Pégorier Jean-Paul, Le May Cédric, Girard Jean
Département d'Endocrinologie, Institut Cochin, INSERM U567, CNRS UMR8104, IFR Alfred JOST, Faculté de Médecine Cochin-Port-Royal, 24 rue du Faubourg Saint Jacques, 75014 Paris, France.
J Nutr. 2004 Sep;134(9):2444S-2449S. doi: 10.1093/jn/134.9.2444S.
The last decade provided evidence that major (glucose, fatty acids, amino acids) or minor (iron, vitamin, etc.) dietary constituents regulated gene expression in an hormonal-independent manner. This review focuses on molecular mechanisms by which fatty acids control the expression genes encoding regulatory protein involved in their own metabolism. Nonesterified fatty acids or their CoA derivatives seem to be the main signals involved in the transcriptional effect of long-chain fatty acids. The effects of fatty acids are mediated either directly owing to their specific binding to various nuclear receptors (PPAR, LXR, HNF-4alpha) leading to changes in the trans-activating activity of these transcription factors, or indirectly as the result of changes in the abundance of regulatory transcription factors (SREBP-1c, ChREBP, etc.). The relative contribution of each transcription factor in fatty acid-induced positive or negative gene expression is discussed.
过去十年的证据表明,主要(葡萄糖、脂肪酸、氨基酸)或次要(铁、维生素等)膳食成分以激素非依赖方式调节基因表达。本综述聚焦于脂肪酸控制参与其自身代谢的调节蛋白编码基因表达的分子机制。非酯化脂肪酸或其辅酶A衍生物似乎是长链脂肪酸转录效应的主要信号。脂肪酸的作用要么是由于它们与各种核受体(PPAR、LXR、HNF-4α)的特异性结合直接介导,导致这些转录因子的反式激活活性发生变化,要么是作为调节转录因子(SREBP-1c、ChREBP等)丰度变化的结果间接介导。讨论了每种转录因子在脂肪酸诱导的正性或负性基因表达中的相对贡献。