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

Authors

  • Matteo Ricchi,

    1. Dipartimento Integrato di Medicina Interna, Endocrinologia, Metabolismo & Geriatria – Università degli Studi di Modena e Reggio Emilia,
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  • Maria Rosaria Odoardi,

    1. Dipartimento Integrato di Medicina Interna, Endocrinologia, Metabolismo & Geriatria – Università degli Studi di Modena e Reggio Emilia,
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  • Lucia Carulli,

    1. Dipartimento Integrato di Medicina Interna, Endocrinologia, Metabolismo & Geriatria – Università degli Studi di Modena e Reggio Emilia,
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  • Claudia Anzivino,

    1. Dipartimento Integrato di Medicina Interna, Endocrinologia, Metabolismo & Geriatria – Università degli Studi di Modena e Reggio Emilia,
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  • Stefano Ballestri,

    1. Dipartimento Integrato di Medicina Interna, Endocrinologia, Metabolismo & Geriatria – Università degli Studi di Modena e Reggio Emilia,
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  • Adriano Pinetti,

    1. Dipartimento di Chimica, Università di Modena e Reggio Emilia,
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  • Luca Isaia Fantoni,

    1. Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Università degli Studi di Modena e Reggio Emilia, Modena,
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  • Fabio Marra,

    1. Dipartimento di Medicina Interna and Center for Research, Transfer, and High Education DENOTHE, Università di Firenze, Firenze, and
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  • Marco Bertolotti,

    1. Dipartimento Integrato di Medicina Interna, Endocrinologia, Metabolismo & Geriatria – Università degli Studi di Modena e Reggio Emilia,
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  • Sebastiano Banni,

    1. Dipartimento di Biologia Sperimentale, Università degli Studi di Cagliari, Cagliari, Italy
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  • Amedeo Lonardo,

    1. Dipartimento Integrato di Medicina Interna, Endocrinologia, Metabolismo & Geriatria – Università degli Studi di Modena e Reggio Emilia,
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  • Nicola Carulli,

    Corresponding author
    1. Dipartimento Integrato di Medicina Interna, Endocrinologia, Metabolismo & Geriatria – Università degli Studi di Modena e Reggio Emilia,
      Nicola Carulli and Paola Loria, Università degli Studi di Modena, Dipartimento di Medicina Interna, Endocrinologia, Metabolismo e Geriatria, Nuovo Ospedale Civile Sant’Agostino Estense di Baggiovara, Via Giardini Baggiovara, Modena 41100, Italy. Email: paola.loria@unimore.it
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  • Paola Loria

    Corresponding author
    1. Dipartimento Integrato di Medicina Interna, Endocrinologia, Metabolismo & Geriatria – Università degli Studi di Modena e Reggio Emilia,
      Nicola Carulli and Paola Loria, Università degli Studi di Modena, Dipartimento di Medicina Interna, Endocrinologia, Metabolismo e Geriatria, Nuovo Ospedale Civile Sant’Agostino Estense di Baggiovara, Via Giardini Baggiovara, Modena 41100, Italy. Email: paola.loria@unimore.it
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  • Partly supported by grants from MIUR Ministero Istruzione Università e Ricerca Scientifica -PRIN 2004061213_001.

Nicola Carulli and Paola Loria, Università degli Studi di Modena, Dipartimento di Medicina Interna, Endocrinologia, Metabolismo e Geriatria, Nuovo Ospedale Civile Sant’Agostino Estense di Baggiovara, Via Giardini Baggiovara, Modena 41100, Italy. Email: paola.loria@unimore.it

Abstract

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.

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