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Tissue\u2010specific IS was measured using a four\u2010phase hyperinsulinemic\u2010euglycemic clamp with glucose and glycerol isotope tracers to assess suppression of endogenous glucose release and lipolysis by insulin. Intramyocellular lipid content was assessed by <jats:sup>1<\/jats:sup>H\u2013magnetic resonance spectroscopy, and hepatic fat fraction (HFF) and visceral fat were assessed by magnetic resonance imaging. Calf\u2010muscle mitochondrial activity was measured with exercise\u2010stimulated <jats:sup>31<\/jats:sup>P\u2013magnetic resonance spectroscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Youth with obesity had higher HFF (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), visceral fat (<jats:italic>P<\/jats:italic>\u2009=\u20090.024), and intramyocellular lipid content (<jats:italic>P<\/jats:italic>\u2009=\u20090.017) and lower muscle (glucose clearance rate [<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001]), adipose (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001), and hepatic IS (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.003). Mitochondria postexercise response was not different. In participants with obesity, muscle IS inversely correlated with HFF (<jats:italic>r<\/jats:italic>\u2009=\u20090.700, <jats:italic>P<\/jats:italic>\u2009=\u20090.002) and suppressed free fatty acid concentrations (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.65, <jats:italic>P<\/jats:italic>\u2009=\u20090.003).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Inactive normoglycemic youth with obesity had decreased muscle, adipose, and hepatic IS. Free fatty acids and liver fat were inversely associated with muscle IS, which argues for lipid\u2010targeted interventions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/oby.22658","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T06:10:23Z","timestamp":1572329423000},"page":"2046-2054","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Muscle Insulin Resistance in Youth with Obesity and Normoglycemia is Associated with Altered Fat Metabolism"],"prefix":"10.1002","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1593-1695","authenticated-orcid":false,"given":"Melanie","family":"Cree\u2010Green","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology Department of Pediatrics University of Colorado Anschutz Medical Campus Aurora Colorado USA"},{"name":"Barbara Davis Center for Childhood Diabetes University of Colorado Anschutz Medical Campus Aurora 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