Effects of tiadenol and Di-(2-ethylhexyl)phthalate on the metabolism of phosphatidylcholine and phosphatidylethanolamine in the liver of rats

Regulation of Phosphatidylethanolamine Homeostasis — The Critical Role of CTP:Phosphoethanolamine Cytidylyltransferase (Pcyt2)

“…Peroxisome proliferators (PP) modulate phospholipid levels in cancer and chronic administration of PP could increase the content of hepatic PC and PE for hepatomegaly and proliferation and cause liver cancer in rodents [36–38]. While the activity of Pcyt1 was decreased, the activity of Pcyt2 was unchanged during hepatomegaly, implying that the elevated PE was not synthesized de novo via the Kennedy pathway [37]. Suppression of the PE methyltransferase (PEMT) activity together with the increase in the PSD activity indicated that under the influence of PP additional liver PE was produced in mitochondria by the decarboxylation of PS (Figure 1) [37,38].…”

“…While the activity of Pcyt1 was decreased, the activity of Pcyt2 was unchanged during hepatomegaly, implying that the elevated PE was not synthesized de novo via the Kennedy pathway [37]. Suppression of the PE methyltransferase (PEMT) activity together with the increase in the PSD activity indicated that under the influence of PP additional liver PE was produced in mitochondria by the decarboxylation of PS (Figure 1) [37,38]. It was also reported that hexadecylphosphocholine (HePC), a lysophospholipid analogue of PC, decreased the cell growth in the liver hepatoma cells by inhibiting the activity of Pcyt1 and consequently decreasing the production of PC via the CDP-choline pathway [39].…”

Induction of Triglyceride Accumulation in the Liver of Rats by Perfluorinated Fatty Acids with Different Carbon Chain Lengths: Comparison with Induction of Peroxisomal .BETA.-Oxidation.

“…Peroxisome proliferators are known to induce peroxisomal b-oxidation in the liver of rodents including rats and, in general, to reduce the hepatic content of TG. 24) These findings suggest that the peroxisomal b-oxidation system induced by peroxisome proliferators functions to lower the hepatic level of TG by enhancing the degradation of fatty acids. The present study showed, however, that C9 and C10 induced peroxisomal b-oxidation and enhanced the accumulation of TG in the liver.…”

Triglyceride Accumulation by Peroxisome Proliferators in Rat Hepatocytes

“…The relationship between TG fluctuation and peroxisomal induction, including the peroxisome proliferation, the induction of several proteins, and increase in enzyme activities by PxPs, has not been fully elucidated, though an increase in Pxox activity and a reduction in hepatic TG level, 9,22) or contrarily, the activity and hepatic TG accumulation 11,18,19) in vivo have been reported. Two mechanisms of Px induction 32) have been proposed: 1) the receptor mediated theory, termed PPARs by Isseman et al, 4) which does not rule out the possibility that PxPs interact indirectly with the receptor, and 2) substrate overload, termed lipid pertubation, which is caused by a high cellular level of long acyl CoA 20) and PxP metabolites, the corresponding CoA thioesters.…”

“…A linear increasing correlation between Px-ox activity and cellular long chain fatty acid level by PxP was reported in rat cultured hepatocytes, 16) leading to hepatic TG accumulation when the TG synthesis process was completed, as well as a fibrate and a long chain fatty acid enhanced cellular TG level with a increase in Px-ox activity. 17) In in vivo experiments, PxPs including fatty acid analogues enhanced hepatic TG accumulation, 11,18,19) or in contrast, decrease it, [20][21][22] when the increase in Px-ox activity and the decrease in plasma TG were simultaneously observed. These discrepancy results could be due to the fact that physiological lipid metabolism is regulated by complicated, precise, and divers endogenous factors.…”