Comparison of the effects on lipid metabolism of dietary methionine and cystine between hepatoma-bearing and normal rats.

The effects of dietary supplementation with methionine and cystine on lipid metabolism, including the serum lipid concentration, were studied in Donryu rats subcutaneously implanted with an ascites hepatoma cell line (AH109A) for comparison with normal rats. A diet supplemented with 1.2% L-methionine or L-cystine to 20% casein was found to suppress the hepatoma-induced increases in serum triglyceride and total cholesterol concentration. The lipoprotein lipase activity in tissues was enhanced by dietary methionine and cystine, with no change in the mRNA level. Dietary methionine and cystine increased bile acid excretion into the feces with enhanced hepatic cholesterol 7alpha-hydroxylase activity. Dietary methionine and cystine affected the lipid metabolism differently in normal rats from hepatoma-bearing rats. These results suggest that dietary methionine and cystine each had a hypolipidemic effect against cancer-induced hyperlipidemia, and that the different actions observed in the hepatoma-bearing and normal rats may have been due to a metabolic abnormality caused by the cancer.

Serum lipid levels correlate with solid tumor weight in hepatoma-bearing rats fed dietary fish oil.

The effects of dietary fish oil (FO) on serum lipid levels and tumor proliferation were studied in Donryu rats subcutaneously implanted with the ascites hepatoma cell line AH109A. Solid tumor weight was significantly less and serum total cholesterol (T-Ch) level significantly lower in the groups fed the FO diet both before and after AH109A implantation than in the groups fed the corn oil diet. There were no significant effects in the serum lipid levels and tumor proliferation in the groups fed the FO diet only before or after the hepatoma implantation. The serum triacylglyceride, phospholipid, nonesterified fatty acid, T-Ch, and very-low-density lipoprotein+low-density lipoprotein-Ch levels showed significant positive correlations with the solid tumor weight. These results suggest that dietary FO ingestion after hepatoma implantation suppresses tumor proliferation and reduces serum lipid levels along with suppressing tumor proliferation.

Effects of simultaneous dietary fish oil ingestion and sulfur amino acid supplementation on the lipid metabolism in hepatoma-bearing rats with hyperlipidemia.

The effects of simultaneous dietary fish oil ingestion and sulfur amino acid (L-methionine and L-cystine) supplementation on serum lipid concentrations and various parameters related to the lipid metabolism were studied in Donryu rats subcutaneously implanted with an ascites hepatoma cell line, AH109A. A diet containing 10% fish oil was found to reduce serum triglyceride, total cholesterol, (very-low-density lipoprotein plus low-density lipoprotein)-cholesterol, phospholipid and nonesterified fatty acid (NEFA) concentrations in these animals, and dietary supplementation of 1.2% L-methionine and L-cystine also suppressed these serum lipid concentrations. Hepatic fatty acid synthesis and the availability of serum NEFA were decreased, and epididymal adipose tissue lipoprotein lipase (LPL) activity was elevated by dietary fish oil, while LPL activity in various tissues and hepatic fatty acid oxidation were increased by dietary sulfur amino acids, resulting in a reduction in the serum triglyceride concentration by dietary fish oil and sulfur amino acids, respectively. Dietary fish oil suppressed the hepatoma-induced increase in cholesterogenesis in the host liver, and dietary methionine and cystine enhanced bile acid excretion into feces, which were the causes of the hypocholesterolemic effect. In these serum lipid concentrations, there were significant effects of fish oil ingestion and sulfur amino acid supplementation, but no significant interaction between these two factors was seen. These results indicate that dietary fish oil and sulfur amino acid, L-methionine and L-cystine, have hypolipidemic effects in cancer-related hyperlipidemia, and that the effects of these two factors on the decrease in these serum lipid concentrations are additive; these two factors may affect the lipid metabolism via different pathways and mechanisms.

Possible involvement of phospholipase C and protein kinase C in stimulatory actions of L-leucine and its keto acid, alpha-ketoisocaproic acid, on protein synthesis in RLC-16 hepatocytes.

