Differential effects of dietary fatty acids on rat liver alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase activity and gene expression.
Hepatic alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD; formerly termed picolinic carboxylase) [EC4.1.1.45] plays a key role in regulating NAD biosynthesis and the generation of quinolinate (quinolinic acid) from tryptophan. Quinolinate is a potent endogenous excitotoxin of neuronal cells. We previously reported that ingestion of fatty acids by rats leads to a decrease in their hepatic ACMSD activity. However, the mechanism of this phenomenon is not clarified. We previously purified ACMSD and cloned cDNA encoding rat ACMSD. Therefore, in this study, we examined the differential effect of fatty acids on ACMSD mRNA expression by Northern blot. Moreover, we measured quinolinic acid concentration in rats fed on fatty acid. When diets containing 2% level of fatty acid were given to male Sprague-Dawley rats (4 weeks old) for 8 days, long-chain saturated fatty acids and oleic acid did not affect ACMSD mRNA expression in the liver. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) strongly suppressed the liver ACMSD mRNA expression. In rats fed with high linoleic acid diet for 8 days, serum quinolinic acid was significantly increased as compared with the rats fed on a fatty acid-free diet under the condition of the approximately same calorie ingestion. These results suggest that the transcription level of ACMSD is modulated by polyunsaturated fatty acids, and suppressive potency of ACMSD mRNA is n-3 fatty acid family>linoleic acid (n-6 fatty acid)>saturated fatty acid. Moreover, this study provides the information that a high polyunsaturated fatty acid diet affects the production of quinolinic acid in serum by suppressing the ACMSD activity.
Egashira
Yukari
Y
Graduate School of Science and Technology, Chiba University, 648 Matsudo, Chiba 271 8510, Japan. egashira@faculty.chiba-u.jp
Murotani
Gen
G
Tanabe
Atsushi
A
Saito
Kuniaki
K
Uehara
Koich
K
Morise
Akiko
A
Sato
Mayuki
M
Sanada
Hiroo
H
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002262:Carboxy-Lyases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D002149:Energy Intake; D015870:Gene Expression / Q000187:drug effects; D019787:Linoleic Acid / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D017378:Quinolinic Acid / Q000097:blood; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013229:Stearic Acids / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism
D004041:Dietary Fats; D012333:RNA, Messenger; D013229:Stearic Acids; D014364:Tryptophan; D019787:Linoleic Acid; D002262:Carboxy-Lyases; C024396:aminocarboxymuconate-semialdehyde decarboxylase; D017378:Quinolinic Acid