SREBP-1c Transcription Factor and Lipid Homeostasis: Clinical Perspective

Ferré, Pascal; Foufelle, Fabienne

doi:10.1159/000100426

Cited by 292 publications

(262 citation statements)

References 177 publications

(122 reference statements)

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“…Since the mRNA levels of the above lipogenic enzymes are known to be regulated by SREBP-1c [6,20], its expression was evaluated next. The mRNA levels of SREBP-1c were positively correlated with those of FAS (r = 0.570, P < 0.001), ACC1 (r = 0.572, P < 0.001), and DGAT1 (r = 0.516, P < 0.001).…”

Section: Decreased Srebp-1c Mrna Levels In Advanced Nashmentioning

confidence: 99%

“…The activity of SREBP-1c is influenced by several post-transcriptional modification steps, i.e., processing of precursor SREBP-1c proteins (maturation) and translocation of mature SREBP-1c proteins into the nucleus [6,20]. To confirm whether mature SREBP-1c levels were also reduced in advanced NASH, immunoblot analysis was performed.…”

Section: Decreased Mature Srebp-1c Levels In Advanced Nashmentioning

confidence: 99%

“…It is reported that LXR, RXR, insulin, and pro-inflammatory cytokines, such as TNF- and IL-1, can modulate the mRNA levels of SREBP-1c [20,30].…”

Section: It Is Conceivable That the Down-regulation Of Srebp-1c In Admentioning

confidence: 99%

See 2 more Smart Citations

Down-regulation of SREBP-1c is associated with the development of burned-out NASH

Nagaya

Tanaka

Suzuki

et al. 2010

Journal of Hepatology

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Section: Decreased Srebp-1c Mrna Levels In Advanced Nashmentioning

confidence: 99%

Section: Decreased Mature Srebp-1c Levels In Advanced Nashmentioning

confidence: 99%

See 1 more Smart Citation

Down-regulation of SREBP-1c is associated with the development of burned-out NASH

Nagaya

Tanaka

Suzuki

et al. 2010

Journal of Hepatology

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“…SREBP-1C is a nuclear transcription factor, also known as an adipocyte determination and differentiation factor. It is involved in regulation of the fatty acids, TG synthesis-related enzymes, and fat synthesis by regulating the transcription of genes-encoding key enzymes-in adipogenesis [15]. Adipogenesis was found to be increased in transgenic mice with SREBP-1C gene over-expression.…”

Section: Introductionmentioning

confidence: 99%

Effects of nuclear receptor FXR on the regulation of liver lipid metabolism in patients with non-alcoholic fatty liver disease

2010

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Objective The aim of this study was to explore the role of farnesoid X receptor (FXR) in liver lipid metabolism of non-alcoholic fatty liver disease (NAFLD) patients. Methods In this study, pathology and clinical criteria confirmed NAFLD in patients. Fatty acid synthetase (FAS)-positive liver cells were visualized by laser scanning confocal microscopy. Levels of FXR, liver X receptor (LXR), sterol regulatory element binding protein 1C (SREBP-1C), and small heterodimer partner (SHP) proteins were detected by Western blot. FXR, LXR, and SHP mRNA levels were measured by real-time PCR. Results In patients with NAFLD, a significant positive relationship between the degree of hepatic steatosis and serum triglycerides and cholesterol (correlation coefficient [ 0.5, P \ 0.05) was seen. The NAFLD patients had more FAS protein in liver, which suggests that there could have been more of fatty acid synthesis in hepatic cells (P \ 0.05). The levels of FXR protein and mRNA were decreased in patients with NAFLD (P \ 0.05), while those of LXR and SREBP-1C were increased (P \ 0.05). The levels of SREBP-1C positively correlated with the degree of hepatic steatosis. There were no differences between the levels of SHP protein and mRNA both in NAFLD patients and normal controls (P [ 0.05).Conclusion Our data showed that the decreased expression of hepatic FXR is associated with an increased expression of LXR, SREBP-1C, and hepatic triglyceride synthesis; furthermore, increased SREBP-1C is associated with the degree of hepatic steatosis in the NAFLD patients.

