title: Expression of genes involved in fatty acid transport and insulin signaling is altered by physical inactivity and exercise training in human skeletal muscle.
abstract: Physical deconditioning is associated with the development of chronic diseases, including type 2 diabetes and cardiovascular disease. Exercise training effectively counteracts these developments, but the underlying mechanisms are largely unknown. To gain more insight into these mechanisms, muscular gene expression levels were assessed after physical deconditioning and after exercise training of the lower limbs in humans by use of gene expression microarrays. To exclude systemic effects, we used human models for local physical inactivity (3 wk of unilateral limb suspension) and for local exercise training (6 wk of functional electrical stimulation exercise of the extremely deconditioned legs of individuals with a spinal cord injury). The most interesting subset of genes, those downregulated after deconditioning as well as upregulated after exercise training, contained 18 genes related to both the "insulin action" and "adipocytokine signaling" pathway. Of these genes, the three with strongest up/downregulation were the muscular fatty acid-binding protein-3 (FABP3), the fatty acid oxidizing enzyme hydroxyacyl-CoA dehydrogenase (HADH), and the mitochondrial fatty acid transporter solute carrier 25 family member A20 (SLC25A20). The expression levels of these genes were confirmed using RT-qPCR. The results of the present study indicate an important role for a decreased transport and metabolism of fatty acids, which provides a link between physical activity levels and insulin signaling.
authors.affiliation: Dept. of Physiology, Radboud Univ. Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Gerwen
authors.initials: G
authors.lastname: Lammers
authors.forename: Fleur
authors.initials: F
authors.lastname: Poelkens
authors.forename: Noortje T L
authors.initials: NT
authors.lastname: van Duijnhoven
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Pardoel
authors.forename: Joost G
authors.initials: JG
authors.lastname: Hoenderop
authors.forename: Dick H J
authors.initials: DH
authors.lastname: Thijssen
authors.forename: Maria T E
authors.initials: MT
authors.lastname: Hopman
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics / Q000378:metabolism; D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D015444:Exercise / Q000502:physiology*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D055815:Young Adult
chemical_list: D054392:Adipokines; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D026901:Membrane Transport Proteins; D012313:RNA; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human; C120109:SLC25A20 protein, human