scholarly journals Involvement of lipogenesis in the lower VLDL secretion induced by oligofructose in rats

1996 ◽  
Vol 76 (6) ◽  
pp. 881-890 ◽  
Author(s):  
N. Kok ◽  
M. Roberfroid ◽  
A. Robert ◽  
N. Delzenne
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Dietary Supplementation ◽  
Insulin Level ◽  
Hepatic Metabolism ◽  
Acid Synthesis ◽  
Metabolic Effect ◽  
Standard Diet ◽  
Male Wistar Rats

Dietary supplementation with oligofructose (OFS; 100 g/kg), a non-digestibleoligomer of β-D-fructose, decreases serum triacylglycerols in serum and VLDL of rats. In order to investigate the role of hepatic metabolism in the hypolipidaemic effect of OFS, male Wistar rats were fed on a standard diet with or without 1OOg Raftilose® P95/kg as OFS source for 30 d. OFS feeding (1) significantly decreased triacylglycerol and phospholipid concentrations in both blood and liver, (2) increased the glycerol-3-phosphate liver content but decreased the hepatic activity of glycerol-3-phosphate acyltransferase (EC 2.3.1.15), suggesting a decrease in acylglycerol synthesis, (3) did not affect the blood non-caterified fatty acid concentrations, but (4) reduced by 54% the capacity of isolated hepatocytesto synthesize and secrete triacylglycerols from labelled acetate; the activity of fatty acid synthase, a key lipogenic enzyme was also significantly decreased. These findings suggest that OFS decreases serum triacylglycerols by reducing de nova fatty acid synthesis in the liver; the lower insulin level in the serum of OFS-fed rats could explain, at least partly, the metabolic effect induced by such nondigestible carbohydrates.

scholarly journals Fatty Acid Synthase Is Involved in Classical Swine Fever Virus Replication by Interaction with NS4B

2021 ◽  
Author(s):  
Ya-Yun Liu ◽  
Xiao-Dong Liang ◽  
Chun-Chun Liu ◽  
Yan Cheng ◽  
Huan Chen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Classical Swine Fever Virus ◽  
Lipid Droplets ◽  
Fatty Acid Synthase ◽  
Classical Swine Fever ◽  
Acid Synthesis ◽  
Fever Virus ◽  
Viral Propagation

Classical swine fever virus (CSFV), a member of the genus Pestivirus of the family Flaviviridae , relies on host machinery to complete its life cycle. Previous studies have shown a close connection between virus infection and fatty acid biosynthesis, mainly regulated by fatty acid synthase (FASN). However, the molecular action of how FASN participates in CSFV replication remains to be elucidated. In this study, two chemical inhibitors of the fatty acid synthesis pathway (TOFA and C75) significantly impaired the late stage of viral propagation, suggesting CSFV replication required fatty acid synthesis. We next found that CSFV infection stimulated the expression of FASN, whereas knockdown of FASN inhibited CSFV replication. Furthermore, confocal microscopy showed that FASN participated in the formation of replication complex (RC), which was associated with the endoplasmic reticulum (ER). Interestingly, CSFV NS4B interacted with FASN and promoted overexpression of FASN, which is regulated by functional Rab18. Moreover, we found that FASN regulated the formation of lipid droplets (LDs) upon CSFV infection, promoting the virus proliferation. Taken together, our work provides mechanistic insight into the role of FASN in the viral life of CSFV, and it highlights the potential antiviral target for the development of therapeutics against pestiviruses. IMPORTANCE Classical swine fever, caused by CSFV, is one of the notifiable diseases by the World Organization for Animal Health (OIE) and causes significant financial losses to the pig industry globally. CSFV, like other (+) strand RNA viruses, requires lipid and sterol biosynthesis for efficient replication. However, the role of lipid metabolism in CSFV replication remains unknown. Here, we found that fatty acid synthase (FASN) was involved in viral propagation. Moreover, FASN is recruited to CSFV replication sites in the ER and interacts with NS4B to regulate CSFV replication that requires Rab18. Furthermore, we speculated lipid droplets (LDs) biosynthesis, indirectly regulated by FASN, ultimately promotes CSFV replication. Our results highlight a critical role for de novo fatty acid synthesis in CSFV infection, which might help control this devastating virus.

