Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes

Background and Aim:  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 w...

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Published in:Journal of gastroenterology and hepatology 2009-05, Vol.24 (5), p.830-840
Main Authors: Ricchi, Matteo, Odoardi, Maria Rosaria, Carulli, Lucia, Anzivino, Claudia, Ballestri, Stefano, Pinetti, Adriano, Fantoni, Luca Isaia, Marra, Fabio, Bertolotti, Marco, Banni, Sebastiano, Lonardo, Amedeo, Carulli, Nicola, Loria, Paola
Format: Article
Language:English
Subjects:
apoptosis
Apoptosis - drug effects
Biological and medical sciences
cell culture techniques
Cell Line, Tumor
Dose-Response Relationship, Drug
fatty acids
fatty liver
Fatty Liver - chemically induced
Fatty Liver - genetics
Fatty Liver - metabolism
Fatty Liver - pathology
Fatty Liver - prevention & control
Gastroenterology. Liver. Pancreas. Abdomen
Gene Expression Regulation - drug effects
Hepatocytes - drug effects
Hepatocytes - metabolism
Hepatocytes - pathology
Humans
Insulin - metabolism
insulin resistance
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Oleic Acid - metabolism
Oleic Acid - toxicity
Other diseases. Semiology
Palmitic Acid - metabolism
Palmitic Acid - toxicity
PPAR alpha - genetics
PPAR gamma - genetics
Receptor, Insulin - metabolism
RNA, Messenger - metabolism
saturated and insaturated
Signal Transduction - drug effects
Sterol Regulatory Element Binding Protein 1 - genetics
Triglycerides - metabolism
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Summary:Background and Aim:  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 PPARγ 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 PPARα 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.
ISSN:0815-9319
1440-1746
DOI:10.1111/j.1440-1746.2008.05733.x