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Full‐length adiponectin protects hepatocytes from palmitate‐induced apoptosis via inhibition of c‐Jun NH 2 terminal kinase
Author(s) -
Jung Tae Woo,
Lee Yong J.,
Lee Myung W.,
Kim Seon M.,
Jung Tae Woo
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.06955.x
Subject(s) - thapsigargin , adiponectin , apoptosis , endocrinology , medicine , protein kinase a , biology , kinase , chemistry , biochemistry , insulin , insulin resistance , intracellular
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 NH 2 terminal kinase phosphorylation in the absence of adiponectin. Adiponectin blocked palmitate‐ and thapsigargin‐induced activation of c‐Jun NH 2 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.