A TetR-family transcription factor regulates fatty acid metabolism in the archaeal model organism Sulfolobus acidocaldarius

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 in vivo and in vitro. 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.

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Myostatin regulates fatty acid desaturation and fat deposition through MEF2C/miR222/SCD5 cascade in pigs

Communications Biology ◽

10.1038/s42003-020-01348-8 ◽

2020 ◽

Vol 3 (1) ◽

Author(s):

Hongyan Ren ◽

Wei Xiao ◽

Xingliang Qin ◽

Gangzhi Cai ◽

Hao Chen ◽

...

Keyword(s):

Transcription Factor ◽

Fatty Acid ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Muscle Growth ◽

Subcutaneous Fat ◽

Fat Deposition ◽

Wild Type ◽

Binding Prediction ◽

Stearoyl Coa Desaturase

Abstract Myostatin (MSTN), associated with the “double muscling” phenotype, affects muscle growth and fat deposition in animals, whereas how MSTN affects adipogenesis remains to be discovered. Here we show that MSTN can act through the MEF2C/miR222/SCD5 cascade to regulate fatty acid metabolism. We generated MSTN-knockout (KO) cloned Meishan pigs, which exhibits typical double muscling trait. We then sequenced transcriptome of subcutaneous fat tissues of wild-type (WT) and MSTN-KO pigs, and intersected the differentially expressed mRNAs and miRNAs to predict that stearoyl-CoA desaturase 5 (SCD5) is targeted by miR222. Transcription factor binding prediction showed that myogenic transcription factor 2C (MEF2C) potentially binds to the miR222 promoter. We hypothesized that MSTN-KO upregulates MEF2C and consequently increases the miR222 expression, which in turn targets SCD5 to suppress its translation. Biochemical, molecular and cellular experiments verified the existence of the cascade. This novel molecular pathway sheds light on new targets for genetic improvements in pigs.

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Interplay and cooperation between SREBF1 and master transcription factors regulate lipid metabolism and tumor-promoting pathways in squamous cancer

Nature Communications ◽

10.1038/s41467-021-24656-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Li-Yan Li ◽

Qian Yang ◽

Yan-Yi Jiang ◽

Wei Yang ◽

Yuan Jiang ◽

...

Keyword(s):

Transcription Factor ◽

Fatty Acid ◽

Lipid Metabolism ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Human Cancer ◽

Regulatory Element ◽

Regulatory Elements ◽

Gene Set Enrichment Analysis ◽

Transcriptional Dysregulation

AbstractSquamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63), a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify sterol regulatory element binding transcription factor 1 (SREBF1) as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/Kruppel like factor 5 (KLF5) is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC.

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ETV5 regulates hepatic fatty acid metabolism through PPAR signaling pathway

10.2337/figshare.13102934 ◽

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 in vivo and in vitro. 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.

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Effect of Guggulsterone on the Expression of Adiponectin in 3T3-L1 Cells

Natural Product Communications ◽

10.1177/1934578x1801300314 ◽

2018 ◽

Vol 13 (3) ◽

pp. 1934578X1801300

Author(s):

Indira Saikumar ◽

Avinash A. Rasalkar ◽

Bhadravathi M. Shivakumar ◽

Divijendra N. Reddy ◽

Rajyalakshmi Malempati

Keyword(s):

Developing Countries ◽

Transcription Factor ◽

Fatty Acid ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Mrna Levels ◽

Medical Conditions

Obesity is a worldwide threat, affecting both developed and developing countries. Guggulipid obtained from gum guggul is widely prescribed in Ayurveda for various medical conditions including obesity. The present study was designed to investigate the effect of guggulsterone on the expression of adiponectin, the adipokine that regulates glucose and fatty acid metabolism. 3T3-L1 cells were treated with guggulsterone E / Z isomer [(GE) /(GZ)] and mRNA levels of adiponectin as well as PPARγ (a transcription factor that regulates adiponectin expression) were monitored. Treatment of 3T3-L1 cells with GE / GZ during differentiation into adipocytes led to reduced mRNA levels of adiponectin. However, no effect on the mRNA levels of adiponectin was observed when fully differentiated adipocytes were treated with either GE or GZ.

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Transcription factor networks regulating hepatic fatty acid metabolism

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ◽

10.1016/j.bbalip.2014.05.001 ◽

2015 ◽

Vol 1851 (1) ◽

pp. 2-8 ◽

Cited By ~ 32

Author(s):

Panagiota Karagianni ◽

Iannis Talianidis

Keyword(s):

Transcription Factor ◽

Fatty Acid ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Hepatic Fatty Acid ◽

Transcription Factor Networks

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Cellular pathways during spawning induction in the starlet sea anemone Nematostella vectensis

10.1101/2021.03.16.435650 ◽

2021 ◽

Author(s):

Shelly Reuven ◽

Mieka Rinsky ◽

Vera Brekhman ◽

Assaf Malik ◽

Oren Levy ◽

...

Keyword(s):

Fatty Acid ◽

Sexual Reproduction ◽

Fatty Acid Metabolism ◽

Molecular Mechanisms ◽

Acid Metabolism ◽

Light Exposure ◽

Model Organism ◽

Sea Anemone ◽

Nematostella Vectensis ◽

Minor Effect

AbstractIn cnidarians, long-term ecological success relies on sexual reproduction. The sea anemone Nematostella vectensis, which has emerged as an important model organism for developmental studies, can be induced for spawning by temperature elevation and light exposure. To uncover molecular mechanisms and pathways underlying spawning, we characterized the transcriptome of Nematostella females before and during spawning induction. We identified an array of processes involving numerous receptors, circadian clock components, cytoskeleton, and extracellular transcripts that are upregulated upon spawning induction. Concurrently, processes related to the cell cycle, fatty acid metabolism, and other housekeeping functions are downregulated. Real-time qPCR revealed that light exposure has a minor effect on expression levels of most examined transcripts, implying that temperature change is a stronger inducer for spawning in Nematostella. Our findings reveal the mechanisms that may enable the mesenteries to serve as a gonad-like tissue for the developing oocytes and expand our understanding of sexual reproduction in cnidarians.Summary statementAnalysis of transcriptional changes during spawning induction in Nematostella vectensis, revealed upregulation of processes related to signal perception and cytoskeleton rearrangement and downregulation of fatty acid metabolism and housekeeping processes.

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

Nuklearmedizin ◽

10.1055/s-0038-1629509 ◽

1990 ◽

Vol 29 (01) ◽

pp. 28-34 ◽

Cited By ~ 1

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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