title: Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes.
abstract: OBJECTIVE
  Studies have shown monounsaturated oleic acid to be less toxic than palmitic acid and to prevent/attenuate palmitic acid hepatocites toxicity in steatosis models in vitro. However, to what degree these effects are mediated by steatosis extent is unknown.
  
  
  METHODS
  We evaluated whether steatosis per se is associated with hepatocytes apoptosis and determined the role of oleic and palmitic acid, the most abundant fatty acids in western diets, on triglyceride accumulation and apoptosis in an in vitro model of steatosis induced in three hepatocytic cell lines (HepG2, HuH7, WRL68). The impact of incubation for 24 h with oleic (0.66 and 1.32 mM) and palmitic acid (0.33 and 0.66 mM), alone or combined (molar ratio 2 : 1) on steatosis, apoptosis, and insulin signalling, was evaluated.
  
  
  RESULTS
  Concurrent with PPARgamma and SREBP-1 gene activation, steatosis extent was larger when cells were treated with oleic than with palmitic acid; the latter fatty acid was associated with increased PPARalpha expression. Cell apoptosis was inversely proportional to steatosis deposition. Moreover, palmitic, but not oleic acid, impaired insulin signalling. Despite the higher amount of fat resulting from incubation of the two fatty acids combined, the apoptosis rate and impaired insulin signalling were lower than in cells treated with palmitic acid alone, indicating a protective effect of oleic acid.
  
  
  CONCLUSIONS
  Oleic acid is more steatogenic but less apoptotic than palmitic acid in hepatocityc cell cultures. These data may provide a biological basis for clinical findings on dietary patterns and pathogenetic models of nonalcoholic fatty liver disease.
authors.affiliation: Dipartimento Integrato di Medicina Interna, Endocrinologia, Metabolismo & Geriatria, Università degli Studi di Modena e Reggio Emilia, Modena, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Ricchi
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Odoardi
authors.forename: Lucia
authors.initials: L
authors.lastname: Carulli
authors.forename: Claudia
authors.initials: C
authors.lastname: Anzivino
authors.forename: Stefano
authors.initials: S
authors.lastname: Ballestri
authors.forename: Adriano
authors.initials: A
authors.lastname: Pinetti
authors.forename: Luca Isaia
authors.initials: LI
authors.lastname: Fantoni
authors.forename: Fabio
authors.initials: F
authors.lastname: Marra
authors.forename: Marco
authors.initials: M
authors.lastname: Bertolotti
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Banni
authors.forename: Amedeo
authors.initials: A
authors.lastname: Lonardo
authors.forename: Nicola
authors.initials: N
authors.lastname: Carulli
authors.forename: Paola
authors.initials: P
authors.lastname: Loria
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D019301:Oleic Acid / Q000378:metabolism / Q000633:toxicity*; D047493:PPAR alpha / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D019308:Palmitic Acid / Q000378:metabolism / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D007328:Insulin; D047493:PPAR alpha; D047495:PPAR gamma; D012333:RNA, Messenger; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D019301:Oleic Acid; D019308:Palmitic Acid; D011972:Receptor, Insulin