出版社：American Society for Biochemistry and Molecular Biology
摘要：Fatty acid oxidation provides energy in tissues with high metabolicdemands. During the acute-phase response (APR) induced by infectionand inflammation, fatty acid oxidation is decreased associatedwith hypertriglyceridemia. Little is known about the mechanismby which the APR decreases fatty acid oxidation. Therefore,we investigated whether the APR affects the expression of medium-chainacyl-coenzyme A dehydrogenase (MCAD), its regulator the estrogen-relatedreceptor (ERR), and a key coactivator of ERR, the peroxisomeproliferator-activated receptor coactivator-1 (PGC-1). mRNAlevels of PGC-1, ERR, and MCAD are markedly reduced in the liver,heart, and kidney of mice during the lipopolysaccharide (LPS)-inducedAPR. The decreases were rapid and occurred at very low dosesof LPS. MCAD activity in liver was also reduced. Furthermore,binding of hepatic nuclear extracts to the ERR response elementfound in the promoter region of MCAD was significantly decreasedduring the APR, suggesting the decreased transcription of theMCAD gene. The binding activity was identified as ERR by supershiftwith antibody to ERR. Similar decreases in mRNA levels of thesegenes occur during zymosan- and turpentine-induced inflammation,indicating that suppression of the PGC-1, ERR, and MCAD pathwayis a general response during infection and inflammation.
Our study provides a potential mechanism by which the APR decreasesfatty acid oxidation.Supplementary key words peroxisome proliferator-activated receptor coactivator-1 • ß-oxidation • fatty acid oxidation
(ERR
coactivator-1
