Dietary fat and peroxisome-proliferators affect production of quinolinate in rats, accompanied with suppression of gene expression of α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD)

Hepatic α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) plays a key role in regulating NAD biosynthesis from tryptophan. ACMSD also seems to affect the generation of quinolinic acid (QA), a neurotoxin l-tryptophan metabolite. QA is also a potential endogenous toxin. The aim of this study was to evaluate QA concentration and ACMSD mRNA expression after dietary fat or peroxisome-proliferator ingestion. When male Sprague-Dawley rats were fed a clofibrate-free diet (control), or a clofibrate-containing diet for 8 days, hepatic ACMSD mRNA in rats consuming the clofibrate diet was strongly suppressed, as compared with that fed the control. Shifting from the control diet to a clofibrate diet suppressed ACMSD mRNA strongly at day 1 and continued through day 4. However, ACMSD activity decreased gradually. In rats fed with several kinds of peroxisome-proliferator-containing diets, the hepatic ACMSD mRNA was drastically decreased by all the peroxisome-proliferators we used. On the other hand, linoleic acid, clofibrate, bezafibrate and Wy-14,643 affected the serum QA levels. The change of serum QA concentration after peroxisome-proliferator ingestion is suggested to be, in part, due to a decreased ACMSD gene expression. These results suggest that the ingestion of peroxisome-proliferators affect serum QA concentration and that the transcription level of hepatic ACMSD is modulated by peroxisome-proliferators.