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

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.

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 Integrative analysis of circRNAs, miRNAs, and mRNAs profiles to reveal ceRNAs networks in chicken intramuscular and abdominal adipogenesis

2020 ◽  
Author(s):  
Meng Zhang ◽  
Yu Han ◽  
Yanhui Zhai ◽  
Xiangfei Ma ◽  
Xinglan An ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Target Genes ◽  
Acid Metabolism ◽  
Adipogenic Differentiation ◽  
Expression Patterns ◽  
Fat Deposition ◽  
Circular Rnas ◽  
Tissue Specific ◽  
Functional Roles

Abstract Background: Tissue-specific fat deposition is regulated by a series of complex regulatory mechanisms. Reports indicate that epigenetic regulators, such as circular RNAs (circRNAs), are crucial in diseases progression, animal development, metabolism, and adipogenesis. In this study, to assess the functional roles of circRNAs in adipogenesis and tissue-specific fat deposition, we comprehensively analyzed the Ribo-Zero RNA-Seq and miRNAs data during chicken intramuscular and abdominal adipogenic differentiation. Results: circRNAs and miRNAs profiles during chicken adipogenic differentiation were found in adipocytes derived from various adipose tissues. It was also discovered that high levels of downregulated miRNAs potentially promote adipogenesis by activating their target genes which are associated with fatty acid metabolism and adipogenic differentiation. Through analysis of the correlation between the expression levels of circRNAs and adipogenic genes, as well as the dynamic expression patterns of circRNAs during adipogenic differentiation, several candidate circRNAs were identified. Moreover, competing endogenous RNA (ceRNAs) networks were constructed during chicken intramuscular and abdominal adipogenesis by combining miRNAs with mRNAs data. Several candidate circRNAs potentially influence adipogenesis by regulating miRNAs via PPAR and fatty acid metabolism-related pathways were identified, such as circLCLAT1, circFNDC3AL, circCLEC19A and circARMH1. Conclusion: In conclusion, our findings reveal that circRNAs and the circRNA-miRNAs-mRNAs-ceRNAs network may play important roles in chicken adipocytes differentiation and tissue-specific fat deposition.

scholarly journals Transcriptome analysis reveals potential mechanisms and pathways underlying embryonic development with respect to muscle growth and egg production in slow and fast growing chickens

2021 ◽  
Author(s):  
M. Kanakachari ◽  
R. Ashwini ◽  
R. N. Chatterjee ◽  
T. K Bhattacharya
Keyword(s):  
Fatty Acid ◽  
Signaling Pathways ◽  
Fatty Acid Metabolism ◽  
Egg Production ◽  
Muscle Development ◽  
Acid Metabolism ◽  
Muscle Growth ◽  
Differentially Expressed ◽  
Thigh Muscle ◽  
And Control

Abstract Background: Chicken is one of the important meat sources throughout the globe. Muscle development and egg production are important genetic traits in commercially raising chickens. However, not much information is available in the fast and slow growth of chicken to determine the expression of genes involved in muscle development and egg production in embryo initiation and developmental stages. This study was designed to investigate why improved Aseel (PD4) growing slowly compared with the control broiler (CB), microarray was conducted with the 7th-day embryo and 18th-day thigh muscle of improved Aseel (PD4) and control broiler (CL), respectively.Results: In the differential transcripts screening, all the transcripts obtained by microarray of slow and fast growth groups were screened by fold change ≥1 and false discovery rate (FDR) <0.05. In total, 19022 transcripts were differentially expressed between the 7th-day embryo and 18th-day thigh muscle of improved Aseel compared to the control broiler. Further analysis showed that a high number of transcripts are differentially regulated in the 7th-day improved Aseel embryo (15382) and fewer transcripts were differentially regulated (3640) in the 18th-day thigh muscle of improved Aseel compared to control broiler. In the 7th and 18th-day improved Aseel embryo, 10127, 2102, 5255, and 1538 transcripts were up and down-regulated, respectively. The commonly up and down-regulated transcripts are 545 and 381 between the 7th and 18th-day of embryos. In this study, we have selected 18 Gallus gallus candidate reference genes from NCBI and total RNA was isolated from control broiler, improved Aseel embryo tissues, and studied their expression profiles by real-time quantitative PCR (qPCR). The best housekeeping gene was identified by using geNorm, NormFinder, BestKeeper, Delta CT, and RefFinder analytical software. The result showed that the TFRC gene is the most stable and further it is used for qPCR data normalization. Further, to validate the differentially expressed genes (DEGs) related to muscle growth, myostatin signaling and development, fatty acid metabolism genes in improved Aseel (PD4) and control broiler embryo tissues by qPCR. Conclusion: Our study identified DEGs that regulate myostatin signaling and differentiation pathway, glycolysis and gluconeogenesis, fatty acid metabolism, Jak-STAT, mTOR, and TGF-β signaling pathways, tryptophan metabolism, PI3K-Akt signaling pathways in improved Aseel. The results revealed that the gene expression architecture is present in the improved Aseel exhibiting embryo growth that will help to improve muscle development, differentiation, egg production, as well as protein synthesis in improved Aseel native chicken. Our findings may be used as a model for improving the growth in improved Aseel as well as optimizing the growth in the control broiler.