The Effect of γ-Hexachlorocyclohexane (Lindane) on the Activities of Liver Lipogenic Enzymes and on Serum Lipids in Rats

1995 ◽  
Vol 50 (1-2) ◽  
pp. 135-142 ◽  
Author(s):  
Meinrad Boll ◽  
Lutz W. D. Weber ◽  
Andreas Stampfl
Keyword(s):  
Fatty Acid ◽  
Enzyme Activities ◽  
Fatty Acid Synthase ◽  
Serum Triglyceride ◽  
Acid Synthesis ◽  
Dependent Manner ◽  
Lipogenic Enzymes ◽  
Serum Triglycerides ◽  
Male Wistar Rats ◽  
Substantial Decline

Abstract The effect of dietary γ-hexachlorocyclohexane (lindane) (50 -350 ppm, 0.17-1.19 μmol/kg chow) on the activity of enzymes of lipogenesis, viz., fatty acid synthase (FAS; EC 2.3.1.85), citrate cleavage enzyme (CCE; EC 4.1.3.8), malic enzyme (ME; EC 1.1.1.40), glucose-6-phosphate dehydrogenase (G 6 PDH; EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (PGDH; EC 1.1.1.44), and on serum lipid levels, was investigated in livers of 35-day-old male Wistar rats. Lindane (150 ppm) caused a substantial decline of enzyme activities within the first 24 h of treatment. The decrease was transient, however, and enzyme activities subsequently recov­ered despite continuation of lindane feeding. The recovery of enzyme activities was compara­ tively fast in the case of ME, G 6 PDH and PGDH, but very slow with FAS and CCE. Activities of lipogenic enzymes decrease when animals are starved, and increase much beyond prestarvation levels upon subsequent refeeding. Lindane in the refeeding diet blunted this overshoot of FAS and CCE activities in a dose-dependent manner. In contrast, activities of ME, G 6 PD H and PGDH responded to low dietary lindane concentrations with a substantial stimulation of the increase of activity, whereas at high lindane concentrations the overshoot was inhibited. According to their responses to lindane exposure, liver lipogenic enzymes could be grouped into 2 categories with FAS and CCE representing one and ME, G 6 PDH and PGDH representing the other group. Polychlorinated biphenyls (PCBs) in the diet caused basically opposite changes of the activities of the lipogenic enzymes. Co-administration of lindane and PCBs resulted in an apparent cancellation of effects, suggesting that lindane and PCBs affect fatty acid synthesis at opposite points. Levels of the serum triglycerides were increased significantly as a result of lindane feeding, while serum cholesterol and phospholipid levels were only slightly elevated. The increase of serum triglyceride levels that is routinely observed after refeeding of starved animals was stimulated even more by low concentrations of lindane in the refeeding diet, but inhibited by high concentrations.

Antiangiogenics and Hypoxic Response: Role of Fatty Acid Synthase Inhibitors

2016 ◽  
Vol 17 (15) ◽  
pp. 1735-1746 ◽  
Author(s):  
Maria Jose Bueno ◽  
Jesus Sanchez ◽  
Ramon Colomer ◽  
Miguel Quintela-Fandino
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Hypoxic Response

scholarly journals FSMP-15. EVALUATING THE ROLE OF LONG-CHAIN FATTY ACID METABOLISM IN PROMOTING GLIOBLASTOMA GROWTH

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i19-i19
Author(s):  
Divya Ravi ◽  
Carmen del Genio ◽  
Haider Ghiasuddin ◽  
Arti Gaur
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Survival Rate ◽  
Tumor Progression ◽  
Acid Synthesis ◽  
Normal Brain ◽  
Acid Uptake ◽  
Exogenous Fatty Acid ◽  
Long Chain

