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On the basis of these traits, we here hypothesise that the regulation of mitochondrial networks in skeletal muscle is hampered in humans with compromised oxidative capacity and insulin sensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a cross-sectional design, we compared four groups of participants (selected from previous studies) ranging in aerobic capacity and insulin sensitivity, i.e. participants with type 2 diabetes (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200911), obese participants without diabetes (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912), lean individuals (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910) and endurance-trained athletes (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912); basal, overnight fasted muscle biopsies were newly analysed for the current study and we compared the levels of essential mitochondrial dynamics and quality control regulatory proteins in skeletal muscle tissue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Type 2 diabetes patients and obese participants were older than lean participants and athletes (58.6\u2009\u00b1\u20094.0 and 56.7\u2009\u00b1\u20097.2 vs 21.8\u2009\u00b1\u20092.5 and 25.1\u2009\u00b1\u20094.3\u00a0years,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001, respectively) and displayed a higher BMI (32.4\u2009\u00b1\u20093.7 and 31.0\u2009\u00b1\u20093.7 vs 22.1\u2009\u00b1\u20091.8 and 21.0\u2009\u00b1\u20091.5\u00a0kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001, respectively) than lean individuals and endurance-trained athletes. Fission protein 1 (FIS1) and optic atrophy protein 1 (OPA1) protein content was highest in muscle from athletes and lowest in participants with type 2 diabetes and obesity, respectively (FIS1: 1.86\u2009\u00b1\u20090.79 vs 0.79\u2009\u00b1\u20090.51\u00a0AU,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002; and OPA1: 1.55\u2009\u00b1\u20090.64 vs 0.76\u2009\u00b1\u20090.52\u00a0AU,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.014), which coincided with mitochondrial network fragmentation in individuals with type 2 diabetes, as assessed by confocal microscopy in a subset of type 2 diabetes patients vs endurance-trained athletes (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096). Furthermore, lean individuals and athletes displayed a mitonuclear protein balance that was different from obese participants and those with type 2 diabetes. Mitonuclear protein balance also associated with heat shock protein 60 (HSP60) protein levels, which were higher in athletes when compared with participants with obesity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.048) and type 2 diabetes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002), indicative for activation of the mitochondrial unfolded protein response. Finally, OPA1, FIS1 and HSP60 correlated positively with aerobic capacity (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.48,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0001;\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.55,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001 and\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.61,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001, respectively) and insulin sensitivity (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.40,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.008;\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.44,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003 and\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.48,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Collectively, our data suggest that mitochondrial dynamics and quality control in skeletal muscle are linked to oxidative capacity in humans, which may play a role in the maintenance of muscle insulin sensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial registry<\/jats:title>\n                    <jats:p>numbers NCT00943059, NCT01298375 and NL1888<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-020-05335-w","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T12:25:03Z","timestamp":1606739103000},"page":"424-436","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity"],"prefix":"10.1007","volume":"64","author":[{"given":"Alexandre","family":"Houzelle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna A.","family":"J\u00f6rgensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert","family":"Schaart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Daemen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nynke","family":"van Polanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciar\u00e1n E.","family":"Fealy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthijs K. 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