Full-length adiponectin protects hepatocytes from palmitate-induced apoptosis via inhibition of c-Jun NH2 terminal kinase.
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 micromol L(-1) of albumin-bound oleate or palmitate for 24 h. The adiponectin concentrations used were: 0, 1, 10 or 100 microg 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.
Jung
Tae W
TW
Samsung Biomedical Institute, Seoul, Korea. ohayo2030@hanmail.net
Lee
Yong J
YJ
Lee
Myung W
MW
Kim
Seon M
SM
Jung
Tae W
TW
D052242:Adiponectin / Q000378:metabolism*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019301:Oleic Acid / Q000378:metabolism; D010168:Palmitates / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D019284:Thapsigargin / Q000494:pharmacology
D052242:Adiponectin; D010168:Palmitates; D019301:Oleic Acid; D019284:Thapsigargin; D019869:Phosphatidylinositol 3-Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3