Effects of leucine and related compounds on protein synthesis were studied in RLC-16 hepatocytes. The incorporation of [(3)H] tyrosine into cellular protein was measured as an indexof protein synthesis. In leucine-depleted RLC-16 cells, L-leucineand its keto acid, alpha-ketoisocaproic acid (KIC), stimulated protein synthesis, while D-leucine did not. Mepacrine, an inhibitor of both phospholipase A(2) and C canceled stimulatory actions of L-leucine and KIC on protein synthesis, suggesting a possible involvement of either arachidonic acid metabolism by phospholipase A(2), cyclooxygenase or lipoxygenase, or phosphatidylinositol degradation by phospholipase C in the stimulatory actions of L-leucine and KIC.Neither indomethacin, an inhibitor of cyclooxygenase, nor caffeic acid, an inhibitor of lipoxygenase, diminished their stimulatory actions, suggesting no involvement of arachidonic acid metabolism. Conversely, 1-O-hexadecyl-2-O-methylglycerol, an inhibitor of protein kinase C, significantly canceled the stimulatory actions of L-leucine and KIC on protein synthesis, suggesting an involvement of phosphatidylinositol degradation and activation of protein kinase C. These results strongly suggest that both L-leucine and KIC stimulate protein synthesis in RLC-16 cells via activation of phospholipase C and production of diacylglycerol and inositol triphosphate from phosphatidylinositol, which in turn activate protein kinase C.

Comparison of the changes in lipid metabolism between hepatoma-bearing and lipopolysaccharide-treated rats.

To elucidate the mechanism for hyperlipidemia in the hepatoma-bearing state, changes in some parameters related to the lipid metabolism and serum tumor necrosis factor-alpha (TNF-alpha) level were examined in Donryu rats that had been subcutaneously implanted with an ascites hepatoma cell line of AH109A. These parameters were also examined in rats that had been given a single injection of lipopolysaccharide (LPS), a model for acute infection with TNF-alpha secretion into the blood circulation. The serum triglyceride and total cholesterol (Ch) levels were significantly higher in both the hepatoma-implanted and LPS-injected rats than in normal rats. The level of adipose tissue lipoprotein lipase was decreased by hepatoma implantation and LPS injection, while the hormone-sensitive lipase activity was increased by the same treatments. Fatty acid (FA) oxidation and Ch synthesis were also stimulated by both treatments. The serum TNF-alpha level was noticably elevated by hepatoma implantation and greatly by the LPS injection. This LPS injection increased hepatic FA synthesis. The serum high-density lipoprotein Ch level and hepatic Ch 7alpha-hydroxylase activity were not changed by the LPS injection. Hepatoma implantation led to hyperlipidemia and elevated the serum TNF-alpha level, as did the LPS injection.

Possible involvement of phospholipase A(2) and cyclooxygenase in stimulatory action of L-histidine on protein synthesis in L6 myotubes.

Effects of L-histidine and related compounds on protein synthesiswere studied in cultured L6 myotubes. L-Histidine specifically stimulated protein synthesis, whereas D-histidine, histamine, L-arginine and L-lysine did not. Inhibitors of phospholipase A(2), phospholipase C and cyclooxygenase intercepted the stimulatory action of L-histidine on protein synthesis, while inhibitors of protein kinase C and 5-lipoxygenase did not. These results suggest an involvement of phospholipase A(2) and cyclooxygenase in the stimulatory action of L-histidine on protein synthesis in L6 myotubes.

Involvement of protein kinase C activation in L-leucine-induced stimulation of protein synthesis in l6 myotubes.

Effects of leucine and related compounds on protein synthesis were studied in L6 myotubes. The incorporation of [(3)H]tyrosine into cellular protein was measured as an index of protein synthesis. In leucine-depleted L6 myotubes, leucine and its keto acid, alpha-ketoisocaproic acid (KIC), stimulated protein synthesis, while D-leucine did not. Mepacrine, an inhibitor of both phospholipases A(2) and C, canceled stimulatory actions of L-leucine and KIC on protein synthesis. Neither indomethacin, an inhibitor of cyclooxygenase, nor caffeic acid, an inhibitor of lipoxygenase, diminished their stimulatory actions, suggesting no involvement of arachidonic acid metabolism. Conversely, 1-O-hexadecyl-2-O-methylglycerol, an inhibitor of proteinkinase C, significantly canceled the stimulatory actions of L-leucine and KIC on protein synthesis, suggesting an involvement of phosphatidylinositol degradation and activation of protein kinase C. L-Leucine caused a rapid activation of protein kinase C in both cytosol and membrane fractions of the cells. These results strongly suggest that both L-leucine and KIC stimulate protein synthesis in L6 myotubes through activation of phospholipase C and protein kinase C.