Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10804393 | Biochimie | 2005 | 6 Pages |
Abstract
Elevated concentration of plasma non-esterified fatty acids (NEFA) is now recognized as a key factor in the onset of insulin-resistance and type 2 diabetes mellitus. During fasting, circulating NEFAs arise from white adipose tissue (WAT) as a consequence of lipolysis from stored triacylglycerols. However, a significant part of these FAs (30-70%) is re-esterified within the adipocyte, so that a recycling occurs and net FA output is much less than « true » lipolysis. Indeed, a balance between two antagonistic processes, lipolysis and FA re-esterification, controls the rate of net FA release from WAT. During fasting, re-esterification requires glyceroneogenesis defined as the de novo synthesis of glycerol-3-P from pyruvate, lactate or certain amino acids. The key enzyme in this process is the cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK-C; EC 4.1.1.32). Recent advance has stressed the role of glyceroneogenesis and of PEPCK-C in FA release from WAT. Results indicate that glyceroneogenesis is indeed important to lipid homeostasis and that a disregulation in this pathway may have profound pathophysiological effects. The present review focuses on the regulation of glyceroneogenesis and of PEPCK-C gene expression and activity by FAs, retinoic acids, glucocorticoids and the hypolipidemic class of drugs, thiazolidinediones.
Keywords
TZDTAGPEPCK-CDR1RXRNEFAHbA1cRetinoid X receptorPEPCKPPARC/EBPPPREFatty acidnon-esterified fatty acidsAdipose tissueWhite adipose tissuetriacylglycerolThiazolidinedioneType 2 diabetesRexinoidPPAR response elementglycosylated hemoglobin A1cCCAAT enhancer binding proteinSingle nucleotide polymorphismSNPWATGlitazonePeroxisome proliferator activated receptor
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Authors
Thomas Cadoudal, Stéphanie Leroyer, André F. Reis, Joan Tordjman, Sylvie Durant, Françoise Fouque, Martine Collinet, Joelle Quette, Geneviève Chauvet, Elmus Beale, Gilberto Velho, Bénédicte Antoine, Chantal Benelli, Claude Forest,