitoEAGLE COST Action application). The working groups of the COST Action CA15203 have made substantial progress towards meeting the mission of Mitochondrial Fitness Mapping (Fig. 1). The present communication (''1'') provides an example of harmonization of datasets published by different research laboratories on OXPHOS capacity in isolated mitochondria and permeabilized fibers obtained from biopsies of human skeletal muscle (''vastus lateralis''); (''2'') emphasizes the importance of comparative protocol harmonization projects and reproducibility studies; (''3'') illustrates the necessity and difficulty of defining objective exclusion criteria and applying quality assessment of published data; (''4'') links muscle mitochondrial fitness to whole body aerobic fitness; (''5'') discusses the extension of tissue-specific to systemic mitochondrial fitness from muscle to brain; and (''6'') documents the added value of Open Access data repositories. Analogous to ergometric measurement of ''V''<sub>O2max</sub> on a cycle or treadmill, cell ergometry is based on measurement of OXPHOS-capacity, ''J''O<sub>2,P</sub> [pmol O<sub>2</sub>·s<sup>-1</sup>·mg<sup>-1</sup>] equivalent to [µmol O<sub>2</sub>·s<sup>1</sup>·kg<sup>1</sup>], at the mitochondrial level. The main datasets on OXPHOS capacity of isolated mitochondria or permeabilized muscle fibers, harmonization algorithms, and exclusion criteria applied in the present analysis have been reviewed ten years ago [1]. Only a few more studies based on high-resolution respirometry published since then were integrated, exclusively on Caucasian healthy controls [2,3]. This 'MitoEAGLE database 1' is intended to initiate a comprehensive review by the MitoEAGLE Working Group 2 (skeletal muscle). Harmonization introduces potential biases with a scope of improvement based on updated evaluation of (1) wet/dry mass ratios applicable to studies reporting dry mass only; (2) flux control ratios applied to calculate combined NADH- and succinate-linked OXPHOS capacities from data limited to the NADH-pathway or succinate-pathway capacities measured separately; (3) temperature adjustment for measurements at temperatures different from 37 °C [4]; (4) oxygen limitation of measurements with permeabilized fibers that are performed at or below air saturation [5]; (5) OXPHOS capacities reported without evaluation of saturating concentrations of ADP, P<sub>i</sub>, and fuel substrates, or without concern of stable steady-state fluxes; and (6) potential bias when results are reported without details on instrumental O<sub>2</sub>-background tests, calibrations, and corresponding corrections. Recent trends of an increasing body mass index (BMI) of the human population indicate an epidemic prevalence of obesity in many countries despite the fact that underweight remains the dominant problem in the world’s poorest regions [6]. Extending the concept of the ‘Reference Man’ [7], a healthy reference population (HRP) is defined with a large range of body height (standing height, ''h'') and corresponding reference body mass, ''m''°, reference ''V''<sub>O2max</sub>°, and mitochondrial fitness parameters ('''Fig. 2'''). The reference mass/height relationship constitutes a basic component of the concept of the HRP, obtained from >17.000 measurements on healthy people reported between 1931 and 1944 before the fast food and soft drink epidemic, with about half of the reported measurements ranging from 1.2 to 1.8 m corresponding to ''m''° of 22 to 68 kg and ''h''/''m''<sup>0.35</sup> [8] ('''Fig. 2a'''). The [[body mass excess]], BME, is defined as the actual body mass, ''m'', relative to the reference body mass, ''m''°, at the same height ('''Suppl. Tab. S1'''). Deviations of ''m'' versus ''m''° are due to weight gain without height gain. The similar displacement of men and women (Norwegian HUNT 3 study [9]) from the HRP line is consistent with the increase of average BMI in Norway during the past decades [6]. ('''Fig. 2a'''). BME>1 (excess) yields a more consistent index of overweight and obesity across a large range of body heights compared to the BMI ('''Fig. 2b'''). Similarly, BME<1 (not shown) indicates a body mass deficit which is insufficiently reflected by the BMI at different body heights. Mitochondrial OXPHOS capacity per mass of vastus lateralis declines as a power function of BME ('''Fig. 2c'''). ''V''<sub>O<small>2</small>max/BM</sub> can be modeled as a function of (''1'') the metabolically inactive (compared to ''V''<sub>O<small>2</small>max</sub>) body mass added to a person at height ''h'', (''2'') the decline of mitochondrial capacity per muscle mass as a consequence of an inactive lifestyle and increased body mass, and (''3'') a slight increase of muscle mass with increasing BME as a ‘weight lifting effect’ ('''Fig. 2d'''). Taken together, the BME has a strong conceptual foundation on the level of large scale population statistics and is linked to lifestyle and mitochondrial fitness. Importantly, the BME has a straightforward understandable meaning that is easy to communicate to the general public on the personal level: you are overweight if your body mass is increased by 20 to 25 % relative to the reference body mass determined by your height. The consequences of mitochondrial control on ''V''<sub>O<small>2</small>max/BM</sub> will be discussed in terms of mechanistic explanations of a large range of neurodegenerative diseases related to the passive lifestyle with an increased BME [10].
sive lifestyle with an increased BME [10].  +
Has editor [[Gnaiger E]]  + , [[Plangger M]]  + , [[Tindle-Solomon L]]  +
Has publicationkeywords aerobic capacity - VO2max per body mass  + , body mass excess - BME  + , body mass index - BMI  + , healthy reference population - HRP  + , mitochondrial fitness  +
Has title [[Image:Erich Gnaiger.jpg|left|90px|Erich Gnaiger]] OXPHOS capacity in human muscle tissue and body mass excess – the MitoEAGLE mission towards an integrative database (Version 4; 2019-10-23).  +
Instrument and method Oxygraph-2k  +
Mammal and model Human  +
MiP area Exercise physiology;nutrition;life style  + , Gender  + , Respiration  + , mt-Biogenesis;mt-density  + , mt-Medicine  +
Pathways NS  +
Preparation Intact organism  + , Isolated mitochondria  + , Permeabilized tissue  +
Tissue and cell Skeletal muscle  +
Was published by MiPNetLab AT Innsbruck Gnaiger E + , AT Innsbruck Oroboros +
Was submitted in year 2019  +
Was submitted to event MiP2019/MitoEAGLE Belgrade RS +
Was written by Gnaiger E +
Categories Abstracts
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
21:29:18, 25 October 2019  +
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