scholarly journals Glucose induces de novo lipogenesis in rat muscle satellite cells through a sterol-regulatory-element-binding-protein-1c-dependent pathway

2004 ◽  
Vol 117 (10) ◽  
pp. 1937-1944 ◽  
Author(s):  
I. Guillet-Deniau
Keyword(s):  
Satellite Cells ◽  
De Novo ◽  
Binding Protein ◽  
Regulatory Element ◽  
De Novo Lipogenesis ◽  
Muscle Satellite Cells ◽  
Rat Muscle ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Dependent Pathway

scholarly journals Sterol Regulatory Element Binding Protein Regulates the Expression and Metabolic Functions of Wild-Type and OncogenicIDH1

2016 ◽  
Vol 36 (18) ◽  
pp. 2384-2395 ◽  
Author(s):  
Stéphane J. H. Ricoult ◽  
Christian C. Dibble ◽  
John M. Asara ◽  
Brendan D. Manning
Keyword(s):  
Carbon Flux ◽  
De Novo ◽  
Binding Protein ◽  
Regulatory Element ◽  
Lipid Synthesis ◽  
Reducing Power ◽  
Isocitrate Dehydrogenase 1 ◽  
Metabolic Functions ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Sterol regulatory element binding protein (SREBP) is a major transcriptional regulator of the enzymes underlyingde novolipid synthesis. However, little is known about the SREBP-mediated control of processes that indirectly support lipogenesis, for instance, by supplying reducing power in the form of NAPDH or directing carbon flux into lipid precursors. Here, we characterize isocitrate dehydrogenase 1 (IDH1) as a transcriptional target of SREBP across a spectrum of cancer cell lines and human cancers. IDH1 promotes the synthesis of lipids specifically from glutamine-derived carbons. Neomorphic mutations in IDH1 occur frequently in certain cancers, leading to the production of the oncometabolite 2-hydroxyglutarate (2-HG). We found that SREBP induces the expression of oncogenic IDH1 and influences 2-HG production from glucose. Treatment of cells with 25-hydroxycholesterol or statins, which respectively inhibit or activate SREBP, further supports SREBP-mediated regulation of IDH1 and, in cells with oncogenic IDH1, carbon flux into 2-HG.

scholarly journals USP7 mediates pathological hepatic de novo lipogenesis through promoting stabilization and transcription of ZNF638

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Wenkai Ni ◽  
Shengli Lin ◽  
Saiyan Bian ◽  
Wenjie Zheng ◽  
Lishuai Qu ◽  
...  
Keyword(s):  
Fatty Acid Synthase ◽  
Zinc Finger Protein ◽  
De Novo ◽  
Binding Protein ◽  
Regulatory Element ◽  
Liver Steatosis ◽  
Underlying Mechanism ◽  
De Novo Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
Element Binding Protein

Abstract Aberrant de novo lipogenesis (DNL) results in excessive hepatic lipid accumulation and liver steatosis, the causative factors of many liver diseases, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC). However, the underlying mechanism of DNL dysregulation remains largely unknown. Ubiquitination of proteins in hepatocytes has been shown to be widely involved in lipid metabolism of liver. Here, we revealed that Ubiquitin-specific peptidase 7 (USP7), a deubiquitinase (DUB), played key roles in DNL through regulation of zinc finger protein 638 (ZNF638) in hepatocytes. USP7 has been shown not only to interact with and deubiquitylate ZNF638, but also to facilitate the transcription of ZNF638 via the stabilization of cAMP responsive element binding protein (CREB). USP7/ZNF638 axis selectively increased the cleavage of sterol regulatory element binding protein (SREBP1C) through AKT/mTORC1/S6K signaling, and formed USP7/ZNF638/SREBP1C nuclear complex to regulate lipogenesis-associated enzymes, including acetyl-CoA carboxylase (ACACA), fatty acid synthase (FASN), and Stearoyl-CoA desaturase (SCD). In the mice liver steatosis model induced by fructose, USP7 or ZNF638 abrogation significantly ameliorated disease progression. Furthermore, USP7/ZNF638 axis participated in the progression of lipogenesis-associated HCC. Our results have uncovered a novel mechanism of hepatic DNL, which might be beneficial to the development of new therapeutic targets for hepatic lipogenesis-associated diseases.

