scholarly journals Whole Transcriptome Analysis Reveals a Potential Regulatory Mechanism of LncRNA-FNIP2/miR-24-3p/FNIP2 Axis in Chicken Adipogenesis

Author(s):  
Lijin Guo ◽  
Xiaohuan Chao ◽  
Weiling Huang ◽  
Zhenhui Li ◽  
Kang Luan ◽  
...  

Lipid biosynthesis is a complex process, which is regulated by multiple factors including lncRNA. However, the role of lncRNA in chicken abdominal fat accumulation is still unclear. In this research, we collected liver tissues from six high abdominal fat rate Sanhuang broilers and six low abdominal fat rate Sanhuang broilers to perform lncRNA sequencing and small RNA sequencing. A total of 2,265 lncRNAs, 245 miRNAs, and 5,315 mRNAs were differently expressed. Among of them, 1,136 differently expressed genes were enriched in the metabolic process. A total of 36 differently expressed genes, which were considered as differently expressed lncRNAs’ targets, were enriched in the metabolic process. In addition, we also found out that eight differently expressed miRNAs could target 19 differently expressed genes. FNIP2 and PEX5L were shared in a cis-regulatory network and a differently expressed miRNA target relationship network. LncRNA-FNIP2/miR-24-3p/FNIP2 axis was considered as a potential candidate that may participate in lipid synthesis. Experimentally, the objective reality of lncRNA-FNIP2/miR-24-3p/FNIP2 axis was clarified and the regulation effect of lncRNA-FNIP2/miR-24-3p/FNIP2 axis on synthesis was validated. In brief, our study reveals a potential novel regulatory mechanism that lncRNA-FNIP2/miR-24-3p/FNIP2 axis was considered as being involved in lipid synthesis during chicken adipogenesis in liver.

2020 ◽  
pp. 109158182096151
Author(s):  
Jennifer C. Shing ◽  
Kai Schaefer ◽  
Shaun E. Grosskurth ◽  
Andy H. Vo ◽  
Tatiana Sharapova ◽  
...  

Predictive indicators of testicular toxicity could improve drug development by allowing early in-life screening for this adverse effect before it becomes severe. We hypothesized that circulating microRNAs (miRNAs) could serve as testicular toxicity biomarkers in dogs. Herein, we describe the results of an exploratory study conducted to discover biomarkers of drug-induced testicular injury. Following a dose-selection study using the testicular toxicant ethylene glycol monomethyl ether (EGME), we chose a dose of 50 mg/kg/d EGME to avoid systemic toxicity and treated 2 groups of dogs (castrated, non-castrated) for 14 to 28 days. Castrated animals were used as negative controls to identify biomarkers specific for testicular toxicity because EGME can cause toxicity to organ systems in addition to the testis. Blood was collected daily during the dosing period, followed by recovery for 29 to 43 days with less frequent sampling. Dosing was well tolerated, resulting in mild-to-moderate degeneration in testes and epididymides. Global profiling of serum miRNAs at selected dosing and recovery time points was completed by small RNA sequencing. Bioinformatics data analysis using linear modeling demonstrated several circulating miRNAs that were differentially abundant during the dosing period compared with baseline and/or castrated control samples. Confirmatory reverse transcription quantitative polymerase chain reaction data in these animals was unable to detect sustained alterations of miRNAs in serum, except for 1 potential candidate cfa-miR-146b. Taken together, we report the results of a comprehensive exploratory study and suggest future directions for follow-up research to address the challenge of developing diagnostic biomarkers of testicular toxicity.