Abstract Glioblastomas (GBM) or Stage IV gliomas, are the most aggressive of primary brain tumors and are associated with high mortality and morbidity. Patients diagnosed with this lethal cancer have a dismal survival rate of 14 months and a 5-year survival rate of 5.6% despite a multimodal therapeutic approach, including surgery, radiation therapy, and chemotherapy. Aberrant lipid metabolism, particularly abnormally active de novo fatty acid synthesis, is recognized to have a key role in tumor progression and chemoresistance in cancers. Previous studies have reported a high expression of fatty acid synthase (FASN) in patient tumors, leading to multiple investigations of FASN inhibition as a treatment strategy. However, none of these have developed as efficacious therapies. Furthermore, when we profiled FASN expression using The Cancer Genome Atlas (TCGA) we determined that high FASN expression in GBM patients did not confer a worse prognosis (HR: 1.06; p-value: 0.51) and was not overexpressed in GBM tumors compared to normal brain. Therefore, we need to reexamine the role of exogenous fatty acid uptake over de novofatty acid synthesis as a potential mechanism for tumor progression. Our study aims to measure and compare fatty acid oxidation (FAO) of endogenous and exogenous fatty acids between GBM patients and healthy controls. Using TCGA, we have identified the overexpression of multiple enzymes involved in mediating the transfer and activation of long-chain fatty acids (LCFA) in GBM tumors compared to normal brain tissue. We are currently conducting metabolic flux studies to (1) assess the biokinetics of LCFA degradation and (2) establish exogenous versus endogenous LCFA preferences between patient-derived primary GBM cells and healthy glial and immune cells during steady state and glucose-deprivation.

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 Comparative analysis of the gut microbiota of mice fed a diet supplemented with raw and cooked beef loin powder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hye-Jin Kim ◽  
Dongwook Kim ◽  
Kwan-Woo Kim ◽  
Sang-Hoon Lee ◽  
Aera Jang
Keyword(s):  
Fatty Acid ◽  
Comparative Analysis ◽  
Gut Microbiota ◽  
Ribosomal Rna ◽  
Relative Abundance ◽  
Short Chain Fatty Acid ◽  
Dietary Supplementation ◽  
Acid Synthesis ◽  
Chain Fatty Acid ◽  
Increasing Trend

AbstractWe used 16S ribosomal RNA sequencing to evaluate changes in the gut microbiota of mice fed a diet supplemented with either raw or cooked beef loin powder for 9 weeks. Male BALB/c mice (n = 60) were randomly allocated to five groups: mice fed AIN-93G chow (CON), chow containing 5% (5RB) and 10% (10RB) raw beef loin powder, and chow containing 5% (5CB) and 10% (10CB) cooked beef loin powder. Dietary supplementation with both RB and CB increased the relative abundance of Clostridiales compared to the CON diet (p < 0.05). Mice fed 10RB showed a significantly higher relative abundance of Firmicutes (p = 0.018) and Lactobacillus (p = 0.001) than CON mice, and the ratio of Firmicutes/Bacteroidetes showed an increasing trend in the 10RB mice (p > 0.05). Mice fed 10CB showed a higher abundance of Peptostreptococcaceae and a lower abundance of Desulfovibrionaceae compared with the CON mice (p < 0.05). Genes for glycan biosynthesis, which result in short-chain fatty acid synthesis, were enriched in the CB mice compared to the RB mice, which was correlated to a high abundance of Bacteroides. Overall, dietary RB and CB changed the gut microbiota of mice (p < 0.05).

OC.04.6 EARLY DETECTION OF METACHRONOUS COLORECTAL CANCER: THE ROLE OF FATTY ACID SYNTHASE (FASN)

2016 ◽  
Vol 48 ◽  
pp. e85
Author(s):  
C. Riga ◽  
E. Corazziari ◽  
R. Murari ◽  
G. Pedullà ◽  
A. Pronio ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Early Detection ◽  
Fatty Acid Synthase ◽  
Metachronous Colorectal Cancer

scholarly journals The Role of Succinate in the Regulation of Fatty Acid Synthesis by Heart Mitochondria

1967 ◽  
Vol 242 (18) ◽  
pp. 4013-4022 ◽  
Author(s):  
Arthur F. Whereat ◽  
Franklin E. Hull ◽  
Margaret W. Orishimo ◽  
Joseph L. Rabinowitz
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Heart Mitochondria
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