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.