Full-length adiponectin protects hepatocytes from palmitate-induced apoptosis via inhibition of c-Jun NH2 terminal kinase

Tae W. Jung, Yong J. Lee, Myung W. Lee, Seon M. Kim

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Hepatic apoptosis is elevated in patients with non-alcoholic steatohepatitis and is correlated with the severity of the disease. Long-chain saturated fatty acids, such as palmitate, induce apoptosis in liver cells. The present study examined adiponectin-mediated protection against saturated fatty acid-induced apoptosis in the human hepatoma cell line, HepG2. Cells were cultured in a control media (i.e. without fatty acids) or the same media containing 250 μmol·L-1 of albumin-bound oleate or palmitate for 24 h. The adiponectin concentrations used were: 0, 1, 10 or 100 μg·mL-1 (n = 4-6 per treatment). Palmitate and thapsigargin, but not oleate, activated caspase-3 and decreased cell viability in the absence of adiponectin. Adiponectin reduced palmitate- and thapsigargin-induced activation of caspase-3 and cell death in a dose-dependent manner. Phosphatidylinositol 3-kinase and AMP-activated protein kinase inhibitors abolished the effects of adiponectin. Adiponectin-induced inhibition of palmitate- and thapsigargin-induced apoptosis was not the result of an augmentation in the unfolded protein response or the increased expression of genes encoding the inhibitor of apoptosis proteins, inhibitor of apoptosis protein-2 and X-linked mammalian inhibitor of apoptosis protein. Palmitate and thapsigargin, but not oleate, increased c-Jun NH2 terminal kinase phosphorylation in the absence of adiponectin. Adiponectin blocked palmitate- and thapsigargin-induced activation of c-Jun NH2 terminal kinase and reduced apoptosis. These data suggest that adiponectin is an important determinant of saturated fatty acid-induced apoptosis in liver cells and may have implications for fatty acid-mediated liver cell injury in adiponectin-deficient individuals.

Original languageEnglish
Pages (from-to)2278-2284
Number of pages7
JournalFEBS Journal
Volume276
Issue number8
DOIs
Publication statusPublished - 2009 Apr

Keywords

  • AMPK
  • Adiponectin
  • Apoptosis
  • JNK
  • Palmitate

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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