scholarly journals Somatotropin-dependent decrease in fatty acid synthase mRNA abundance in 3T3-F442A adipocytes is the result of a decrease in both gene transcription and mRNA stability

1998 ◽  
Vol 331 (3) ◽  
pp. 815-820 ◽  
Author(s):  
Dezhong YIN ◽  
Steven D. CLARKE ◽  
Jana L. PETERS ◽  
Terry D. ETHERTON
Keyword(s):  
Fatty Acid ◽  
Mrna Stability ◽  
Fatty Acid Synthase ◽  
Insulin Treatment ◽  
Acid Synthesis ◽  
Mrna Abundance ◽  
Mrna Levels ◽  
Reporter Construct ◽  
Fas Mrna ◽  
Flanking Region

Somatotropin (ST) markedly decreases lipogenesis, fatty acid synthase (FAS) enzyme activity and mRNA abundance in pig adipocytes. The present study was conducted to determine whether the decrease in FAS mRNA in 3T3-F442A adipocytes was the result of a decrease in transcription of the FAS gene and/or a change in FAS mRNA stability. Insulin increased the abundance of FAS mRNA 2–13-fold and fatty acid synthesis 3–7-fold. Somatotropin decreased the stimulatory effect of insulin on the abundance of FAS mRNA and lipogenesis by 40–70% and 20–60% respectively. Subsequent run-on analyses demonstrated that the decrease observed in FAS mRNA in response to ST was associated with an 82% decrease in transcription; ST significantly shortened the half-life of FAS mRNA from 35 to 11 h. To corroborate the run-on analyses, cells were stably transfected with a pFAS–CAT5 (in which CAT stands for chloramphenicol acetyltransferase) reporter construct that contained 2195 bp of the 5´ flanking region of the rat FAS gene. Insulin treatment increased FAS–CAT activity 4.7-fold. When ST was added to the insulin-containing medium there was an approx. 60% reduction in FAS–CAT activity. In summary, our results indicate that ST decreases FAS mRNA levels and that this is the result of a marked decrease in both transcription of the FAS gene and stability of the FAS mRNA.

The growth hormone-dependent decrease in hepatic fatty acid synthase mRNA is the result of a decrease in gene transcription

1996 ◽  
Vol 16 (2) ◽  
pp. 151-158 ◽  
Author(s):  
S S Donkin ◽  
A D McNall ◽  
B S Swencki ◽  
J L Peters ◽  
T D Etherton
Keyword(s):  
Growth Hormone ◽  
Fatty Acid ◽  
Gene Transcription ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthase ◽  
Hormone Treatment ◽  
Mrna Abundance ◽  
Transcription Rate ◽  
Mrna Levels ◽  
Fas Mrna

ABSTRACT The present study was conducted to determine the chronic effects of porcine growth hormone administration on fatty acid synthase (FAS) mRNA abundance and gene transcription in growing rats. Growth hormone treatment increased growth rate approximately 27% (P<0·01). Porcine growth hormone decreased FAS mRNA levels by 55%. The reduction in FAS mRNA was due to a marked decrease in transcription of the FAS gene (decreased by 80%). In contrast, porcine growth hormone did not affect mRNA abundance or transcription rate of another insulin-regulated gene, phosphoenolpyruvate carboxykinase. In summary, our results have established that chronic treatment with growth hormone decreases FAS mRNA by decreasing the transcription rate of the gene. Furthermore, they suggest that the effects of growth hormone are specific and are not mediated by general changes in insulin-responsive gene expression in liver.

scholarly journals Catechins and Caffeine Inhibit Fat Accumulation in Mice through the Improvement of Hepatic Lipid Metabolism

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Chikako Sugiura ◽  
Shiho Nishimatsu ◽  
Tatsuya Moriyama ◽  
Sayaka Ozasa ◽  
Teruo Kawada ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Epigallocatechin Gallate ◽  
Acid Synthesis ◽  
Control Group ◽  
Mrna Levels ◽  
Fat Accumulation ◽  
Treatment Groups ◽  
Fas Mrna ◽  
Carnitine Palmitoyltransferase Ii

