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Induction of endoplasmic reticulum stress by palmitate may contribute to insulin‐resistance in HepG2 cell lines
Author(s) -
Cho HyangKi,
Lee Jinyoung,
Kwon Young Hye
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1054-c
Subject(s) - lipotoxicity , insulin resistance , medicine , endoplasmic reticulum , endocrinology , unfolded protein response , saturated fatty acid , insulin , adipocyte protein 2 , chemistry , fatty acid , biology , biochemistry
Recent studies indicate that high levels of free fatty acids (FFAs) and adipokines may be main causes of obesity‐related insulin‐resistance in fat, liver and muscle tissues. However, the molecular mechanism linking FFAs to the inhibition of insulin action remain unclear. Endoplasmic reticulum (ER) stress has been shown to be involved in the development of type 2 diabetes due to the metabolic and inflammatory stresses of obesity. Here, we treated HepG2 cell lines with either saturated fatty acid (palmitate) or unsaturated fatty acid (oleate) and we observed that lipotoxicity was induced by palmitate. Palmitate treatment significantly induced ER stress in HepG2 cell lines, as indicated by increased levels of X box‐binding protein (XBP)‐1 mRNA splicing and C/EBP homologous transcription factor (CHOP) expression. Palmitate treatment also significantly activated c‐jun N terminal kinase (JNK) and decreased protein kinase B (Akt) phohsphorylation, suggesting ER stress‐mediated JNK activation may be involved in insulin resistance in the liver. Therefore, these data demonstrate that high level of saturated fatty acid induces lipotoxicity and insulin‐resistance by mediation of ER stress in the liver.