A pathway approach to investigate the function and regulation of SREBPs

Daemen, Sabine; Kutmon, Martina; Evelo, Chris T.

doi:10.1007/s12263-013-0342-x

Cited by 53 publications

(48 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Downregulation of SREBF-1 during early lactation was also observed by Graber et al (2010) and is reflected by a reduced expression of ACC and FASN in the peripartal period (Gross et al, 2013). Sterol regulatory element-binding factor 1, in contrast to SREBF-2, is known to be stimulated by insulin, as both SREBF-1 and insulin have been shown to induce lipogenesis (Daemen et al, 2013). Furthermore, insulin upregulates HMGCR in vitro (Bhasker and Friedmann, 2008) and, in diabetic rats, insulin was able to restore the decreased HMGCR levels (Ness et al, 1994).…”

Section: Discussionmentioning

confidence: 95%

“…Sterol regulatory element-binding factors are synthesized as endoplasmic reticulum membrane proteins. In the case of low cholesterol levels, they migrate to the Golgi apparatus where they are cleaved and then released as nuclear SREBF able to activate target genes (Desvergne et al, 2006;Daemen et al, 2013). During this translocation, posttranscriptional modifications of SREBF take place that might affect their further effects besides the mRNA expression level.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cholesterol metabolism, transport, and hepatic regulation in dairy cows during transition and early lactation

Kessler

Gross

Bruckmaier

et al. 2014

Journal of Dairy Science

116

View full text Add to dashboard Cite

The transition from the nonlactating to the lactating state represents a critical period for dairy cow lipid metabolism because body reserves have to be mobilized to meet the increasing energy requirements for the initiation of milk production. The purpose of this study was to provide a comprehensive overview on cholesterol homeostasis in transition dairy cows by assessing in parallel plasma, milk, and hepatic tissue for key factors of cholesterol metabolism, transport, and regulation.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Cholesterol metabolism, transport, and hepatic regulation in dairy cows during transition and early lactation

Kessler

Gross

Bruckmaier

et al. 2014

Journal of Dairy Science

116

View full text Add to dashboard Cite

show abstract

“…ACC and FAS, the key enzymes for the synthesis of fatty acids in the liver, are regulated by nuclear transcription factor SREBP-1c [15]. Studies have shown that the hepatic expression of SREBP-1c and its target lipid synthesis regulation genes, FAS and ACC, increase several times both in patients with NAFLD and in animal models such as transgenic mice, ob/ob mice (leptin deficiency results in an insulin resistance and hyperinsulinemia), and high-fat diet-fed mice and rats, which leads to deposition of a large amount of TG [16–20].…”

Section: Discussionmentioning

confidence: 99%

Schisandra polysaccharide inhibits hepatic lipid accumulation by downregulating expression of SREBPs in NAFLD mice

et al. 2016

View full text Add to dashboard Cite

BackgroundHepatoprotective effects of Chinese herbal medicine Schisandra Chinensis (Schisandra) have been widely investigated. However, most studies were focused on its lignan extracts. We investigated the effects of Schisandra polysaccharide (SCP) in a mouse model of non-alcoholic fatty liver disease (NAFLD), and studied its effect on sterol regulatory element binding proteins (SREBPs) and the related genes.MethodsThe mouse model of NAFLD was established by feeding mice with a high-fat diet for 16 weeks. Effect of SCP-treatment (100 mg/kg, once daily for 12 weeks) on biochemical parameters and liver histopathology was assessed. Relative levels of sterol regulatory element-binding proteins (SREBPs) and their gene expressions were determined by quantitative real-time polymerase chain reaction and Western Blot.ResultsSCP significantly reduced the liver index by 12.0%. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol, alanine aminotransferase and aspartate aminotransferase were decreased by 31.3, 28.3, 42.8, 20.1 and 15.5%, respectively. Serum high-density lipoprotein cholesterol was increased by 26.9%. Further, SCP lowered hepatic TC and TG content by 27.0% and 28.3%, respectively, and alleviated fatty degeneration and necrosis of liver cells. A significant downregulation of mRNA and protein expressions of hepatic lipogenesis genes, SREBP-1c, fatty acid synthase and acetyl-CoA carboxylase, and the mRNA expression of liver X receptor α (LXRα) was observed in NAFLD mice treated with SCP. SCP also significantly reduced the hepatic expression of SREBP-2 and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR).ConclusionThese findings demonstrate the hepatoprotective effects of SCP in a mouse model of NAFLD; the effects may be mediated via downregulation of LXRα/SREBP-1c/FAS/ACC and SREBP-2/HMGCR signaling pathways in the liver.

show abstract

“…Especially, SREBP2 is ubiquitouslly expressed, and relatively selective activator of cholesterol synthesis, as opposed to fatty acid synthesis, and regulates HMG-CoA reductase and low-density lipoprotein receptor (LDLR) genes 9, 10 . Since low levels of cholesterol stimulates SREBPs, the crucial role of SREBPs on liver steatosis and hyperlipedemia has been reported 9, 11 .…”

mentioning

confidence: 99%

Atheroprone Flow Activation of the Sterol Regulatory Element Binding Protein 2 and Nod-Like Receptor Protein 3 Inflammasome Mediates Focal Atherosclerosis

Abe

Berk

2013

Circulation

View full text Add to dashboard Cite

Athero-prone flow promotes inflammation in endothelial cells, and this process is critical for pathogenesis of many chronic inflammatory conditions such as coronary and carotid artery atherosclerosis, as well as abdominal aortic aneurysm. Signal mediators activated by athero-prone (disturbed) flow that have been described include NF-κB and protein kinase C, which is very different from athero-protective (steady laminar) flow1. In this issue a publication from Shyy’s lab shows the critical role of sterol regulatory element binding protein 2 (SREBP2) on athero-prone flow-mediated NLRP3 inflammasome activation2. In particular, they showed that athero-prone flow induced both mature form of SREBP2 (SREBP2-N) and SREBP2 mRNA induction, which transcriptionally increase NADPH oxidase 2 (Nox2) and NLRP3 expression, thereby leading to IL-1β expression and endothelial inflammation (Figure 1). In this editorial, we will briefly review the NLRP3 inflammasome and SREBP activation system, which play a key role in modulating athero-prone flow-mediated EC inflammation. We will also discuss the following important questions for the future; the role of local NLRP3 and IL-1β expression, mechanisms for two different types of flow (athero-prone flow vs. athero-protective flow) on SREBP2 activation, and other NLRP3 activators including thioredoxin-interacting protein (TXNIP).

show abstract

A pathway approach to investigate the function and regulation of SREBPs

Cited by 53 publications

References 106 publications

Cholesterol metabolism, transport, and hepatic regulation in dairy cows during transition and early lactation

Cholesterol metabolism, transport, and hepatic regulation in dairy cows during transition and early lactation

Schisandra polysaccharide inhibits hepatic lipid accumulation by downregulating expression of SREBPs in NAFLD mice

Atheroprone Flow Activation of the Sterol Regulatory Element Binding Protein 2 and Nod-Like Receptor Protein 3 Inflammasome Mediates Focal Atherosclerosis

Contact Info

Product

Resources

About