To elucidate the inhibiting mechanisms of fat accumulation by catechins, caffeine, and epigallocatechin gallate (EGCG), ICR mice were fed diets containing either 0.3% catechins or 0.1% EGCG and/or 0.05% caffeine for 4 weeks. After the feeding, intraperitoneal adipose tissues weights were significantly lower in the caffeine, catechins + caffeine, and EGCG + caffeine groups compared to controls. Hepatic fatty acid synthase (FAS) activity in the catechins + caffeine group was significantly lower, and the activities of acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase-II (CPT-II) were significantly higher, compared to the control group. However, these activities were not observed in the other groups. FAS mRNA expression levels in the catechins + caffeine group were significantly lower than in the control group. ACO and CPT-II mRNA levels were not different among all of the treatment groups. These findings indicate that the inhibitory effects of fat accumulation via a combination of catechins, EGCG, or caffeine were stronger collectively than by either catechins, EGCG, or caffeine alone. Moreover, it was demonstrated that the combination of catechins and caffeine induced inhibition of fat accumulation by suppression of fatty acid synthesis and upregulation of the enzymatic activities involved inβ-oxidation of fatty acid in the liver, but this result was not observed by combination of EGCG and caffeine.

scholarly journals 25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway

2008 ◽  
Vol 295 (6) ◽  
pp. E1369-E1379 ◽  
Author(s):  
Yongjie Ma ◽  
Leyuan Xu ◽  
Daniel Rodriguez-Agudo ◽  
Xiaobo Li ◽  
Douglas M. Heuman ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Synthase ◽  
Lipid Synthesis ◽  
Mrna Levels ◽  
Intracellular Lipids ◽  
Protein Levels ◽  
Regulatory Molecule ◽  
Fas Mrna

The oxysterol receptor LXR is a key transcriptional regulator of lipid metabolism. LXR increases expression of SREBP-1, which in turn regulates at least 32 genes involved in lipid synthesis and transport. We recently identified 25-hydroxycholesterol-3-sulfate (25HC3S) as an important regulatory molecule in the liver. We have now studied the effects of 25HC3S and its precursor, 25-hydroxycholesterol (25HC), on lipid metabolism as mediated by the LXR/SREBP-1 signaling in macrophages. Addition of 25HC3S to human THP-1-derived macrophages markedly decreased nuclear LXR protein levels. 25HC3S administration was followed by dose- and time-dependent decreases in SREBP-1 mature protein and mRNA levels. 25HC3S decreased the expression of SREBP-1-responsive genes, acetyl-CoA carboxylase-1, and fatty acid synthase (FAS) as well as HMGR and LDLR, which are key proteins involved in lipid metabolism. Subsequently, 25HC3S decreased intracellular lipids and increased cell proliferation. In contrast to 25HC3S, 25HC acted as an LXR ligand, increasing ABCA1, ABCG1, SREBP-1, and FAS mRNA levels. In the presence of 25HC3S, 25HC, and LXR agonist T0901317, stimulation of LXR targeting gene expression was repressed. We conclude that 25HC3S acts in macrophages as a cholesterol satiety signal, downregulating cholesterol and fatty acid synthetic pathways via inhibition of LXR/SREBP signaling. A possible role of oxysterol sulfation is proposed.

scholarly journals Reducing FASN expression sensitizes acute myeloid leukemia cells to differentiation therapy

2021 ◽  
Author(s):  
Magali Humbert ◽  
Kristina Seiler ◽  
Severin Mosimann ◽  
Vreni Rentsch ◽  
Katyayani Sharma ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Fatty Acid ◽  
Myeloid Leukemia ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Acid Synthesis ◽  
Mrna Levels ◽  
Differentiation Therapy ◽  
Granulocytic Differentiation ◽  
Acute Myeloid