2020 ◽  
Vol 48 (12) ◽  
pp. 6759-6774 ◽  
Author(s):  
Suhas R Seshadri ◽  
Chitra Banarjee ◽  
Mario H Barros ◽  
Flavia Fontanesi

Abstract Mitoribosome biogenesis is an expensive metabolic process that is essential to maintain cellular respiratory capacity and requires the stoichiometric accumulation of rRNAs and proteins encoded in two distinct genomes. In yeast, the ribosomal protein Var1, alias uS3m, is mitochondrion-encoded. uS3m is a protein universally present in all ribosomes, where it forms part of the small subunit (SSU) mRNA entry channel and plays a pivotal role in ribosome loading onto the mRNA. However, despite its critical functional role, very little is known concerning VAR1 gene expression. Here, we demonstrate that the protein Sov1 is an in bona fide VAR1 mRNA translational activator and additionally interacts with newly synthesized Var1 polypeptide. Moreover, we show that Sov1 assists the late steps of mtSSU biogenesis involving the incorporation of Var1, an event necessary for uS14 and mS46 assembly. Notably, we have uncovered a translational regulatory mechanism by which Sov1 fine-tunes Var1 synthesis with its assembly into the mitoribosome.


2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Tieshan Feng ◽  
Ping Lin ◽  
Jiao Gong ◽  
Dong Cheng ◽  
Xi Yang ◽  
...  

Bacillus bombyseptieus is a pathogen of Bombyx mori; it can cause bacterial septicemia in silkworm. One of the components of the parasporal crystal toxin of B. bombyseptieus, α-toxin, plays an important role in the process of infection in silkworm. In this study, we investigated the immune response of silkworm induced by α-toxin by using RNA-seq. We compared the changes in gene expression in the midgut, fatbody, and hemocytes of silkworm and in the B. mori embryonic cell line (BmE) after treatment with α-toxin and identified 952 differentially expressed genes and 353 differentially expressed long noncoding RNAs (lncRNAs). These regulated genes in different tissues were found to be enriched in different pathways. The upregulated genes in the midgut were mainly involved in peptidoglycan catabolic process and tyrosine kinase signaling pathway, whereas the downregulated genes were mainly involved in chitin metabolic pathways. The upregulated genes in fatbody were also involved in peptidoglycan catabolic process, but they were for a different peptidoglycan subtype. Further, genes encoding cecropins were enriched in the fatbody. The downregulated genes were mainly involved in the metabolic pathways of fundamental substances such as cellular protein metabolic process and nucleobase-containing compound metabolic process. These results suggest that α-toxin can induce various immune responses in silkworm, and further studies are warranted to understand the mechanism of α-toxin action in silkworm. Further, lncRNAs and differentially expressed genes were correlated using coexpression network analysis. Our findings revealed potential candidate genes and lncRNAs that might play important physiological functions in the immune response to α-toxins in silkworm.


2013 ◽  
Vol 80 (2) ◽  
pp. 165-173 ◽  
Author(s):  
Cinzia Marchitelli ◽  
Giovanna Contarini ◽  
Giovanna De Matteis ◽  
Alessandra Crisà ◽  
Lorraine Pariset ◽  
...  

In this work, the genetic variation of milk FA was investigated in three different bovine breeds, the Jersey, the Piedmontese and the Valdostana, and at different lactation stages. All animals were genotyped for 21 Single Nucleotide Polymorphisms located within nine candidate genes involved in lipid synthesis: diacylglycerol acyltransferase 1 and 2 (DGAT1, 2); stearoyl-CoA desaturase (SCD); growth hormone receptor (GHR); fatty acid synthase (FASN); acyl-CoA dehydrogenase (ACAD); fatty acid binding protein (FABP4); lipoprotein lipase (LPL); and leptin gene (LEP). The highest milk-fat Jersey breed also showed the highest content of saturated FA. Throughout lactation, the breeds showed a similar variation in the FA, with a decrease in the short-chain, this was accompanied by a general increase in the long chain FA at the end of lactation. The increase in long chain saturated FA was particularly evident in the case of the Jersey. The effect of SCD gene on the C14 desaturation index was confirmed; the DGAT1 gene was polymorphic only in the Jersey breed, but its effect was confirmed only on milk fat content; three further potential candidate genes were identified: first, the FABP4 gene, which was found to influence medium and long chain FA in all the breeds, but not the desaturation indices; second, the FASN gene, which was found to influence the amount of PUFA in the Piedmontese and the Valdostana, and third, the LPL gene, which was found to affect fat content in the Piedmontese.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lingling Shi ◽  
Jia Wang ◽  
Yujun Liu ◽  
Chao Ma ◽  
Sujuan Guo ◽  
...  

