Palmitate induces insulin resistance without significant intracellular triglyceride accumulation in HepG2 cells.
Previous studies showed that increased release of free fatty acids from adipocytes leads to insulin resistance and triglyceride (TG) accumulation in the liver, which may progress into hepatic steatohepatitis. We and other investigators have previously reported that palmitate induces endoplasmic reticulum stress-mediated toxicity in several tissues. This work investigated whether palmitate could induce insulin resistance and steatosis in HepG2 cells. We treated cells with either saturated fatty acid (palmitate) or unsaturated fatty acid (oleate), and observed that palmitate significantly activated c-jun N-terminal kinase and inactivated protein kinase B. Both 4-phenylbutyric acid and glycerol significantly activated protein kinase B, confirming the involvement of endoplasmic reticulum stress in palmitate-mediated insulin resistance. Oleate, but not palmitate, significantly induced intracellular TG deposition and activated sterol regulatory element binding protein-1. Instead, diacylglycerol level and protein kinase C epsilon activity were significantly increased by palmitate, suggesting the possible role of diacylglycerol in palmitate-mediated lipotoxicity. Therefore, the present study clearly showed that palmitate impairs insulin resistance, but does not induce significant TG accumulation in HepG2 cells.
Lee
Jin-young
JY
Department of Food and Nutrition, Seoul National University, Seoul, Korea.
Cho
Hyang-Ki
HK
Kwon
Young Hye
YH
D001391:Azo Compounds; D015153:Blotting, Western; D002460:Cell Line; D002855:Chromatography, Thin Layer; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D005234:Fatty Liver / Q000139:chemically induced / Q000473:pathology; D005470:Fluorometry; D006651:Histocytochemistry; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000737:chemistry / Q000302:isolation & purification; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D018832:Molecular Chaperones; D019301:Oleic Acid / Q000494:pharmacology; D010078:Oxazines; D010168:Palmitates / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism*
D001391:Azo Compounds; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D018832:Molecular Chaperones; D010078:Oxazines; D010168:Palmitates; D014280:Triglycerides; D019301:Oleic Acid; C011049:oil red O; C044808:nile red