EXERCISE DOWN-REGULATION OF FATTY ACID SYNTHASE MAY BE CAUSED BY REDUCED NUCLEAR PROTEIN BINDING TO THE INSULIN AND CARBOHYDRATE RESPONSE ELEMENTS

1998 ◽  
Vol 30 (Supplement) ◽  
pp. 51
Author(s):  
R. Fiebig ◽  
M. Gore ◽  
L. Oscai ◽  
L. L. Ji
Keyword(s):  
Fatty Acid ◽  
Protein Binding ◽  
Fatty Acid Synthase ◽  
Nuclear Protein ◽  
Down Regulation ◽  
Response Elements

Exercise attenuates nuclear protein binding to gene regulatory sequences of hepatic fatty acid synthase

1999 ◽  
Vol 87 (3) ◽  
pp. 1009-1015 ◽  
Author(s):  
Russel Fiebig ◽  
Mitchell T. Gore ◽  
Li Li Ji
Keyword(s):  
Fatty Acid ◽  
Protein Binding ◽  
Fatty Acid Synthase ◽  
Nuclear Protein ◽  
Exhaustive Exercise ◽  
Regulatory Sequences ◽  
Transcription Rate ◽  
Response Element ◽  
Hepatic Fatty Acid ◽  
Fas Mrna

The effect of an acute bout of exhaustive exercise on hepatic fatty acid synthase (FAS) gene expression was examined in rats. Female Sprague-Dawley rats (age 8 wk) were fasted for 48 h (F, n = 6), or fasted, refed a high-fructose diet for 6 h, and killed at rest (R, n = 6) or killed after running on a treadmill at 27 m/min and 5% grade for 88 ± 7 min (E, n = 6). Gel mobility shift assay indicated that R rats had twofold higher liver nuclear protein binding to oligonucleotides corresponding to the insulin responsive sequence (−71/−50) and carbohydrate response element (+283/+303) on the FAS promoter, compared with F rats. Exercise severely attenuated this binding in liver nuclear extracts to the levels seen in F rats. Competition and supershift experiments revealed that the bound protein complexes contained the upstream stimulatory factors. Nuclear run-on experiment revealed a 49-fold increase in transcription rate of the FAS gene in R vs. F rats, whereas exercise suppressed the transcription rate. FAS mRNA abundance and FAS enzyme activity were dramatically increased with refeeding but were unaltered by exercise. The results reveal that dietary induction of hepatic FAS is stimulated by increased nuclear protein binding to insulin responsive sequence and carbohydrate response element, whereas exhaustive exercise attenuates the binding, which may precede downregulation of FAS mRNA and enzyme synthesis reported in our previous work (M. A. Griffiths, R. Fiebig, M. T. Gore, D. H. Baker, K. Esser, L. Oscai, and L. L. Ji. J. Nutr. 126, 1959–1971, 1996).

scholarly journals Gene expression pattern of acetyl-coA carboxylase alpha, fatty acid synthase, and stearoyl-CoA desaturase in pregnant Barki sheep under complete feed deprivation

2019 ◽  
pp. 8-13
Author(s):  
Ahmed El-Sayed ◽  
Ahmed Ateya ◽  
Mohamed Hamed ◽  
Sherif Shoieb ◽  
Hussam Ibrahim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Expression Pattern ◽  
Fatty Acid Synthase ◽  
Mrna Level ◽  
Gene Expression Pattern ◽  
Acetyl Coa Carboxylase ◽  
Down Regulation ◽  
Feed Deprivation ◽  
Stearoyl Coa Desaturase

Objective: To assess the mRNA level of acetyl CoA carboxylase alpha (ACACA), fatty acid synthase (FASN), and stearoyl-CoA desaturase (SCD) by means of real-time PCR in Barki sheep subjected to complete feed deprivation. Design: Controlled study. Animals: Seven healthy pregnant ewes. Procedures: Ewes were subjected to complete feed deprivation with ad libitum water for five consecutive days. Venous blood samples were collected from each ewe before (zero time) and on the fifth day post-deprivation of feed for measurement of the mRNA level of ACACA, FASN, and SCD and assessment of serum metabolic profile parameters. Results: On the fifth day post-fasting, the gene expression pattern of ACACA, FASN, SCD genes showed a significant (p < 0.05) down regulation in comparison with pre-deprivation of feed. There was a significant (p < 0.05) increase in the serum level of non-esterified fatty acids (NEFA), beta-hydroxyl buteric acid (BHBA), and triglycerides in pregnant ewes in the fifth day post-fasting in comparison with pre-deprivation of feed. On the other hand, there was a significant (p < 0.05) decrease in the level of glucose, cholesterol, and insulin in pregnant ewes in the fifth day post-fasting compared with pre-deprivation of feed. On histopathology, liver showed marked heptic steatosis in midzonal and periportal area, with formation of small fatty cysts in liver lobule. There was a positive correlation between leptin and insulin (r = 0.996; p < 0.01), BHB and leptin (r = 0.951; p < 0.05) and glucose and SCD (r = 1.0, p < 0.01). However, there was a negative correlation between FASN and NEFA (r = - 0.991; p < 0.05), FASN and leptin (r = -0.683; p < 0.05) and FASN and cholesterol (r = - 0.82; p < 0.05). Conclusion and clinical relevance: Pregnant Barki ewes can clinically tolerate complete feed deprivation for five days, with down regulation of ACACA, FASN, SCD genes and presence of marked metabolic changes. Therefore, metabolic monitoring is warranted to predict the early changes associated with feed deprivation under different stressful conditions.

