PMID- 17224343 OWN - NLM STAT- MEDLINE DCOM- 20070226 LR - 20220317 IS - 0026-0495 (Print) IS - 1532-8600 (Electronic) IS - 0026-0495 (Linking) VI - 56 IP - 2 DP - 2007 Feb TI - Tumor necrosis factor and interleukin 1 decrease RXRalpha, PPARalpha, PPARgamma, LXRalpha, and the coactivators SRC-1, PGC-1alpha, and PGC-1beta in liver cells. PG - 267-79 AB - During the acute phase response, cytokines induce marked alterations in lipid metabolism including an increase in serum triglyceride levels and a decrease in hepatic fatty acid oxidation, in bile acid synthesis, and in high-density lipoprotein levels. Here we demonstrate that tumor necrosis factor (TNF) and interleukin 1 (IL-1), but not IL-6, decrease the expression of retinoid X receptor alpha (RXRalpha), peroxisome proliferator-activated receptor alpha (PPARalpha), PPARgamma, liver X receptor alpha (LXRalpha), and coactivators PPARgamma coactivator 1alpha (PGC-1alpha), PGC-1beta, and steroid receptor coactivator 1 (SRC-1) in Hep3B human hepatoma cells. In addition, treatment of mice with TNF and IL-1 also decreased RXRalpha, PPARalpha, PPARgamma, LXRalpha, and PGC-1alpha messenger RNA (mRNA) levels in the liver. These decreases were accompanied by reduced binding of nuclear extracts to RXR, PPAR, and LXR response elements and decreased luciferase activity driven by PPAR and LXR response elements. In addition, the mRNA levels of proteins regulated by PPARalpha (carnitine palmitoyltransferase 1alpha) and LXR (sterol regulatory element binding protein) were decreased in Hep3B cells treated with TNF or IL-1. Finally, using constructs of the LXRalpha promoter or the PGC-1alpha promoter linked to luciferase, we were able to demonstrate that a decrease in transcription contributes to the reduction in mRNA levels of nuclear hormone receptors and coactivators. Thus, our results suggest that decreased expression of nuclear hormone receptors RXRalpha, PPARalpha, PPARgamma, and LXRalpha, as well as coactivators PGC-1alpha, PGC-1beta, and SRC-1 may contribute to the cytokine-induced alterations in hepatic lipid metabolism during the acute phase response. FAU - Kim, Min Sun AU - Kim MS AD - Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA. FAU - Sweeney, Trevor R AU - Sweeney TR FAU - Shigenaga, Judy K AU - Shigenaga JK FAU - Chui, Lisa G AU - Chui LG FAU - Moser, Arthur AU - Moser A FAU - Grunfeld, Carl AU - Grunfeld C FAU - Feingold, Kenneth R AU - Feingold KR LA - eng GR - R01 HD029706/HD/NICHD NIH HHS/United States GR - R01 HD029706-07/HD/NICHD NIH HHS/United States GR - R01 HD29706/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Metabolism JT - Metabolism: clinical and experimental JID - 0375267 RN - 0 (DNA-Binding Proteins) RN - 0 (Interleukin-1) RN - 0 (Liver X Receptors) RN - 0 (NR1H3 protein, human) RN - 0 (Nr1h3 protein, mouse) RN - 0 (Orphan Nuclear Receptors) RN - 0 (PPAR alpha) RN - 0 (PPAR gamma) RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - 0 (Ppargc1a protein, mouse) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Retinoid X Receptor alpha) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - 0 (Tumor Necrosis Factors) RN - EC 2.3.1.48 (Histone Acetyltransferases) RN - EC 2.3.1.48 (NCOA1 protein, human) RN - EC 2.3.1.48 (Ncoa1 protein, mouse) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) SB - IM MH - Acute-Phase Reaction/metabolism MH - Animals MH - Blotting, Northern MH - Blotting, Western MH - Cell Nucleus/metabolism MH - DNA-Binding Proteins/metabolism MH - Hepatocytes/drug effects/metabolism MH - Histone Acetyltransferases/metabolism MH - Interleukin-1/*pharmacology MH - Liver/drug effects/*metabolism MH - Liver X Receptors MH - Mice MH - Mice, Inbred C57BL MH - Nuclear Receptor Coactivator 1 MH - Orphan Nuclear Receptors MH - PPAR alpha/metabolism MH - PPAR gamma/metabolism MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha MH - RNA, Messenger/biosynthesis/isolation & purification MH - Receptors, Cell Surface/*metabolism MH - Receptors, Cytoplasmic and Nuclear/metabolism MH - Retinoid X Receptor alpha/metabolism MH - Trans-Activators/metabolism MH - Transcription Factors/metabolism MH - Transfection MH - Tumor Necrosis Factors/*pharmacology PMC - PMC2700944 MID - NIHMS17410 EDAT- 2007/01/17 09:00 MHDA- 2007/02/27 09:00 PMCR- 2009/06/24 CRDT- 2007/01/17 09:00 PHST- 2006/03/20 00:00 [received] PHST- 2006/10/18 00:00 [accepted] PHST- 2007/01/17 09:00 [pubmed] PHST- 2007/02/27 09:00 [medline] PHST- 2007/01/17 09:00 [entrez] PHST- 2009/06/24 00:00 [pmc-release] AID - S0026-0495(06)00372-6 [pii] AID - 10.1016/j.metabol.2006.10.007 [doi] PST - ppublish SO - Metabolism. 2007 Feb;56(2):267-79. doi: 10.1016/j.metabol.2006.10.007.