scholarly journals Switching fatty acid metabolism by an RNA-controlled feed forward loop

2020 ◽  
Vol 117 (14) ◽  
pp. 8044-8054 ◽  
Author(s):  
Michaela Huber ◽  
Kathrin S. Fröhlich ◽  
Jessica Radmer ◽  
Kai Papenfort
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
High Throughput Sequencing ◽  
Acid Metabolism ◽  
Fatty Acid Biosynthesis ◽  
Sequencing Analysis ◽  
Rnase E ◽  
Human Pathogen ◽  
Feed Forward ◽  
Feed Forward Loop

Hfq (host factor for phage Q beta) is key for posttranscriptional gene regulation in many bacteria. Hfq’s function is to stabilize sRNAs and to facilitate base-pairing withtrans-encoded target mRNAs. Loss of Hfq typically results in pleiotropic phenotypes, and, in the major human pathogenVibrio cholerae, Hfq inactivation has been linked to reduced virulence, failure to produce biofilms, and impaired intercellular communication. However, the RNA ligands of Hfq inV. choleraeare currently unknown. Here, we used RIP-seq (RNA immunoprecipitation followed by high-throughput sequencing) analysis to identify Hfq-bound RNAs inV. cholerae. Our work revealed 603 coding and 85 noncoding transcripts associated with Hfq, including 44 sRNAs originating from the 3′ end of mRNAs. Detailed investigation of one of these latter transcripts, named FarS (fatty acid regulated sRNA), showed that this sRNA is produced by RNase E-mediated maturation of thefabB3′UTR, and, together with Hfq, inhibits the expression of two paralogousfadEmRNAs. ThefabBandfadEgenes are antagonistically regulated by the major fatty acid transcription factor, FadR, and we show that, together, FadR, FarS, and FadE constitute a mixed feed-forward loop regulating the transition between fatty acid biosynthesis and degradation inV. cholerae. Our results provide the molecular basis for studies on Hfq inV. choleraeand highlight the importance of a previously unrecognized sRNA for fatty acid metabolism in this major human pathogen.

scholarly journals ETV5 regulates hepatic fatty acid metabolism through PPAR signaling pathway

2020 ◽  
Author(s):  
Ada Admin ◽  
Zhuo Mao ◽  
Mingji Feng ◽  
Zhuoran Li ◽  
Minsi Zhou ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Association Studies ◽  
Sequencing Analysis ◽  
Dependent Manner ◽  
Alcoholic Fatty Liver ◽  
Hepatic Fatty Acid ◽  
Ppar Signaling

ETV5 is an ETS transcription factor which has been associated with obesity in genomic association studies. However, little is known about the role of ETV5 in hepatic lipid metabolism and non-alcoholic fatty liver disease (NAFLD). In the present study, we found that ETV5 protein expression was increased in diet- and genetic-induced steatotic liver. ETV5 responded to the nutrient status in an mTORC1 dependent manner and in turn regulated mTORC1 activity. Both viral-mediated and genetic depletion of ETV5 in mice led to increased lipid accumulation in the liver. RNA sequencing analysis revealed that PPAR signaling and fatty acid degradation/metabolism pathways were significantly downregulated in ETV5 deficient hepatocytes <i>in vivo</i> and <i>in vitro. </i>Mechanistically, ETV5 could bind to the PPRE region of PPAR downstream genes and enhance its transactivity. Collectively, our study identifies ETV5 as a novel transcription factor for the regulation of hepatic fatty acid metabolism which is required for the optimal β oxidation process. ETV5 may provide a therapeutic target for the treatment of hepatic steatosis.<br>

scholarly journals Anti-influenza A Virus Effects and Mechanisms of Emodin and Its Analogs via Regulating PPARα/γ-AMPK-SIRT1 Pathway and Fatty Acid Metabolism

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Yufei Bei ◽  
Boyu Tia ◽  
Yuze Li ◽  
Yingzhu Guo ◽  
Shufei Deng ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Influenza A Virus ◽  
Fatty Acid Metabolism ◽  
Influenza A ◽  
Acid Metabolism ◽  
Fatty Acid Biosynthesis ◽  
Sirtuin 1 ◽  
Peroxisome Proliferator ◽  
In Vivo Test

The peroxisome proliferator-activated receptor (PPAR) α/γ-adenosine 5 ′ -monophosphate- (AMP-) activated protein kinase- (AMPK-) sirtuin-1 (SIRT1) pathway and fatty acid metabolism are reported to be involved in influenza A virus (IAV) replication and IAV-pneumonia. Through a cell-based peroxisome proliferator responsive element- (PPRE-) driven luciferase bioassay, we have investigated 145 examples of traditional Chinese medicines (TCMs). Several TCMs, such as Polygonum cuspidatum, Rheum officinale Baillon, and Aloe vera var. Chinensis (Haw.) Berg., were found to possess high activity. We have further detected the anti-IAV activities of emodin (EMO) and its analogs, a group of common important compounds of these TCMs. The results showed that emodin and its several analogs possess excellent anti-IAV activities. The pharmacological tests showed that emodin significantly activated PPARα/γ and AMPK, decreased fatty acid biosynthesis, and increased intracellular ATP levels. Pharmaceutical inhibitors, siRNAs for PPARα/γ and AMPKα1, and exogenous palmitate impaired the inhibition of emodin. The in vivo test also showed that emodin significantly protected mice from IAV infection and pneumonia. Pharmacological inhibitors for PPARα/γ and AMPK signal and exogenous palmitate could partially counteract the effects of emodin in vivo. In conclusion, emodin and its analogs are a group of promising anti-IAV drug precursors, and the pharmacological mechanism of emodin is linked to its ability to regulate the PPARα/γ-AMPK pathway and fatty acid metabolism.