Down-regulation of fatty acid synthase is associated with decreased Akt activation in lovastatin induced apoptosis cells

2020 ◽  
Vol 14 (4) ◽  
Author(s):  
Y.-C. Chang ◽  
Y.-H. Huang ◽  
C.-M. Shih ◽  
J.-Y. Wu ◽  
C.-L. Liu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Down Regulation ◽  
Akt Activation ◽  
Induced Apoptosis

DOWN REGULATION OF HEPATIC FATTY ACID SYNTHASE WITH ACUTE EXERCISE IN FASTED AND REFED RATS 593

1996 ◽  
Vol 28 (Supplement) ◽  
pp. 100
Author(s):  
R. Fiebig ◽  
M. Gore ◽  
L. L. Ji ◽  
M. A. Griffiths ◽  
K. Esser ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Acute Exercise ◽  
Down Regulation ◽  
Hepatic Fatty Acid

Down-regulation of fatty acid synthase increases the resistance of Saccharomyces cerevisiae cells to H2O2

2007 ◽  
Vol 43 (10) ◽  
pp. 1458-1465 ◽  
Author(s):  
A MATIAS ◽  
N PEDROSO ◽  
N TEODORO ◽  
H MARINHO ◽  
F ANTUNES ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Down Regulation

scholarly journals A Novel Factor Binding to the Glucose Response Elements of Liver Pyruvate Kinase and Fatty Acid Synthase Genes

1999 ◽  
Vol 274 (2) ◽  
pp. 1100-1107 ◽  
Author(s):  
Jun-ichi Hasegawa ◽  
Kiyoshi Osatomi ◽  
Ru-Feng Wu ◽  
Kosaku Uyeda
Keyword(s):  
Fatty Acid ◽  
Pyruvate Kinase ◽  
Fatty Acid Synthase ◽  
Glucose Response ◽  
Response Elements ◽  
Factor Binding

scholarly journals DNase I hypersensitivity sites and nuclear protein binding on the fatty acid synthase gene: identification of an element with properties similar to known glucose-responsive elements

1995 ◽  
Vol 308 (2) ◽  
pp. 521-527 ◽  
Author(s):  
F Foufelle ◽  
N Lepetit ◽  
D Bosc ◽  
N Delzenne ◽  
J Morin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Fatty Acid ◽  
Protein Binding ◽  
Pyruvate Kinase ◽  
Fatty Acid Synthase ◽  
Dnase I ◽  
Dnase I Footprinting ◽  
Nuclear Extracts ◽  
Rat Adipose Tissue

We have shown previously that fatty acid synthase (FAS) gene expression is positively regulated by glucose in rat adipose tissue and liver. In the present study, we have identified in the first intron of the gene a sequence closely related to known glucose-responsive elements such as in the L-pyruvate kinase and S14 genes, including a putative upstream stimulatory factor/major late transcription factor (USF/MLTF) binding site (E-box) (+ 292 nt to + 297 nt). Location of this sequence corresponds to a site of hypersensitivity to DNase I which is present in the liver but not in the spleen. Moreover, using this information from a preliminary report of the present work, others have shown that a + 283 nt to + 303 nt sequence of the FAS gene can confer glucose responsiveness to a heterologous promoter. The protein binding to this region has been investigated in vitro by a combination of DNase I footprinting and gel-retardation experiments with synthetic oligonucleotides and known nuclear proteins. DNase I footprinting experiments using a + 161 nt to + 405 nt fragment of the FAS gene demonstrate that a region from + 290 nt to + 316 nt is protected by nuclear extracts from liver and spleen. This region binds two ubiquitous nuclear factors, USF/MLTF and the CAAT-binding transcription factor/nuclear factor 1 (CTF/NF1). Binding of these factors is similar in nuclear extracts from liver which does or does not express the FAS gene as observed for glucose-responsive elements in the L-pyruvate kinase and S14 genes. This suggests a posttranslational modification of a factor of the complex after glucose stimulation.

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