scholarly journals Oleanolic Acid Diminishes Liquid Fructose-Induced Fatty Liver in Rats: Role of Modulation of Hepatic Sterol Regulatory Element-Binding Protein-1c-Mediated Expression of Genes Responsible for De Novo Fatty Acid Synthesis

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Changjin Liu ◽  
Ying Li ◽  
Guowei Zuo ◽  
Wenchun Xu ◽  
Huanqing Gao ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Target Genes ◽  
Nuclear Protein ◽  
De Novo ◽  
Binding Protein ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Oleanolic acid (OA), contained in more than 1620 plants and as an aglycone precursor for naturally occurred and synthesized triterpenoid saponins, is used in China for liver disorders in humans. However, the underlying liver-protecting mechanisms remain largely unknown. Here, we found that treatment of rats with OA (25 mg/kg/day, gavage, once daily) over 10 weeks diminished liquid fructose-induced excess hepatic triglyceride accumulation without effect on total energy intake. Attenuation of the increased vacuolization and Oil Red O staining area was evident on histological examination of liver in OA-treated rats. Hepatic gene expression profile demonstrated that OA suppressed fructose-stimulated overexpression of sterol regulatory element-binding protein-(SREBP-) 1/1c mRNA and nuclear protein. In accord, overexpression of SREBP-1c-responsive genes responsible for fatty acid synthesis was also downregulated. In contrast, overexpressed nuclear protein of carbohydrate response element-binding protein and its target genes liver pyruvate kinase and microsomal triglyceride transfer protein were not altered. Additionally, OA did not affect expression of peroxisome proliferator-activated receptor-gamma- and -alpha and their target genes. It is concluded that modulation of hepatic SREBP-1c-mediated expression of the genes responsible for de novo fatty acid synthesis plays a pivotal role in OA-elicited diminishment of fructose-induced fatty liver in rats.

scholarly journals 4β-hydroxycholesterol is a pro-lipogenic factor that promotes SREBP1c expression and activity through Liver X-receptor

2020 ◽  
Author(s):  
Ofer Moldavski ◽  
Peter-James H. Zushin ◽  
Charles A. Berdan ◽  
Robert J. Van Eijkeren ◽  
Xuntian Jiang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
De Novo ◽  
Regulatory Element ◽  
Liver X Receptor ◽  
De Novo Lipogenesis ◽  
Primary Hepatocytes ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Derivatives Of ◽  
Oxidized Derivatives Of Cholesterol

Oxysterols are oxidized derivatives of cholesterol that play signaling roles in lipid biosynthesis and homeostasis. Here we show that 4β-hydroxycholesterol (4β-HC), a liver and serum abundant oxysterol of poorly defined function, is a potent and selective inducer of the master lipogenic transcription factor, Sterol Regulatory Element Binding Protein 1c (SREBP1c), but not the related steroidogenic transcription factor SREBP2. Mechanistically, 4β-HC acts as a putative agonist for Liver X receptor (LXR), a sterol sensor and transcriptional regulator previously linked to SREBP1c activation. Unique among the oxysterol agonists of LXR, 4β-HC induced expression of the lipogenic program downstream of SREBP1c, and triggered de novo lipogenesis both in primary hepatocytes and in mouse liver. 4β-HC-acted in parallel to insulin-PI3K-dependent signaling to stimulate triglyceride synthesis and lipid droplet accumulation. Thus, 4β-HC is an endogenous regulator of de novo lipogenesis through the LXR-SREBP1c axis.

scholarly journals Hairpin Orientation of Sterol Regulatory Element-binding Protein-2 in Cell Membranes as Determined by Protease Protection

1995 ◽  
Vol 270 (49) ◽  
pp. 29422-29427 ◽  
Author(s):  
Xianxin Hua ◽  
Juro Sakai ◽  
Ho Y. K. ◽  
Joseph L. Goldstein ◽  
Michael S. Brown
Keyword(s):  
Cell Membranes ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element
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