Exposure to chlorpyrifos increases neutral lipid accumulation with accompanying increased de novo lipogenesis and decreased triglyceride secretion in McArdle-RH7777 hepatoma cells

Abstract

Hepatic steatosis is associated with hepatic insulin resistance as well as hypertriglyceridemia. Recent studies have determined exposure to organophosphate (OP) pesticides can cause dyslipidemia and hepatic steatosis. However, the mechanisms through which OPs induced hepatic steatosis are not completely understood. Therefore, the current study was designed to determine if direct exposure to an OP insecticide, chlorpyrifos (CPS), could promote hepatic steatosis and identify putative mechanisms of CPS-induced steatosis. To determine if CPS exposure increased intracellular lipid accumulation, McA-RH7777 cells were incubated with CPS for 48h then lipid accumulation was determined by Oil Red O staining. Exposure to CPS significantly increased neutral lipid accumulation in a concentration-dependent manner. This increase in Oil Red O staining appears to be due to increased intracellular triglyceride accumulation. In addition to increasing neutral lipid accumulation under normal growth conditions, exposure to CPS increased free fatty acid-induced intracellular neutral lipid accumulation. CPS induced increases in intracellular neutral lipid/triglyceride accumulation appear to be due to increased extracellular free fatty acid accumulation, increased de novo lipogenesis, and decreased fatty acidinduced triglyceride secretion. In summary, the present studies indicate exposure to CPS can have a direct effect on the hepatocyte to promote hepatic steatosis by increasing intracellular lipid/triglyceride accumulation through increased extracellular free fatty acid accumulation, increased hepatic de novo lipogenesis, and decreased triglyceride efflux.