title: Inflammation inhibits the expression of phosphoenolpyruvate carboxykinase in liver and adipose tissue.
abstract: Inhibition of adipocyte triglyceride biosynthesis is required for fatty acid mobilization during inflammation. Triglyceride biosynthesis requires glycerol 3-phosphate and phosphoenolpyruvate carboxykinase (PEPCK) plays a key role. We demonstrate that LPS, zymosan, and TNF-α decrease PEPCK in liver and fat. Turpentine decreases PEPCK in liver, but not in fat. The LPS-induced decrease in PEPCK does not occur in TLR4 deficient animals, indicating that this receptor is required. The LPS-induced decrease in hepatic PEPCK does not occur in TNF receptor/IL-1 receptor knockout mice, but occurs in fat, indicating that TNF-α/IL-1 is essential for the decrease in liver but not fat. In 3T3-L1 adipocytes TNF-α, IL-1, IL-6, and IFNγ inhibit PEPCK indicating that there are multiple pathways by which PEPCK is decreased in adipocytes. The binding of PPARγ and RXRα to the PPARγ response element in the PEPCK promoter is markedly decreased in adipose tissue nuclear extracts from LPS treated animals. Lipopolysaccharide and zymosan reduce PPARγ and RXRα expression in fat, suggesting that a decrease in PPARγ and RXRα accounts for the decrease in PEPCK. Thus, there are multiple cytokine pathways by which inflammation inhibits PEPCK expression in adipose tissue which could contribute to the increased mobilization of fatty acids during inflammation.
authors: Metabolism Section, Department of Veterans Affairs Medical Center, University of California San Francisco, San Francisco, CA, USA. kenneth.feingold@ucsf.edu
authors: Kenneth R
authors: KR
authors: Feingold
authors: Arthur
authors: A
authors: Moser
authors: Judy K
authors: JK
authors: Shigenaga
authors: Carl
authors: C
authors: Grunfeld
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000201:enzymology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D024202:Electrophoretic Mobility Shift Assay; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology*; D008066:Lipolysis / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047495:PPAR gamma / Q000378:metabolism; D010730:Phosphoenolpyruvate Carboxylase / Q000096:biosynthesis*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014425:Turpentine / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
chemical_list: D016207:Cytokines; D018076:DNA, Complementary; D005230:Fatty Acids, Nonesterified; D008070:Lipopolysaccharides; D047495:PPAR gamma; D047490:Retinoid X Receptor alpha; D051197:Toll-Like Receptor 4; D012313:RNA; D015054:Zymosan; D010730:Phosphoenolpyruvate Carboxylase; D014425:Turpentine