AbstractFatty acid synthase (FASN) is the only human lipogenic enzyme available for de novo fatty acid synthesis and is often highly expressed in cancer cells. We found that FASN mRNA levels were significantly higher in acute myeloid leukemia (AML) patients than in healthy granulocytes or CD34+ hematopoietic progenitors. Accordingly, FASN levels decreased during all-trans retinoic acid (ATRA)-mediated granulocytic differentiation of acute promyelocytic leukemia (APL) cells, partially via autophagic degradation. Furthermore, our data suggest that inhibition of FASN expression levels using RNAi or (-)-epigallocatechin-3-gallate (EGCG) accelerated the differentiation of APL cell lines and significantly re-sensitized ATRA refractory non-APL AML cells. FASN reduction promoted translocation of transcription factor EB (TFEB) to the nucleus, paralleled by activation of CLEAR network genes and lysosomal biogenesis. Together, our data demonstrate that inhibition of FASN expression in combination with ATRA treatment facilitates granulocytic differentiation of APL cells and may extend differentiation therapy to non-APL AML cells.

Maternal dietary iron restriction modulates hepatic lipid metabolism in the fetuses

2005 ◽  
Vol 288 (1) ◽  
pp. R104-R111 ◽  
Author(s):  
Junlong Zhang ◽  
Rohan M. Lewis ◽  
Chunli Wang ◽  
Nicholas Hales ◽  
Christopher D. Byrne
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Synthase ◽  
Plasma Cholesterol ◽  
Liver Lipid ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Liver Cholesterol ◽  
Mrna Levels ◽  
Protein Levels

Maternal dietary Fe restriction reduced fasting plasma cholesterol and triglyceride (TG) concentrations in the fetuses, as well as decreased plasma TG levels in the adult offspring. To investigate how maternal Fe restriction was affecting fetal lipid metabolism, we investigated whether there were changes in liver lipid metabolism in the full-term fetuses. There was a ∼27% ( P < 0.05) increase in cholesterol but ∼29% reduction ( P = 0.01) in TG concentrations in the liver of the Fe-restricted fetuses. Hepatic mRNA levels of cholesterol 7α hydroxylase and liver X receptor-α (LXRα) were reduced by ∼50% ( P < 0.01) and ∼34% ( P < 0.01), respectively. As LXRα regulates expression of sterol response element binding protein-1c (SREBP-1c) expression, we measured SREBP-1c expression. There was an ∼43% ( P < 0.001) reduction in mRNA levels of SREBP-1c and its response genes, including acetyl-CoA carboxylase by ∼35% ( P = 0.01), fatty acid synthase by ∼18% ( P = 0.05), and diacylglycerol acyltransferase by ∼19% ( P = 0.03). Furthermore, protein levels of CD36 were reduced by ∼27% ( P = 0.02) in Fe-restricted fetuses. In conclusion, changes in liver cholesterol and TG concentrations in Fe-restricted fetuses may be coordinated through reduced expression of heme-containing cholesterol 7α hydroxylase and its regulator LXRα, mainly via downregulation of expression of genes in bile acid synthesis and fatty acid synthesis pathways.

Glucocorticoids increase fatty-acid synthase mRNA stability in fetal rat lung

1997 ◽  
Vol 272 (5) ◽  
pp. L860-L864 ◽  
Author(s):  
Z. X. Xu ◽  
S. A. Rooney
Keyword(s):  
Fatty Acid ◽  
Mrna Stability ◽  
Fatty Acid Synthase ◽  
Fetal Lung ◽  
Northern Analysis ◽  
Rat Lung ◽  
Fetal Rat ◽  
Fas Mrna ◽  
Fetal Rat Lung ◽  
Mrna Content

