We examined the effect of dietary oils with different fatty acid compositions on the growth of visceral adipose tissue in rats. Rats were fed for 4 mo starting at weaning a basal diet containing (12 g/100 g diet) perilla oil rich in (n-3) polyunsaturated fatty acids (PUFA), safflower oil rich in (n-6) PUFA, olive oil rich in monounsaturated fatty acid, or beef tallow rich in saturated fatty acids. The amount of food consumed and body weight gain did not differ among the four dietary groups. The weight of the epididymal fat pad and the serum triglyceride concentration in perilla oil-fed rats were significantly lower (P < 0.05) than those of olive oil- and beef tallow-fed groups. The product of [(volume of individual adipocytes) x (number of adipocytes in epididymal fat pad)], which presumably represents total adipocyte volume in the fat pad, was significantly lower (P < 0.05) in perilla oil-fed rats than in beef tallow- and olive oil-fed groups. Expression of the late genes of adipocyte differentiation, peroxisome proliferator-activated receptor alpha, adipocyte P2 and adipsin, was significantly (P < 0. 05) down-regulated in epididymal fat tissue of rats that had been fed perilla oil rather than beef tallow or olive oil, whereas expression of the early gene, lipoprotein lipase, was not significantly affected. Greater levels (P < 0.05) of (n-3) PUFA in the membrane phospholipid fraction of the fat tissue were observed in perilla oil-fed rats than in the other dietary groups. These results suggest that perilla oil or (n-3) PUFA prevents excessive growth of adipose tissue in rats at least in part by suppressing the late phase of adipocyte differentiation.
The effect of high-dose alanine on survival and liver function in rats with acute liver failure caused by a lethal dose of D-galactosamine (D-gal) was studied. Greater than 90% of control animals died within 5 days after D-gal injection, but alanine significantly decreased mortality, even when treatment was started at 12 hours after D-gal injection. Alanyl-glutamine had a slight effect, but glucose produced no improvement. There was marked elevation of the plasma aspartate transaminase (AST) level, prolongation of the prothrombin time, and a decrease of the arterial ketone body ratio (AKBR) and hepatic adenosine triphosphate (ATP) content within 12 hours after D-gal injection. The AKBR decreased in parallel with the decrease of the hepatic ATP content. These parameters were significantly improved in alanine-treated rats at 48 hours after the induction of liver damage, which was just before control rats began to die. The hepatic ATP content was significantly greater in alanine-treated rats than in the other rats (including normal controls), but glucose pretreatment had no effect. It was also found that the liver labeling index of partially hepatectomized rats was significantly elevated by alanine administration at 3 hours before measurement. In conclusion, alanine is effective for the treatment of experimental acute liver failure, probably caused by promotion of ATP synthesis. Ala may be a good candidate for clinical application because of its preventive effect on hepatocyte necrosis and its promotive effect on liver regeneration.
Two metalloendopeptidases, designated as Streptomyces griseus metalloendopeptidases I and II (SGMPI and SGMPII), were isolated from a commercial Pronase P by a method including affinity chromatography on carbobenzoxy-L-alaninyl-triethylenetetraminyl-Sepharose (Z-Ala-T-Sepharose). The two enzymes differed from each other in behavior on ion-exchange chromatography but showed the same amino-terminal sequence at least up to the 20th residue. Their molecular weights were both estimated to be 37,000 by SDS-polyacrylamide gel electrophoresis. Elemental and amino acid composition analyses indicated that both of them contained about 1 g atom of zinc and one cystine residue per mol of protein. Cleavage specificities of the two enzymes toward synthetic peptide-substrates were very similar to those observed with thermolysin. EDTA, o-phenanthroline, and phosphoramidon strongly inhibited these enzymes, while typical serine-protease inhibitors and cysteine-protease inhibitors had no effect. The findings clearly indicate that SGMPI and SGMPII can be classified into the family of zinc-endopeptidases. It was unexpectedly found, however, that these metalloendopeptidases were strongly inhibited by protein serine-protease inhibitors produced by Streptomycetes, such as Streptomyces subtilisin inhibitor (SSI), alkaline protease inhibitor-2c' (API-2c'), and plasminostreptin (PS).
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