Article

Mechanisms of Gene Regulation by Fatty Acids

Nutrition, Metabolism and Genomics Group, Wageningen University, the Netherlands.
Advances in Nutrition (Impact Factor: 4.9). 03/2012; 3(2):127-34. DOI: 10.3945/an.111.001602
Source: PubMed

ABSTRACT Consumption of specific dietary fatty acids has been shown to influence risk and progression of several chronic diseases, such as cardiovascular disease, obesity, cancer, and arthritis. In recent years, insights into the mechanisms underlying the biological effects of fatty acids have improved considerably and have provided the foundation for the emerging concept of fatty acid sensing, which can be interpreted as the property of fatty acids to influence biological processes by serving as signaling molecules. An important mechanism of fatty acid sensing is via stimulation or inhibition of DNA transcription. Here, we focus on fatty acid sensing via regulation of gene transcription and address the role of peroxisome proliferator-activated receptors, sterol regulatory element binding protein 1, Toll-like receptor 4, G protein-coupled receptors, and other putative mediators.

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    • "For instance, FASN could be involved in the control of FA synthesis and oxidation through a direct effect on the concentration of malonyl-CoA, which was shown to help control lipid metabolism through inhibition (allosteric ) of β-oxidation by carnitine palmitoyltransferase 1 (CPT1; Saggerson, 2008; Foster, 2012). In addition, FASN also helps generate ligands for transcription regulators, including peroxisome proliferator–activated receptors (PPAR; Chakravarthy et al., 2009, Georgiadi and Kersten, 2012), sterol-regulatory element binding protein 1 (SREBP1), hepatocyte nuclear factor 4a (HNF4α), NF-E2–related factor-2 (NRF2), and toll-like receptor 4 (TLR4; Georgiadi and Kersten, 2012), all of which are important for lipid metabolism regulation. Fatty acid synthase also may affect protein activity indirectly , e.g., endothelial nitric-oxide synthase, through palmitoylation (Wei et al., 2011). "
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    Journal of Dairy Science 02/2015; 98(5). DOI:10.3168/jds.2014-8202 · 2.55 Impact Factor
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    • ", 2011 ) . As such , we chose to examine PPARα , anoth - er key regulator in adipogenesis ( Georgiadi and Kersten , 2012 ) . The expression of all 3 genes was affected by diet ( P ≤ 0 . "
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    • "The high rate of de novo synthesis generates essential lipids that are critical for the formation of cell membrane and produces extra energy for cancer proliferation and progression [22] [25] [42]. In contrast to fatty acid synthesis being downregulated in most normal human tissues, precancerous lesion and cancer cells upregulate fatty acid synthesis resulting in the high expression of FASN independent of dietary fat and independent of hormonal regulation in breast cancer (Figure 1) [17] [43]. "
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