AbstractChinese chestnut (Castanea mollissima Blume) seed kernels (CCSK) with high quality and quantity of starch has emerged as a potential raw material for food industry, but the molecular regulatory mechanism of starch accumulation in developing CCSK is still unclear. In this study, we firstly analyzed the fruit development, starch accumulation, and microscopic observation of dynamic accumulation of starch granules of developing CCSK from 10 days after flowering (DAF) to 100 DAF, of which six representative CCSK samples (50–100 DAF) were selected for transcriptome sequencing analysis. Approximately 40 million valid reads were obtained, with an average length of 124.95 bp, which were searched against a reference genome, returning 38,146 unigenes (mean size = 1164.19 bp). Using the DESeq method, 1968, 1573, 1187, 1274, and 1494 differentially expressed unigenes were identified at 60:50, 70:60, 80:70, 90:80 and 100:90 DAF, respectively. The relationship between the unigene transcriptional profiles and starch dynamic patterns in developing CCSK was comparatively analyzed, and the specific unigenes encoding for metabolic enzymes (SUSY2, PGM, PGI, GPT, NTT, AGP3, AGP2, GBSS1, SS1, SBE1, SBE2.1, SBE2.2, ISA1, ISA2, ISA3, and PHO) were characterized to be involved potentially in the biosynthesis of G-1-P, ADPG, and starch. Finally, the temporal transcript profiles of genes encoding key enzymes (susy2, pgi2, gpt1, agp2, agp3, gbss1, ss1, sbe1, sbe2.1, sbe2.2, isa1, isa2, isa3, and pho) were validated by quantitative real-time PCR (qRT-PCR). Our findings could help to reveal the molecular regulatory mechanism of starch accumulation in developing CCSK and may also provide potential candidate genes for increasing starch content in Chinese chestnut or other starchy crops.


1981 ◽  
Vol 241 (5) ◽  
pp. C204-C208 ◽  
Author(s):  
J. C. Bartley ◽  
J. T. Emerman ◽  
M. J. Bissell

We have demonstrated that glycogen and lipid synthesis in adipocytes is modulated by the lactational state and that this modulation in mammary adipocytes requires the presence of the adjacent epithelial cells. Glycogen and lipid synthesis from [14C]glucose was measured in mammary fat pads cleared of epithelium, in abdominal fat pads, and in adipocytes from both sources and from intact mammary gland of mature virgin, pregnant, and lactating mice. Accumulation of glycogen, the activity of glycogen synthase, and the lipogenic rate in abdominal and mammary adipocytes remained high during pregnancy but decreased to insignificant levels by early lactation. The depressant effects of lactation were observed solely in those mammary adipocytes isolated from intact glands. The presence of mammary epithelial cells was also required to effect the stimulated lipogenesis in mammary adipocytes during pregnancy, We conclude that the metabolic activity of adipocytes is modulated both during pregnancy and lactation to channel nutrients to the mammary epithelial cell. The fact that the changes occur in mammary adipocytes only when epithelial cells are present indicates that local as well as systemic factors are operating in these modulations.


2021 ◽  
Author(s):  
Jayan Senevirathna ◽  
Ryo Yonezawa ◽  
Yoji Igarashi ◽  
Taiki Saka ◽  
Kazutoshi Yoshitake ◽  
...  

Abstract Jaw fats play a key role in echolocation in toothed whales. These fats are located along the outer and inner segments of the lower jawbone. A ribose nucleic acid (RNA) sequencing technique was employed to investigate transcriptomes of these two types of jaw fat tissues in Risso’s dolphins. We identified 1,899 upregulated common genes in both fat tissues. The differentially-expressed genes (DEGs) analysis showed that 34 and nine known genes were significantly upregulated in outer and inner jaw fats, respectively. A functional enrichment analysis was conducted by Enricher; lipid metabolism-related gene ontologies (GO) and pathways were identified (p<0.05). Based on these analyses, APOH, HNF4A, MYF6, SLC1A2, SLC2A2 and ALDOB were key genes for lipid metabolism in the outer jaw fat which are mainly involved with lipoprotein lipase activities. However, APP, DHX9, PXMP4 and THBS4 genes were highly expressed in the inner jaw fat, and their main functional enrichments were amyloid-beta formation and the activation of ECM-receptor interaction. These recent findings provide evidence for de novo lipid synthesis and as a new concept, the APP may be involved with transferring sound wave signals from the inner jaw fat to the brain via neurons, and further studies are necessary for revealing the puzzle of echolocation in toothed whales.


