title: Antagonism Between Saturated and Unsaturated Fatty Acids in ROS Mediated Lipotoxicity in Rat Insulin-Producing Cells.
abstract: OBJECTIVE
  Elevated levels of non-esterified fatty acids (NEFAs) are under suspicion to mediate β-cell dysfunction and β-cell loss in type 2 diabetes, a phenomenon known as lipotoxicity. Whereas saturated fatty acids show a strong cytotoxic effect upon insulin-producing cells, unsaturated fatty acids are not toxic and can even prevent toxicity. Experimental evidence suggests that oxidative stress mediates lipotoxicity and there is evidence that the subcellular site of ROS formation is the peroxisome. However, the interaction between unsaturated and saturated NEFAs in this process is unclear.
  
  
  METHODS
  Toxicity of rat insulin-producing cells after NEFA incubation was measured by MTT and caspase assays. NEFA induced H2O2 formation was quantified by organelle specific expression of the H2O2 specific fluorescence sensor protein HyPer.
  
  
  RESULTS
  The saturated NEFA palmitic acid had a significant toxic effect on the viability of rat insulin-producing cells. Unsaturated NEFAs with carbon chain lengths >14 showed, irrespective of the number of double bonds, a pronounced protection against palmitic acid induced toxicity. Palmitic acid induced H2O2 formation in the peroxisomes of insulin-producing cells. Oleic acid incubation led to lipid droplet formation, but in contrast to palmitic acid induced neither an ER stress response nor peroxisomal H2O2 generation. Furthermore, oleic acid prevented palmitic acid induced H2O2 production in the peroxisomes.
  
  
  CONCLUSIONS
  Thus unsaturated NEFAs prevent deleterious hydrogen peroxide generation during peroxisomal β-oxidation of long-chain saturated NEFAs in rat insulin-producing cells.
authors.affiliation: From the Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Gehrmann
authors.forename: Wiebke
authors.initials: W
authors.lastname: Würdemann
authors.forename: Thomas
authors.initials: T
authors.lastname: Plötz
authors.forename: Anne
authors.initials: A
authors.lastname: Jörns
authors.forename: Sigurd
authors.initials: S
authors.lastname: Lenzen
authors.forename: Matthias
authors.initials: M
authors.lastname: Elsner
mesh_terms: D000818:Animals; D001681:Biological Assay; D002470:Cell Survival / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066292:Lipid Droplets / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019301:Oleic Acid / Q000494:pharmacology*; D019308:Palmitic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D020675:Peroxisomes / Q000187:drug effects* / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D019301:Oleic Acid; D019308:Palmitic Acid; D006861:Hydrogen Peroxide