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Effects of mepanipyrim on lipid metabolism in rats.

Our preceding paper reported that mepanipyrim, a new fungicide, induced fatty liver in the rat. This study was undertaken to examine this phenomenon further on hepatic triglyceride (TG) synthesis, on liver and serum lipid concentrations, and on concentration of serum very-low-density lipoprotein (VLDL) in rats fed for 3 weeks on the drug at 4,000 ppm. Mepanipyrim decreased the incorporation of 14C-acetate into hepatic TG, total cholesterol (TC) and total lipids. In addition, mepanipyrim treatment induced a drastic increase in hepatic TG accompanying a decrease in serum TG. Esterified cholesterol (CE), phospholipid (PL) and non-esterified fatty acid (NEFA) also increased in the liver with a concomitant decrease in the serum. The decrease of serum VLDL by mepanipyrim was comparable to the decrease in serum TG. Because hepatic TG is secreted into the blood by forming VLDL, which consists of TG, TC, PL, and apoprotein, the decrease in serum TG would be mainly ascribable to that in serum VLDL. Mepanipyrim also decreased serum concentrations of low-density lipoprotein (LDL) and high-density lipoprotein (HDL), and the relative weights of the epididymal adipose tissue, indicating that a reduction in serum VLDL does not reflect acceleration of serum VLDL dissimulation. These results suggest that the fatty liver induced by mepanipyrim would be due to the inhibition of hepatic VLDL synthesis or its secretion into the blood.