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

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.

Abstract P028: Activation Of The Renin-angiotensin System Drives Renal Metabolic Abnormalities In Diabetic Nephropathy

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Kengo Azushima ◽  
Jean Paul Kovalik ◽  
Jianhong Ching ◽  
Susan B Gurley ◽  
Thomas M Coffman
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Renin Angiotensin System ◽  
Tca Cycle ◽  
High Grade ◽  
Wild Type ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Mitochondrial Fatty Acid

Activation of the renin-angiotensin system (RAS) is a major contributor to the pathogenesis of diabetic nephroathy (DN). However, the precise mechanisms of renoprotection associated with RAS blockade in DN are not entirely clear. The aim of this study is to examine whether metabolic effects of RAS blockade might contribute to renoprotection. We utilized a mouse model of DN combining severe type I diabetes (the Akita mutation) with a single-copy renin transgene (ReninTG) driven by the albumin promoter. Akita-ReninTG mice on a 129/Sv background (DN-susceptible mice) develop clinical features of human DN including high-grade albuminuria, renal interstitial inflammation and glomerulosclerosis, while Akita-ReninTG mice on a C57BL/6 background (DN-resistant mice) do not develop significant kidney disease. These two experimental groups were treated with the angiotensin receptor blocker (ARB) losartan 10 mg/kg/day for 12 weeks, and metabolic profiles in kidney tissues were examined using a targeted metabolomics assay. The DN-susceptible mice exhibited high-grade albuminuria that was significantly attenuated by ARB (Vehicle vs ARB: 1480±562 vs 193±42 μg/day, p =0.045), while DN-resistant mice had minimal albuminuria that was not affected by ARB (Vehicle vs ARB: 80±14 vs 75±14 μg/day, p =0.801). The metabolomics profiles of the DN-resistant mice were similar to C57BL/6 wild-type controls. By contrast, DN-susceptible mice exhibited broad reductions in even-chain acyl-carnitines and an abnormal profile of TCA cycle intermediates compared to 129/Sv wild-type controls, suggesting substantial impairments of renal mitochondrial fuel oxidation including altered fatty acid metabolism. RAS blockade had broad effects to correct this profile by increasing acetyl-carnitines generated from acetyl-CoA and concomitantly normalizing expression of genes associated with mitochondrial fatty acid metabolism including PPAR-α, PGC-1α, CPT1 and CPT2. ARB treatment restored TCA cycle activity to normal. These findings suggest that effects of RAS blockade re-establish normal fuel metabolism and mitochondrial fatty acid oxidation in kidney and may contribute to renoprotection.

scholarly journals Pemafibrate Protects against Fatty Acid-Induced Nephropathy by Maintaining Renal Fatty Acid Metabolism

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 372
Author(s):  
Daiki Aomura ◽  
Makoto Harada ◽  
Yosuke Yamada ◽  
Takero Nakajima ◽  
Koji Hashimoto ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Kidney Disease ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Male Mice ◽  
Histological Findings ◽  
Tubular Injury ◽  
Wild Type ◽  
Wild Type Male ◽  
And Oxidative Stress

As classical agonists for peroxisomal proliferator-activated receptor alpha (PPARα), fibrates activate renal fatty acid metabolism (FAM) and provide renoprotection. However, fibrate prescription is limited in patients with kidney disease, since impaired urinary excretion of the drug causes serious adverse effects. Pemafibrate (PEM), a novel selective PPARα modulator, is mainly excreted in bile, and, thus, may be safe and effective in kidney disease patients. It remains unclear, however, whether PEM actually exhibits renoprotective properties. We investigated this issue using mice with fatty acid overload nephropathy (FAON). PEM (0.5 mg/kg body weight/day) or a vehicle was administered for 20 days to 13-week-old wild-type male mice, which were simultaneously injected with free fatty acid (FFA)-binding bovine serum albumin from day 7 to day 20 to induce FAON. All mice were sacrificed on day 20 for assessment of the renoprotective effect of PEM against FAON. PEM significantly attenuated the histological findings of tubular injury caused by FAON, increased the renal expressions of mRNA and proteins related to FAM, and decreased renal FFA content and oxidative stress. Taken together, PEM exhibits renoprotective effects through the activation and maintenance of renal FAM and represents a promising drug for kidney disease.

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

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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