title: Fatty acid transporters involved in the palmitate and oleate induced insulin resistance in primary rat hepatocytes.
abstract: OBJECTIVE
  To determine the presence and possible involvement of FAT/CD36, FABPpm and FATP-2, transporters in (i) fatty acids movement across plasma membrane and (ii) an induction of insulin resistance by palmitic (PA) and oleic (OA) fatty acids in primary hepatocytes.
  
  
  METHODS
  Primary hepatocytes were treated with either PA and OA or combination of activators (AICAR, Insulin) or inhibitors (SSO, phloretin) of FA transport. Expression of FA and glucose transporters as well as insulin signalling proteins was determined using Western blot analyses. Palmitate and glucose transport was measured using radioactive isotopes. Intracellular lipid content [ceramide, diacylglycerols (DG) and triacylglycerols] and FA composition were estimated by GLC.
  
  
  RESULTS
  In primary hepatocytes, adding phloretin diminished insulin, and AICAR stimulated palmitate transport. Both PA and OA fatty acids induced the protein expression of FAT/CD36 and FATP-2 with concomitant: (i) reduction in GLUT-2 protein content, (ii) inhibition of insulin-stimulated glucose uptake, (iii) reduction in insulin-stimulated activation of AKT and GSK, (iv) accumulation of either DG (PA and OA) or ceramide (only PA).
  
  
  CONCLUSIONS
  FA transport into hepatocytes is, at least in part, protein-mediated process, and both PA and OA induce the protein expression of FAT/CD36 and FATP-2. Both saturated (PA) and unsaturated (OA) fatty acids induce insulin resistance in primary hepatocytes, associated with the accumulation of DG and/or ceramide.
authors.affiliation: Department of Physiology, Medical University of Bialystok, Bialystok, Poland. adrian@umwb.edu.pl
authors.forename: A
authors.initials: A
authors.lastname: Chabowski
authors.forename: M
authors.initials: M
authors.lastname: Żendzian-Piotrowska
authors.forename: K
authors.initials: K
authors.lastname: Konstantynowicz
authors.forename: W
authors.initials: W
authors.lastname: Pankiewicz
authors.forename: A
authors.initials: A
authors.lastname: Mikłosz
authors.forename: B
authors.initials: B
authors.lastname: Łukaszuk
authors.forename: J
authors.initials: J
authors.lastname: Górski
mesh_terms: D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D018955:CD36 Antigens / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000378:metabolism; D050612:Fatty Acid Transport Proteins / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D019301:Oleic Acid / Q000378:metabolism / Q000633:toxicity*; D010168:Palmitates / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018955:CD36 Antigens; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; C515999:Got2 protein, rat; D010168:Palmitates; D019301:Oleic Acid; D003066:Coenzyme A Ligases; C553239:Slc27a2 protein, rat