scholarly journals ETV5 regulates hepatic fatty acid metabolism through PPAR signaling pathway

2020 ◽  
Author(s):  
Ada Admin ◽  
Zhuo Mao ◽  
Mingji Feng ◽  
Zhuoran Li ◽  
Minsi Zhou ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Association Studies ◽  
Sequencing Analysis ◽  
Dependent Manner ◽  
Alcoholic Fatty Liver ◽  
Hepatic Fatty Acid ◽  
Ppar Signaling

ETV5 is an ETS transcription factor which has been associated with obesity in genomic association studies. However, little is known about the role of ETV5 in hepatic lipid metabolism and non-alcoholic fatty liver disease (NAFLD). In the present study, we found that ETV5 protein expression was increased in diet- and genetic-induced steatotic liver. ETV5 responded to the nutrient status in an mTORC1 dependent manner and in turn regulated mTORC1 activity. Both viral-mediated and genetic depletion of ETV5 in mice led to increased lipid accumulation in the liver. RNA sequencing analysis revealed that PPAR signaling and fatty acid degradation/metabolism pathways were significantly downregulated in ETV5 deficient hepatocytes <i>in vivo</i> and <i>in vitro. </i>Mechanistically, ETV5 could bind to the PPRE region of PPAR downstream genes and enhance its transactivity. Collectively, our study identifies ETV5 as a novel transcription factor for the regulation of hepatic fatty acid metabolism which is required for the optimal β oxidation process. ETV5 may provide a therapeutic target for the treatment of hepatic steatosis.<br>

scholarly journals Calcium-Phosphate Combination Enhances Spinosad Production in Saccharopolyspora Spinosa via Regulation of Fatty Acid Metabolism

2021 ◽  
Author(s):  
Miyang Wan ◽  
Cheng Peng ◽  
Wenxin Ding ◽  
Mengran Wang ◽  
Jinfeng Hu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Large Scale ◽  
Acid Metabolism ◽  
Fatty Acid Biosynthesis ◽  
De Novo ◽  
Control Treatment ◽  
Scale Production ◽  
Acid Biosynthesis ◽  
Inhibition Effect

Abstract Phosphate concentration above 10 mM reduces the production of many secondary metabolites; however, the phenomenon is not mechanistically understood yet. Specifically, the problem of phosphorus limitation in antibiotic production remains unresolved. This study investigates the phosphorus inhibition effect on spinosad production and alleviates it by calcium and phosphate supplementation to fermentation media. Furthermore, we examined the mechanism of fatty acids induced increase in polyketides production. NaH2PO4 was found to be the most effective phosphate. Under the optimal phosphate condition, the maximal spinosad production reached 520 mg/L, showing a 1.65-fold increase over the control treatment. In the NaH2PO4-CaCO3 system, the de novo fatty acid biosynthesis was significantly downregulated while spinosad biosynthesis and β-oxidation were upregulated. The coordination of de novo fatty acid biosynthesis and β-oxidation promoted intracellular acetyl-CoA concentration. The results demonstrate that NaH2PO4-CaCO3 combined addition is a simple and effective strategy to alleviate phosphorus inhibition effect through the regulation of fatty acid metabolism and accumulation of immediate precursors. This information improves our understanding of phosphates' influence on the large-scale production of polyketides.

The Influence of Lactate and Dipyridamole on Myocardial Fatty Acid Metabolism in Man, Traced with 123l-17-lodo-heptadecanoic Acid

1990 ◽  
Vol 29 (01) ◽  
pp. 28-34 ◽  
Author(s):  
F. C. Visser ◽  
M. J. van Eenige ◽  
G. Westera ◽  
J. P. Roos ◽  
C. M. B. Duwel
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Time Activity ◽  
Time Value ◽  
Myocardial Fatty Acid Metabolism ◽  
Coronary Vasodilatation ◽  
Activity Curve ◽  
Normal Human ◽  
Plasma Lactate Level

Changes in myocardial metabolism can be detected externally by registration of time-activity curves after administration of radioiodinated fatty acids. In this scintigraphic study the influence of lactate on fatty acid metabolism was investigated in the normal human myocardium, traced with 123l-17-iodoheptadecanoic acid (123l-17-HDA). In patients (paired, n = 7) lactate loading decreased the uptake of 123l-17-HDA significantly from 27 (control: 22-36) to 20 counts/min/pixel (16-31; p <0.05 Wilcoxon). The half-time value increased to more than 60 rriin (n = 5), oxidation decreased from 61 to 42%. Coronary vasodilatation, a well-known side effect of lactate loading, was studied separately in a dipyridamole study (paired, n = 6). Coronary vasodilatation did not influence the parameters of the time-activity curve. These results suggest that changes in plasma lactate level as occurring, among other effects, during exercise will influence the parameters of dynamic 123l-17-HDA scintigraphy of the heart.

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