Fatty-acid synthase (FAS) is a critical enzyme in surfactant biosynthesis. In fetal lung, glucocorticoids increase synthesis of phosphatidylcholine, the principal lipid component of surfactant, and there is evidence that this effect is mediated by increased expression of the FAS gene. Dexamethasone increases FAS activity, mass, mRNA content, and rate of transcription in cultured explants of fetal rat lung. As previous experiments with actinomycin D suggested that dexamethasone may also increase FAS mRNA content by a posttranscriptional mechanism, we examined the effect of the hormone on FAS mRNA stability. Explants of 19-day fetal rat lungs were cultured for 44 h with and without 100 nM dexamethasone. Some explants were harvested at that point, and others were cultured further with 60 microM 5,6-dichlororibofuranosylbenzimidazole (DRB), an inhibitor of transcription. RNA was then extracted, and FAS mRNA levels were measured by Northern analysis, mRNA stability was assessed by comparing the amount remaining after culture with DRB with the initial level before addition of the inhibitor. The apparent half-life of FAS mRNA was 4 h in control explants cultured without hormone. FAS mRNA stability was increased 84% in the explants cultured with dexamethasone for 44 h and by 40% in those cultured with the hormone for 5 h. We conclude that glucocorticoids enhance expression of the FAS gene in fetal lung by increasing mRNA stability in addition to stimulating transcription.

Upregulation of adipocyte metabolism by agouti protein: possible paracrine actions in yellow mouse obesity

1996 ◽  
Vol 270 (1) ◽  
pp. E192-E196 ◽  
Author(s):  
B. H. Jones ◽  
J. H. Kim ◽  
M. B. Zemel ◽  
R. P. Woychik ◽  
E. J. Michaud ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Ectopic Expression ◽  
Acid Synthesis ◽  
Mrna Levels ◽  
Simultaneous Treatment ◽  
Agouti Protein ◽  
Agouti Gene

Mutations leading to ectopic expression of the murine agouti gene (a) result in progressive obesity. To further characterize this model, we analyzed adipose and hepatic mRNA levels for fatty acid synthase (FAS) and stearoyl-CoA desaturase (SCD), two key enzymes in de novo fatty acid synthesis and desaturation, respectively. FAS and SCD mRNA in both tissues of obese (Avy) mice were dramatically increased relative to lean (ala) controls. Excessive expression of these genes in this model could be due to direct effects of the agouti gene product; to test this possibility we treated 3T3-L1 adipocytes in vitro with recombinant agouti protein. Agouti treatment increased FAS and SCD mRNA levels by 1.5- and 4-fold, respectively. In addition, FAS activity and triglyceride content were 3-fold higher in agoutitreated 3T3-L1 cells relative to controls; these effects were attenuated by simultaneous treatment with a calcium channel blocker (nitrendipine). These data demonstrate that the agouti protein can directly increase lipogenesis in adipocytes and suggest that these effects are mediated through an intracellular calcium-dependent mechanism.

scholarly journals LINC00842 inactivates transcription co-regulator PGC-1α to promote pancreatic cancer malignancy through metabolic remodelling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xudong Huang ◽  
Ling Pan ◽  
Zhixiang Zuo ◽  
Mei Li ◽  
Lingxing Zeng ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Acid Synthesis ◽  
Ductal Adenocarcinoma ◽  
High Concentration ◽  
Metabolic Switch ◽  
Non Coding Rna ◽  
Xenograft Models ◽  
Transcription Factor Yy1 ◽  
Catabolic Process

AbstractThe molecular mechanism underlying pancreatic ductal adenocarcinoma (PDAC) malignancy remains unclear. Here, we characterize a long intergenic non-coding RNA LINC00842 that plays a role in PDAC progression. LINC00842 expression is upregulated in PDAC and induced by high concentration of glucose via transcription factor YY1. LINC00842 binds to and prevents acetylated PGC-1α from deacetylation by deacetylase SIRT1 to form PGC-1α, an important transcription co-factor in regulating cellular metabolism. LINC00842 overexpression causes metabolic switch from mitochondrial oxidative catabolic process to fatty acid synthesis, enhancing the malignant phenotypes of PDAC cells. High LINC00842 levels are correlated with elevated acetylated- PGC-1α levels in PDAC and poor patient survival. Decreasing LINC00842 level and inhibiting fatty acid synthase activity significantly repress PDAC growth and invasiveness in mouse pancreatic xenograft or patient-derived xenograft models. These results demonstrate that LINC00842 plays a role in promoting PDAC malignancy and thus might serve as a druggable target.

