scholarly journals Sterol Regulatory Element Binding Protein 1a Regulates Hepatic Fatty Acid Partitioning by Activating Acetyl Coenzyme A Carboxylase 2

2009 ◽  
Vol 29 (21) ◽  
pp. 5974-5974
Author(s):  
Seung-Soon Im ◽  
Linda E. Hammond ◽  
Leyla Yousef ◽  
Cherryl Nugas-Selby ◽  
Dong-Ju Shin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Coenzyme A ◽  
Binding Protein ◽  
Regulatory Element ◽  
Acetyl Coenzyme A ◽  
Hepatic Fatty Acid ◽  
Acetyl Coenzyme ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Acetyl Coenzyme A Carboxylase

scholarly journals Sterol Regulatory Element Binding Protein 1a Regulates Hepatic Fatty Acid Partitioning by Activating Acetyl Coenzyme A Carboxylase 2

2009 ◽  
Vol 29 (17) ◽  
pp. 4864-4872 ◽  
Author(s):  
Seung-Soon Im ◽  
Linda E. Hammond ◽  
Leyla Yousef ◽  
Cherryl Nugas-Selby ◽  
Dong-Ju Shin ◽  
...  
Keyword(s):  
Insertional Mutagenesis ◽  
Coenzyme A ◽  
Binding Protein ◽  
Regulatory Element ◽  
Fatty Acyl ◽  
Acetyl Coenzyme A ◽  
Acetyl Coenzyme ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Microarray Expression

ABSTRACT We generated a line of mice in which sterol regulatory element binding protein 1a (SREBP-1a) was specifically inactivated by insertional mutagenesis. Homozygous mutant mice were completely viable despite expressing SREBP-1a mRNA below 5% of normal, and there were minimal effects on expression of either SREBP-1c or -2. Microarray expression studies in liver, where SREBP-1a mRNA is 1/10 the level of the highly similar SREBP-1c, demonstrated that only a few genes were affected. The only downregulated genes directly linked to lipid metabolism were Srebf1 (which encodes SREBP-1) and Acacb (which encodes acetyl coenzyme A [acetyl-CoA] carboxylase 2 [ACC2], a critical regulator of fatty acyl-CoA partitioning between cytosol and mitochondria). ACC2 regulation is particularly important during food restriction. Similar to Acacb knockout mice, SREBP-1a-deficient mice have lower hepatic triglycerides and higher serum ketones during fasting than wild-type mice. SREBP-1a and -1c have identical DNA binding and dimerization domains; thus, the failure of the more abundant SREBP-1c to substitute for activating hepatic ACC2 must relate to more efficient recruitment of transcriptional coactivators to the more potent SREBP-1a activation domain. Our chromatin immunoprecipitation results support this hypothesis.

Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c

2003 ◽  
Vol 282 (2) ◽  
pp. 132-137 ◽  
Author(s):  
Y.u-A.n Yang ◽  
Patrice J. Morin ◽  
Wan Fang Han ◽  
Tinghua Chen ◽  
Daniel M. Bornman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Chronic exercise provides renal-protective effects with upregulation of fatty acid oxidation in the kidney of high fructose-fed rats

2020 ◽  
Vol 318 (3) ◽  
pp. F826-F834
Author(s):  
Gaizun Hu ◽  
Lusi Xu ◽  
Yixuan Ma ◽  
Masahiro Kohzuki ◽  
Osamu Ito
Keyword(s):  
Renal Function ◽  
Fatty Acid ◽  
Lipid Accumulation ◽  
Binding Protein ◽  
Regulatory Element ◽  
High Fructose ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Acyl Coa Oxidase ◽  
Renal Expression

Excessive fructose intake causes metabolic syndrome and lipid accumulation in the kidney and leads to renal dysfunction and damage. Exercise (Ex) improves lipids regulation, but the mechanisms are unclarified in the kidney. In the present study, male Sprague-Dawley rats were allocated to groups fed with control or high-fructose (HFr) diet. Part of rats in each group underwent aerobic treadmill Ex for 12 wk. Drug treatment was performed as the fenofibrate gavage during the last 4 wk on HFr diet-fed rats. Renal function, histological changes, and expression of regulators involved in fatty acid (FA) metabolism were assessed. In CON diet-fed groups, Ex did not affect renal function or histology and significantly increased renal expression of FA β-oxidation regulators including acyl-CoA dehydrogenases (CADs), acyl-CoA oxidase, peroxisome proliferator-activated receptor (PPAR)-α, and PPAR-γ coactivator (PGC)-1α and lipogenic factors including acetyl-CoA carboxylase (ACCα), FA synthase (FAS), and sterol regulatory element-binding protein 1c. HFr caused albuminuria, lipid accumulation, and renal pathohistological changes, which were attenuated by Ex but not by fenofibrate. HFr decreased renal expression of medium- and short-chain CADs and PPAR-α and increased renal expression of ACCα, FAS, and sterol regulatory element-binding protein 1c. Ex increased expression of CADs, carnitine palmitoyltransferase type I, acyl-CoA oxidase, PPAR-α, and PGC-1α and decreased renal expression of ACCα and FAS in HFr diet-fed rats. The Ex-induced FA metabolism alteration was similar to that in the fenofibrate-treated group. In conclusion, the present study indicates that Ex enhanced renal FA metabolism, which might protect the kidney in lipid dysregulation diseases.

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.

Sign in / Sign up

Export Citation Format

Share Document