title: Oleate prevents saturated-fatty-acid-induced ER stress, inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism.
abstract: OBJECTIVE
  Although the substitution of saturated fatty acids with oleate has been recommended in the management of type 2 diabetes mellitus, the mechanisms by which oleate improves insulin resistance in skeletal muscle cells are not completely known. Here, we examined whether oleate, through activation of AMP-activated protein kinase (AMPK), prevented palmitate-induced endoplasmic reticulum (ER) stress, which is involved in the link between lipid-induced inflammation and insulin resistance.
  
  
  METHODS
  Studies were conducted in mouse C2C12 myotubes and in the human myogenic cell line LHCN-M2. To analyse the involvement of AMPK, activators and inhibitors of this kinase and overexpression of a dominant negative AMPK construct (K45R) were used.
  
  
  RESULTS
  Palmitate increased the levels of ER stress markers, whereas oleate did not. In palmitate-exposed cells incubated with a lower concentration of oleate, the effects of palmitate were prevented. The induction of ER stress markers by palmitate was prevented by the presence of the AMPK activators AICAR and A-769662. Moreover, the ability of oleate to prevent palmitate-induced ER stress and inflammation (nuclear factor-kappa B [NF-κB] DNA-binding activity and expression and secretion of IL6) as well as insulin-stimulated Akt phosphorylation and 2-deoxyglucose uptake was reversed in the presence of the AMPK inhibitor compound C or by overexpression of a dominant negative AMPK construct. Finally, palmitate reduced phospho-AMPK levels, whereas this was not observed in oleate-exposed cells or in palmitate-exposed cells supplemented with oleate.
  
  
  CONCLUSIONS
  Overall, these findings indicate that oleate prevents ER stress, inflammation and insulin resistance in palmitate-exposed skeletal muscle cells by activating AMPK.
authors: Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Diagonal 643, 08028 Barcelona, Spain.
authors: L
authors: L
authors: Salvadó
authors: T
authors: T
authors: Coll
authors: A M
authors: AM
authors: Gómez-Foix
authors: E
authors: E
authors: Salmerón
authors: E
authors: E
authors: Barroso
authors: X
authors: X
authors: Palomer
authors: M
authors: M
authors: Vázquez-Carrera
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D008055:Lipids / Q000737:chemistry; D051379:Mice; D032342:Muscle Cells / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology*; D016328:NF-kappa B / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology*; D019308:Palmitic Acid / Q000009:adverse effects* / Q000494:pharmacology; D011753:Pyrones / Q000494:pharmacology; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D001713:Biphenyl Compounds; D008055:Lipids; D016328:NF-kappa B; D011753:Pyrones; D012265:Ribonucleotides; D013876:Thiophenes; D019301:Oleic Acid; D019308:Palmitic Acid; D000620:Aminoimidazole Carboxamide; D000263:Adenylate Kinase; C031143:AICA ribonucleotide; C512408:4-hydroxy-3-(4-(2-hydroxyphenyl)phenyl)-6-oxo-7H-thieno(2,3-b)pyridine-5-carbonitrile