Induction of peroxisomal beta-oxidation by a microbial catabolite of cholic acid in rat liver and cultured rat hepatocytes.
The capability of (4R)-4-(2,3,4,6,6a beta,7,8,9,9a alpha,9b beta-decahydro-6a beta-methyl-3-oxo-1H-cyclopental[f]quinolin-7 beta-yl)valeric acid (DCQVA), a catabolite of cholic acid produced by enterobacteria, to induce peroxisome proliferation in vivo and in vitro was studied. Rats given 0.3% DCQVA in the diet for 2 weeks showed marked increases in peroxisomal beta-oxidation, mitochondrial 2,4-dienoyl-CoA reductase and microsomal laurate omega-oxidation activities in the liver compared with control rats given the diet without DCQVA. Cultured rat hepatocytes treated with DCQVA for 72 h also exhibited greatly enhanced beta-oxidation activity. The increased activity was concentration-dependent and the effective concentrations were comparable with those of clofibric acid that produced the same degree of induction in the assay. The results demonstrate that DCQVA is a potent peroxisome proliferator that occurs naturally in rat intestine.
Nishimaki-Mogami
T
T
National Institute of Hygienic Sciences, Tokyo, Japan.
Takahashi
A
A
Toyoda
K
K
Hayashi
Y
Y
D000818:Animals; D002478:Cells, Cultured; D019826:Cholic Acid; D002793:Cholic Acids / Q000378:metabolism*; D002995:Clofibric Acid / Q000494:pharmacology; D004790:Enzyme Induction; D005227:Fatty Acids / Q000378:metabolism*; D006529:Hepatomegaly / Q000139:chemically induced; D008099:Liver / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000201:enzymology*; D010084:Oxidation-Reduction; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013347:Subcellular Fractions / Q000201:enzymology; D014631:Valerates / Q000494:pharmacology*
D002793:Cholic Acids; D005227:Fatty Acids; D011804:Quinolines; D014631:Valerates; C083646:4-(decahydromethyl-3-oxo-1H-cyclopentaquinolinyl)valeric acid; D002995:Clofibric Acid; D019826:Cholic Acid