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“…A major function of SREBP-1c is to activate genes involved in the synthesis of fatty acid and their incorporation into triglycerides and phospholipids (Horton et al, 2002;Eberle et al, 2004). As such, abnormal higher levels of SREBP-1c will result in lipid accumulation in the liver and cause steatosis (Ferre & Foufelle, 2007). Fatty acid synthase (FAS) is a well established target gene of SREBP-1c (Latasa et al, 2000;Amemiya-Kudo et al, 2002).…”

mentioning

confidence: 99%

Activation of sterol regulatory element-binding protein 1c and fatty acid synthase transcription by hepatitis C virus non-structural protein 2

Oem

Jackel‐Cram

et al. 2008

Journal of General Virology

106

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Transcriptional factor sterol regulatory element-binding protein 1c activates the transcription of lipogenic genes, including fatty acid synthase (FAS). Hepatitis C virus (HCV) infection is often associated with lipid accumulation within the liver, known as steatosis in the clinic. The molecular mechanisms of HCV-associated steatosis are not well characterized. Here, we showed that HCV non-structural protein 2 (NS2) activated SREBP-1c transcription in human hepatic Huh-7 cells as measured by using a human SREBP-1c promoter-luciferase reporter plasmid. We further showed that sterol regulatory element (SRE) and liver X receptor element (LXRE) in the SREBP-1c promoter were involved in SREBP-1c activation by HCV NS2. Furthermore, expression of HCV NS2 resulted in the upregulation of FAS transcription. We also showed that FAS upregulation by HCV NS2 was SREBP-1-dependent since deleting the SRE sequence in a FAS promoter and expressing a dominant-negative SREBP-1 abrogated FAS promoter upregulation by HCV NS2. Taken together, our results suggest that HCV NS2 can upregulate the transcription of SREBP-1c and FAS, and thus is probably a contributing factor for HCV-associated steatosis.Sterol regulatory element-binding protein 1c (SREBP-1c) is a member of the basic helix-loop-helix leucine zipper family of transcription factors (Horton et al., 2002;Eberle et al., 2004). SREBP-1c expression is regulated at the transcription level (Desvergne et al., 2006). For instance, liver X receptor (LXR) activates SREBP-1c transcription by binding to the LXR element (LXRE) sequences in the SREBP-1c promoter (Yoshikawa et al., 2001;Tarling et al., 2004;Dif et al., 2006). SREBP-1c can also regulate its own transcription in a positive feed-back loop through binding to the sterol regulatory elements (SREs) in the SREBP-1c promoter (Amemiya-Kudo et al., 2000). The newly synthesized, precursor SREBP-1c protein is bound to the endoplasmic reticulum (ER). Following proteolytic digestions, the amino-terminal domain is released and transported to the nucleus as an active transcriptional factor (Brown et al., 2000). The processed, mature SREBP-1 proteins are modified by phosphorylation by protein kinases, such as mitogen-activated protein kinase (MAPK), protein kinase A (PKA) and glycogen synthase kinase-3b (Kotzka et al., 1998;Roth et al., 2000;Lu & Shyy, 2006;Punga et al., 2006). The impact of phosphorylation on the transcriptional activity of SREBP-1 is less clear. For instance, phosphorylation by MAPK appears to enhance the transcriptional activity of SREBP-1, whereas PKA phosphorylation suppresses the function of SREBP-1 (Kotzka et al., 1998Lu & Shyy, 2006). A major function of SREBP-1c is to activate genes involved in the synthesis of fatty acid and their incorporation into triglycerides and phospholipids (Horton et al., 2002;Eberle et al., 2004). As such, abnormal higher levels of SREBP-1c will result in lipid accumulation in the liver and cause steatosis (Ferre & Foufelle, 2007). Fatty acid synthase (FAS) is a well established target gen...

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SREBP-1c Transcription Factor and Lipid Homeostasis: Clinical Perspective

Cited by 292 publications

References 177 publications

Down-regulation of SREBP-1c is associated with the development of burned-out NASH

Down-regulation of SREBP-1c is associated with the development of burned-out NASH

Effects of nuclear receptor FXR on the regulation of liver lipid metabolism in patients with non-alcoholic fatty liver disease

Activation of sterol regulatory element-binding protein 1c and fatty acid synthase transcription by hepatitis C virus non-structural protein 2

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