Cadoudal Thomas, Leroyer Stéphanie, Reis André F, Tordjman Joan, Durant Sylvie, Fouque Françoise, Collinet Martine, Quette Joelle, Chauvet Geneviève, Beale Elmus, Velho Gilberto, Antoine Bénédicte, Benelli Chantal, Forest Claude
Inserm UMR-S 530; Université Paris5, Centre Universitaire, U.F.R. Biomédicale, 45, rue des Saints-Pères, 75006 Paris, France.
Biochimie. 2005 Jan;87(1):27-32. doi: 10.1016/j.biochi.2004.12.005.
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.
血浆非酯化脂肪酸（NEFA）浓度升高现已被认为是胰岛素抵抗和2型糖尿病发病的关键因素。在禁食期间，循环中的NEFA来源于白色脂肪组织（WAT）中储存的三酰甘油的脂解作用。然而，这些脂肪酸中有很大一部分（30 - 70%）在脂肪细胞内重新酯化，从而发生循环利用，净脂肪酸输出远小于真正的脂解作用。实际上，脂解和脂肪酸重新酯化这两个拮抗过程之间的平衡控制着WAT中净脂肪酸释放的速率。在禁食期间，重新酯化需要甘油生成，即从丙酮酸、乳酸或某些氨基酸从头合成3 - 磷酸甘油。这个过程中的关键酶是磷酸烯醇式丙酮酸羧激酶的胞质同工型（PEPCK - C；EC 4.1.1.32）。最近的进展强调了甘油生成和PEPCK - C在WAT脂肪酸释放中的作用。结果表明，甘油生成确实对脂质稳态很重要，并且该途径的失调可能具有深远的病理生理影响。本综述重点关注脂肪酸、视黄酸、糖皮质激素和降血脂药物噻唑烷二酮类对甘油生成以及PEPCK - C基因表达和活性的调节。
