scholarly journals Cross-Talk between Peroxisome Proliferator-Activated Receptor (PPAR) α and Liver X Receptor (LXR) in Nutritional Regulation of Fatty Acid Metabolism. I. PPARs Suppress Sterol Regulatory Element Binding Protein-1c Promoter through Inhibition of LXR Signaling

2003 ◽  
Vol 17 (7) ◽  
pp. 1240-1254 ◽  
Author(s):  
Tomohiro Yoshikawa ◽  
Tomohiro Ide ◽  
Hitoshi Shimano ◽  
Naoya Yahagi ◽  
Michiyo Amemiya-Kudo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Regulatory Element ◽  
Liver X Receptor ◽  
Peroxisome Proliferator ◽  
Nutritional Regulation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals Effects of fatty acids on gene expression: role of peroxisome proliferator-activated receptor α, liver X receptor α and sterol regulatory element-binding protein-1c

2002 ◽  
Vol 61 (3) ◽  
pp. 371-374 ◽  
Author(s):  
Sander Kersten
Keyword(s):  
Fatty Acids ◽  
Binding Protein ◽  
Regulatory Element ◽  
Liver X Receptor ◽  
Dietary Fatty Acids ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Liver X Receptor Α ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Dietary fatty acids have numerous effects on cellular function, many of which are achieved by altering the expression of genes. The present paper reviews recent data on the mechanisms by which fatty acids influence DNA transcription, and focus specifically on the importance of three transcription factors: peroxisome proliferator-activated receptor α; liver X receptor α; sterol regulatory element-binding protein 1c. These data indicate that fatty acids induce or inhibit the mRNA expression of a variety of different genes by acting both as agonists and as antagonists for nuclear hormone receptors.

scholarly journals Insulin induction of glucokinase and fatty acid synthase in hepatocytes: analysis of the roles of sterol-regulatory-element-binding protein-1c and liver X receptor

2006 ◽  
Vol 399 (2) ◽  
pp. 275-283 ◽  
Author(s):  
Franck Hansmannel ◽  
Sylvie Mordier ◽  
Patrick B. Iynedjian
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Glycogen Synthase ◽  
Binding Protein ◽  
Regulatory Element ◽  
Positive Control ◽  
Liver X Receptor ◽  
Transcription Activator ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

The transcription activator SREBP-1c (sterol-regulatory-element-binding protein-1c) is induced by insulin in the liver and is considered a master regulator of lipogenic genes such as FASN (fatty acid synthase). The question of whether SREBP-1c is also a mediator of insulin action on the regulatory enzyme of glucose metabolism GCK (glucokinase) is controversial. In the present paper, we induced SREBP-1c to various levels with insulin or the liver X receptor ligand T0901317 in primary hepatocytes and asked if these levels correlated with those of GCK or FASN mRNA expression, using the latter as positive control. Insulin and T0901317 triggered the accumulation of precursor and processed forms of SREBP-1c to similar levels and with comparable kinetics, and both effectors together caused synergistic increases in SREBP-1c protein levels. These effects were accompanied by commensurate elevation of FASN mRNA, notably by a synergistic response to both effectors. By contrast, GCK mRNA was unresponsive to T0901317 and was induced only by insulin. Treatment of hepatocytes with insulin and/or T0901317 resulted in the recruitment of SREBP-1c to the FASN promoter as shown by chromatin immunoprecipitation, whereas SREBP-1c did not bind to the GCK promoter. Lastly, we observed that the glycogen synthase kinase-3 inhibitor SB216763 produced a small increase in SREBP-1c protein level, which was further augmented in the presence of T0901317. The level of FASN mRNA varied in parallel with SREBP-1c, while GCK mRNA was unaffected. Collectively, these results showed that increases in SREBP-1c were neither necessary nor sufficient for GCK induction in hepatocytes, while at the same time they underscored the role of SREBP-1c as a key regulator of FASN.

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