2020 ◽  
Author(s):  
Han Zhang ◽  
Xinxin Tong ◽  
Pan Yue ◽  
Jing Bai ◽  
Jinyan Yang ◽  
...  

Abstract Ophiocordyceps sinensis has been a source of valuable materials in traditional Asian medicine for over two thousand years. With recent global warming and overharvest, however, the availability of these wild fungi has decreased dramatically. While fruiting bodies of O. sinensis have been artificially cultivated, the molecular mechanisms that govern the induction of fruiting bodies at the transcriptional and post-transcriptional levels are unclear. In this study, we carried out both mRNA and small RNA sequencing to identify crucial genes and miRNA-like RNAs (milRNAs) involved in the development of fruiting bodies. A total of 2875 differentially expressed genes (DEGs) and 71 differentially expressed milRNAs (DEMs) were identified among the mycoparasite complex (MC), the sclerotium (ST) and the fruiting body (FB) stage. Functional enrichment and Gene Set Enrichment Analysis, analyses indicated that the ST had increased oxidative stress and energy metabolism, and that mitogen-activated protein kinase signaling might induce the formation of fruiting bodies. Integrated analysis of DEGs and DEMs revealed that n_os_milR16, n_os_milR21, n_os_milR34, and n_os_milR90 could be candidate milRNAs that regulate the induction of fruiting bodies. This study provides transcriptome-wide insight into the molecular basis of fruiting body formation in O. Sinensis, and identifies potential candidate genes for improving induction rate.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 866-866
Author(s):  
Xiangxiang Zhou ◽  
Xiaomin Chen ◽  
Yiqing Cai ◽  
Shunfeng Hu ◽  
Tiange Lu ◽  
...  

