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Property "Has-20abstract" (as page type) with input value "The-20skeletal-20muscle-20of-20severely-20obese-20inspaniduals-20(BMI-20-3E-2040-20kg-2Fm2)-20is-20characterized-20by-20a-20depressed-20ability-20to-20oxidize-20fatty-20acids-20and-20a-20failure-20to-20upregulate-20fatty-20acid-20oxidation-20(FAO)-20in-20response-20to-20increased-20lipid-20availability,-20both-20of-20which-20may-20contribute-20to-20a-20positive-20lipid-20balance-20and-20weight-20gain.-20The-20inability-20to-20switch-20from-20predominately-20glucose-20oxidation-20to-20FAO-20in-20the-20presence-20of-20a-20lipid-20challenge,-20such-20as-20a-20high-2Dfat-20diet-20(HFD),-20is-20part-20of-20a-20defect-20in-20obesity-20known-20as-20metabolic-20inflexibility.-20In-20severe-20obesity,-20ten-20consecutive-20days-20of-20aerobic-20training-20(short-2Dterm-20training)-20partially-20restores-20metabolic-20flexibility-20by-20increasing-20the-20ability-20of-20skeletal-20muscle-20to-20oxidize-20fatty-20acids.-20The-20purpose-20of-20this-20dissertation-20was-20to-20determine-20a)-20whether-20contractile-20activity-20in-20human-20primary-20skeletal-20muscle-20cell-20culture-20(HSkMC)-20via-20electrical-20stimulation-20provides-20a-20model-20to-20investigate-20the-20mechanisms-20underlying-20the-20ability-20of-20short-2Dterm-20aerobic-20training-20to-20normalize-20FAO-20and-20provide-20some-20degree-20of-20metabolic-20flexibility-20in-20severely-20obese-20inspaniduals-20and-20b)-20whether-20the-20metabolic-20inflexibility-20present-20in-20obesity-20is-20unique-20to-20a-20lipid-20challenge-20such-20as-20a-20HFD-20or-20whether-20obese-20inspaniduals-20are-20also-20metabolically-20inflexible-20when-20challenged-20with-20carbohydrates-20(CHO)-20such-20as-20galactose-20or-20pyruvate.-20The-20hypotheses-20were-20that-201)-20HSkMC-20would-20provide-20a-20model-20to-20investigate-20how-20-27-27in-20vivo-27-27-20contractile-20activity-20increases-20FAO-20and-20markers-20of-20mitochondrial-20content-20in-20response-20to-20short-2Dterm-20aerobic-20training-20and-202)-20HSkMC-20from-20severely-20obese-20inspaniduals-20would-20be-20metabolically-20flexible-20in-20response-20to-20galactose-20or-20pyruvate-20but-20would-20remain-20metabolically-20inflexible-20to-20a-20lipid-20challenge.-20The-20results-20contained-20herein-20suggest-20that-20contractile-20activity-20in-20HSkMC-20for-2048-20h-20may-20be-20capable-20of-20mimicking-20some-20of-20the-20short-2Dterm-20training-20effects-20such-20as-20increased-20FAO-3B-20however,-20a-20longer-20electrical-20stimulation-20period-20is-20warranted-20to-20initiate-20changes-20in-20mitochondrial-20content-20and-20oxidative-20capacity.-20Although-20comparisons-20between-20lean-20and-20obese-20were-20not-20made-20in-20this-20study,-20the-20results-20and-20recommendations-20of-20the-20present-20investigation-20have-20laid-20the-20groundwork-20for-20future-20studies-20to-20investigate-20the-20effect-20of-20electrical-20stimulation-20on-20HSkMC-20established-20from-20severely-20obese-20inspaniduals.-20-20-20In-20the-20second-20study-20of-20this-20investigation,-20HSkMC-20established-20from-20severely-20obese-20inspaniduals-20were-20found-20to-20be-20metabolically-20flexible-20in-20response-20to-2024-20h-20incubations-20with-20lipid,-20galactose,-20or-20pyruvate-20as-20evidenced-20by-20an-20increase-20in-20state-203-20palmitoyl-2Dcarnitine-20malate-20(PCM3)-20and-20FCCP-20stimulated-20respiration-20in-20response-20to-20all-20three-20substrates.-20Citrate-20synthase-20activity-20and-20OXPHOS-20protein-20content-20also-20increased-20whereas-20glucose-20utilization-20decreased-20in-20response-20to-20substrate-20challenges-20in-20both-20lean-20and-20obese-20groups.-20The-20volunteers-20in-20the-20second-20study-20were-20young-20and-20likely-20not-20far-20into-20the-20progression-20of-20metabolic-20disease,-20which-20may-20explain-20why-20metabolic-20flexibility-20remained-20intact-20in-20this-20population.-20Although-20limited-20by-20the-20inability-20to-20fully-20recapitulate-20true-20physiological-20conditions,-20human-20primary-20skeletal-20muscle-20culture-20is-20a-20novel-20tool-20for-20investigations-20into-20the-20mechanisms-20underlying-20metabolic-20inflexibility-20in-20obesity." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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