title: Insulin resistance syndrome blunts the mitochondrial anabolic response following resistance exercise.
abstract: Metabolic risk factors associated with insulin resistance syndrome may attenuate augmentations in skeletal muscle protein anabolism following contractile activity. The purpose of this study was to investigate whether or not the anabolic response, as defined by an increase in cumulative fractional protein synthesis rates (24-h FSR) following resistance exercise (RE), is blunted in skeletal muscle of a well-established rodent model of insulin resistance syndrome. Four-month-old lean (Fa/?) and obese (fa/fa) Zucker rats engaged in four lower body RE sessions over 8 days, with the last bout occurring 16 h prior to muscle harvest. A priming dose of deuterium oxide ((2)H(2)O) and (2)H(2)O-enriched drinking water were administered 24 h prior to euthanization for assessment of cumulative FSR. Fractional synthesis rates of mixed (-5%), mitochondrial (-1%), and cytosolic (+15%), but not myofibrillar, proteins (-16%, P = 0.012) were normal or elevated in gastrocnemius muscle of unexercised obese rats. No statistical differences were found in the anabolic response of cytosolic and myofibrillar subfractions between phenotypes, but obese rats were not able to augment 24-h FSR of mitochondria to the same extent as lean rats following RE (+14% vs. +28%, respectively). We conclude that the mature obese Zucker rat exhibits a mild, myofibrillar-specific suppression in basal FSR and a blunted mitochondrial response to contractile activity in mixed gastrocnemius muscle. These findings underscore the importance of assessing synthesis rates of specific myocellular subfractions to fully elucidate perturbations in basal protein turnover rates and differential adaptations to exercise stimuli in metabolic disease.
authors.affiliation: Dept. of Health and Kinesiology, Texas A & M University, College Station, 77843-4243, USA.
authors.forename: Mats I
authors.initials: MI
authors.lastname: Nilsson
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Greene
authors.forename: Justin P
authors.initials: JP
authors.lastname: Dobson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Wiggs
authors.forename: Heath G
authors.initials: HG
authors.lastname: Gasier
authors.forename: Brandon R
authors.initials: BR
authors.lastname: Macias
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Shimkus
authors.forename: James D
authors.initials: JD
authors.lastname: Fluckey
mesh_terms: D000818:Animals; D015331:Cohort Studies; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D009119:Muscle Contraction / Q000502:physiology; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D011924:Rats, Zucker; D018709:Statistics, Nonparametric
chemical_list: D024101:Mitochondrial Proteins; D009124:Muscle Proteins