scholarly journals Glucose stimulates transcription of fatty acid synthase and malic enzyme in avian hepatocytes

1998 ◽  
Vol 274 (3) ◽  
pp. E493-E501 ◽  
Author(s):  
F. Bradley Hillgartner ◽  
Tina Charron
Keyword(s):  
Fatty Acid ◽  
High Fat Diet ◽  
Malic Enzyme ◽  
Fatty Acid Synthase ◽  
Primary Cultures ◽  
Pentose Phosphate ◽  
Mrna Abundance ◽  
Low Fat Diet ◽  
Low Carbohydrate

Transcription of fatty acid synthase (FAS) and malic enzyme (ME) in avian liver is low during starvation or feeding a low-carbohydrate, high-fat diet and high during feeding a high-carbohydrate, low-fat diet. The role of glucose in the nutritional control of FAS and ME was investigated by determining the effects of this metabolic fuel on expression of FAS and ME in primary cultures of chick embryo hepatocytes. In the presence of triiodothyronine, glucose (25 mM) stimulated an increase in the activity and mRNA abundance of FAS and ME. These effects required the phosphorylation of glucose to glucose 6-phosphate but not further metabolism downstream of the aldolase step of the glycolytic pathway. Xylitol mimicked the effects of glucose on FAS and ME expression, suggesting that an intermediate of the pentose phosphate pathway may be involved in mediating this response. The effects of glucose on the mRNA abundance of FAS and ME were accompanied by similar changes in transcription of FAS and ME. These data support the hypothesis that glucose plays a role in mediating the effects of nutritional manipulation on transcription of FAS and ME in liver.

Increased hepatic lipogenesis but decreased expression of lipogenic gene in adipose tissue in human obesity

2002 ◽  
Vol 282 (1) ◽  
pp. E46-E51 ◽  
Author(s):  
Frédérique Diraison ◽  
Eric Dusserre ◽  
Hubert Vidal ◽  
Monique Sothier ◽  
Michel Beylot
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Energy Restriction ◽  
Mrna Levels ◽  
Hepatic Lipogenesis ◽  
Deuterated Water ◽  
Human Obesity ◽  
Fas Mrna ◽  
Obese Subjects

To determine whether increased lipogenesis contributes to human obesity, we measured (postabsorptive state), in lean and obese subjects, lipid synthesis (deuterated water method) and the mRNA concentration (RT-competitive PCR) in subcutaneous adipose tissue of fatty acid synthase (FAS) and sterol regulatory element-binding protein (SREBP)-1c. Before energy restriction, obese subjects had an increased contribution of hepatic lipogenesis to the circulating triglyceride pool (14.5 ± 1.3 vs. 7.5 ± 1.9%, P < 0.01) without enhancement of cholesterol synthesis. This increased hepatic lipogenesis represented an excess of 2–5 g/day of triglycerides, which would represent 0.7–1.8 kg on a yearly basis. The lipogenic capacity of adipose tissue appeared, on the contrary, decreased with lower FAS mRNA levels ( P < 0.01) and a trend for decreased SREBP-1c mRNA ( P = 0.06). Energy restriction in obese patients decreased plama insulin ( P < 0.05) and leptin ( P < 0.05) and normalized hepatic lipogenesis. FAS mRNA levels were unchanged, whereas SREBP-1c increased. In conclusion, subjects with established obesity have an increased hepatic lipogenesis that could contribute to their excessive fat mass but no evidence for an increased lipogenic capacity of adipose tissue.

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