ETV5 regulates hepatic fatty acid metabolism through PPAR signaling pathway

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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A Model Construction of Starvation Induces Hepatic Steatosis and Transcriptome Analysis in Zebrafish Larvae

Biology ◽

10.3390/biology10020092 ◽

2021 ◽

Vol 10 (2) ◽

pp. 92

Author(s):

Hao Xu ◽

Yu Jiang ◽

Xiao-Min Miao ◽

Yi-Xi Tao ◽

Lang Xie ◽

...

Keyword(s):

Fatty Acid ◽

Hepatic Steatosis ◽

Fatty Acid Metabolism ◽

Transcriptome Analysis ◽

Acid Metabolism ◽

Fatty Acid Uptake ◽

Acid Uptake ◽

Alcoholic Fatty Liver ◽

Zebrafish Larvae ◽

Hepatic Fatty Acid

Hepatic steatosis caused by starvation, resulting in non-alcoholic fatty liver disease (NAFLD), has been a research topic of human clinical and animal experiments. To understand the molecular mechanisms underlying the triggering of abnormal liver metabolism by starvation, thus inducing hepatic lipid accumulation, we used zebrafish larvae to establish a starvation-induced hepatic steatosis model and conducted comparative transcriptome analysis by RNA-seq. We demonstrated that the incidence of larvae steatosis is positively correlated with starvation time. Under starvation conditions, the fatty acid transporter (slc27a2a and slc27a6-like) and fatty acid translocase (cd36) were up-regulated significantly to promote extrahepatic fatty acid uptake. Meanwhile, starvation inhibits the hepatic fatty acid metabolism pathway but activates the de novo lipogenesis pathway to a certain extent. More importantly, we detected that the expression of numerous apolipoprotein genes was downregulated and the secretion of very low density lipoprotein (VLDL) was inhibited significantly. These data suggest that starvation induces hepatic steatosis by promoting extrahepatic fatty acid uptake and lipogenesis, and inhibits hepatic fatty acid metabolism and lipid transport. Furthermore, we found that starvation-induced hepatic steatosis in zebrafish larvae can be rescued by targeting the knockout cd36 gene. In summary, these findings will help us understand the pathogenesis of starvation-induced NAFLD and provide important theoretical evidence that cd36 could serve as a potential target for the treatment of NAFLD.

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ETV5 Regulates Hepatic Fatty Acid Metabolism Through PPAR Signaling Pathway

Diabetes ◽

10.2337/db20-0619 ◽

2020 ◽

Vol 70 (1) ◽

pp. 214-226

Author(s):

Zhuo Mao ◽

Mingji Feng ◽

Zhuoran Li ◽

Minsi Zhou ◽

Langning Xu ◽

...

Keyword(s):

Fatty Acid ◽

Signaling Pathway ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Hepatic Fatty Acid ◽

Ppar Signaling

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1920753117 ◽

2020 ◽

Vol 117 (14) ◽

pp. 8044-8054 ◽

Cited By ~ 3

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.

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