title: Association between expression of FABPpm in skeletal muscle and insulin sensitivity in intramyocellular lipid-accumulated nonobese men.
abstract: BACKGROUND
  Intramyocellular lipid (IMCL) accumulation is observed in both insulin-resistant subjects and insulin-sensitive endurance athletes (athlete's paradox). We hypothesized that the expression pattern of fatty acid transporters may influence oxidative capacity and determine the association between IMCL and insulin resistance.
  
  
  OBJECTIVE
  The objective of the study was to investigate the muscle expression of fatty acid transporters and their function related to insulin sensitivity in IMCL-accumulated subjects.
  
  
  METHODS
  The study subjects were 36 nonobese healthy men. Their IMCL levels were measured by (1)H-magnetic resonance spectroscopy, and their insulin sensitivity was evaluated by steady-state glucose infusion rate (GIR) during a euglycemic-hyperinsulinemic clamp. Gene expression levels in the vastus lateralis were evaluated by quantitative RT-PCR. We compared the clinical phenotypes and the expression levels of genes involved in lipid metabolism in skeletal muscle between IMCL-accumulated high-GIR (H-GIR) subjects (n = 8) and low-GIR subjects (n = 9). The functions of candidate fatty acid transporters were determined by in vitro analyses.
  
  
  RESULTS
  Compared with the low-GIR group, body fat was lower and maximum oxygen uptake was higher in the H-GIR group. Several lipid oxidation genes in muscle were up-regulated in the H-GIR group, and this was associated with increased expression of higher plasma membrane-associated fatty acid-binding protein (FABPpm) and decreased expression of fatty acid transport protein (FATP)-1. Overexpression of FABPpm in C2C12 myotubes increased fatty acid oxidation coupled with the elevated expression of genes related to fatty acid oxidation. These changes were not observed in FATP1-overexpressed myotubes.
  
  
  CONCLUSIONS
  Differences in the gene expression of fatty acid transporters may, at least in part, affect insulin sensitivity in IMCL-accumulated nonobese men.
authors.affiliation: Department of Metabolism and Endocrinology (M.K., Y.T., S.K., K.T., Y.S., T.W., T.F., F.S., S.I., Y.F., A.K., R.K., H.W.), Sportology Center (Y.T., S.K., S.I., R.K., H.W.), Center for Therapeutic Innovations in Diabetes (H.W.), and Center for Molecular Diabetology (H.W.), Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; and Institute of Health and Sports Science and Medicine (Y.O., N.S., H.N.) and Department of Exercise Physiology (Y.O., N.S., H.N.), Juntendo University Graduate School of Health and Sports Science, Chiba 270-1695, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Tamura
authors.forename: Saori
authors.initials: S
authors.lastname: Kakehi
authors.forename: Kageumi
authors.initials: K
authors.lastname: Takeno
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Takahiro
authors.initials: T
authors.lastname: Watanabe
authors.forename: Takashi
authors.initials: T
authors.lastname: Funayama
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sato
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ikeda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ogura
authors.forename: Norio
authors.initials: N
authors.lastname: Saga
authors.forename: Hisashi
authors.initials: H
authors.lastname: Naito
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujitani
authors.forename: Akio
authors.initials: A
authors.lastname: Kanazawa
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology*; D002478:Cells, Cultured; D050612:Fatty Acid Transport Proteins / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D055815:Young Adult
chemical_list: D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified; C493568:SLC27A1 protein, human; D005947:Glucose