Abstract Introduction: N-6-methyladenosine (m 6A) is the most abundant modification in RNA and plays an important biological function in human diseases. YTHDF2 is an important m 6A reading protein, which could specifically bind to m 6A modified RNA and mediate its degradation. Here, we explored the functional significance and regulatory mechanism of YTHDF2 in diffuse large B-cell lymphoma (DLBCL), expecting to propose a novel therapeutic strategy. Methods: Lymph node biopsies from 80 de novo DLBCL patients and 20 reactive hyperplasia cases were collected with informed consents. The biological function of YTHDF2 was evaluated via constructing YTHDF2 stable knockdown and overexpression models, and CRISPR/Cas9 mediated genomic deletion. RNA-sequencing (RNA-seq) and lipidomic sequencing were conducted to detect the dysregulated RNA in YTHDF2-knockout DLBCL cells. m 6A methylation assays and dual-luciferase reporter assay were performed to explore the functional mechanism of YTHDF2. Xenograft DLBCL mice model was simultaneously established. Animal experiments were performed in accordance with the principles of the Institutional Animal Care. Results: We first evaluated the expression level of YTHDF2 and found the upregulation of YTHDF2 mRNA in DLBCL cells (Fig.1A-B). Survival analysis revealed that high YTHDF2 expression was associated with aggressive disease process (Fig.1C-E). High protein levels of YTHDF2 was validated in a cohort of newly diagnosed DLBCL patients (n=80) and DLBCL cell lines (Fig.1F). To explore the biological roles of YTHDF2, YTHDF2 knockdown (shYTHDF2) and overexpression models were performed. shYTHDF2 significantly impaired cell proliferation and induced cell cycle arrest (Fig.2A-B). Moreover, shYTHDF2 markedly triggered cell apoptosis and dysregulation of apoptotic proteins (Fig.2C). On the contrary, YTHDF2 overexpression resulted in reduced apoptosis (Fig.2D-E). To validate the involvement of YTHDF2 in DLBCL pathogenesis, we deleted YTHDF2 by CRISPR/Cas9 genomic-editing system (Fig.3A). Integrated analysis of mRNA expression profiles in sgYTHDF2 DLBCL cells was conducted by RNA-seq. GO analysis revealed that the differentially expressed genes (DEGs) were mainly enriched in cell cycle, RNA degradation and so on (Fig.3B). YTHDF2 deletion inhibited the proliferation and induced cell cycle attest in G2/M phase (Fig.3C-D). To further investigate the functions of YTHDF2 in vivo, xenograft DLBCL mice model was established. Mice bearing sgYTHDF2 tumors displayed reduced tumor growth and decreased Ki67 expression (Fig.3E). We next validated the functional mechanisms of YTHDF2 in DLBCL. KEGG pathway analysis revealed that the DEGs were mainly enriched in ceramide metabolic process, sphingolipid metabolic process, and sphingolipid signaling pathway. Given that the central effect of ceramide in the sphingolipid pathway, lipidomic sequencing was then performed. Partial Least Squares Method-Discriminant Analysis (PLS-DA) model revealed the valuable differences in lipid metabolite expression (Fig.4A). The screening results of differential lipid molecules exhibited 38 upregulated and 45 downregulated (Fig.4B). Consistently, depression of C18:1 and C22:0 ceramide was detected upon YTHDF2 deletion. Among them, ACER2 was downregulated upon YTHDF2 knockout, and positively linked to YTHDF2 expression (Fig.4C). Given that YTHDF2 is one of the m 6A binding proteins, we explored the global m 6A levels in DLBCL cells. Lower global m 6A level was showed in sgYTHDF2 DLBCL cells (Fig.4D). We primarily investigated the ACER2 mRNA sequence and discovered that 10 sequences were matched with the m 6A consensus sequence, 5'-RRACH-3', in the 3'-UTR. The luciferase activity of wild-type ACER2-fused reporter was obviously declinable in sgYTHDF2 cells, contrary to a remarkable augmentation in YTHDF2 overexpressed cells, whereas this impact was eliminated with the mutant ACER2-fused reporter. Moreover, YTHDF2 deletion inhibited ACER2 protein expression, which could be rescued by YTHDF2 elevation (Fig.4E). Conclusions: Our present study provides in vitro and in vivo pre-clinical evidence for the significance of YTHDF2 in lymphomagenesis and highlights the regulatory mechanism of YTHDF2 on ACER2-ceramide metabolic axis in DLBCL. Further investigations on the specific inhibitors of YTHDF2 in DLBCL will outline a promising therapeutic option in DLBCL therapy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ruili Liu ◽  
Xianxun Liu ◽  
Xuejin Bai ◽  
Chaozhu Xiao ◽  
Yajuan Dong

Fat metabolism is closely related to the economic characteristics of beef cattle. Therefore, regulating fat deposition and increasing intramuscular fat deposition are among the main goals of breeders. In this study, we aim to explore the regulatory role of CB1 gene on PPARγ2/PLIN1/HSL pathway in fat metabolism, and to further explore the differential expression of regulatory factors of this pathway in Shandong black cattle and Luxi cattle. In this study, CB1 overexpression stimulated lipid synthesis in adipocytes to some extent by increasing the levels of FASN and ACSL1. CB1 inhibitors reduce the lipid content in adipocytes and reduce the expression of GLUT1 and Insig1. In addition, overexpression of CB1 decreased the expression of PPARγ2 and led to an increase in PLIN1 expression and a decrease in HSL expression in adipocytes. We also found that the CB1/PPARγ2/PLIN1/HSL was differentially expressed in the different breeds of cattle and was involved in the regulation of fat metabolism, which affected the fatty acid content in the longissimus dorsi muscle of the two breeds. In short, CB1 participates in lipid metabolism by regulating HSL in the PPARγ2 and PLIN1 pathways, and improves lipid formation in adipocytes. In conclusion, CB1/PPARγ2/PLIN1/HSL pathway may be involved in the regulation of lipid metabolism.


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