scholarly journals The Effect of FATP1 on Adipocyte Differentiation in Qinchuan Beef Cattle

Animals ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2789
Author(s):  
Xuchun Liu ◽  
Shijun Li ◽  
Liyun Wang ◽  
Weiyi Zhang ◽  
Yujuan Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Acid Metabolism ◽  
Adipocyte Differentiation ◽  
Fat Metabolism ◽  
Signal Pathway ◽  
Regulation Mechanism ◽  
Rna Seq ◽  
Qinchuan Cattle ◽  
Preadipocyte Differentiation ◽  
Ppar Signaling

FATP1 plays an important role in the regulation of fatty acid metabolism and lipid accumulation. In this study, we investigated the patterns of FATP1 expression in various tissues obtained from calf and adult Qinchuan cattle, and in differentiating adipocytes. Next, we investigated the effect of FATP1 expression on preadipocyte differentiation in Qinchuan cattle using overexpression and interference assays. We also identified the differentially expressed genes (DEGs) and pathways associated with FATP1 overexpression/interference. Our results reveal that FATP1 was broadly expressed in heart, kidney, muscle, small intestine, large intestine, and perirenal fat tissues. While FATP1 overexpression promoted preadipocyte differentiation, fat deposition, and the expression of several genes involved in fat metabolism, FATP1 interference had the opposite effects on adipocyte differentiation. Following FATP1 overexpression and FATP1 interference in adipocytes, RNA-seq analysis was performed to identify DEGs related to fat metabolism. The DEGs identified include SLPI, STC1, SEMA6A, TNFRSF19, SLN, PTGS2, ADCYP1, FADS2, and SCD. Pathway analysis revealed that the DEGs were enriched in the PPAR signaling pathway, AMPK signal pathway, and Insulin signaling pathway. Our results provide an in-depth understanding of the function and regulation mechanism of FAPT1 in fat metabolism.

scholarly journals The Study of Yin-Chen-Hao-Tang Preventing and Treating Alcoholic Fatty Liver Disease Through PPAR Signaling Pathway Based on Network Pharmacology and RNA-Seq Transcriptomics

2021 ◽  
Author(s):  
Yi-Wei Zhu ◽  
Du Li ◽  
Ting-Jie Ye ◽  
Feng-Jun Qiu ◽  
Xiao-Ling Wang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Liver Tissue ◽  
Network Pharmacology ◽  
Rna Seq ◽  
Alcoholic Fatty Liver ◽  
Ppar Signaling ◽  
Alcoholic Fatty Liver Disease ◽  
Alt Activity

Abstract Background: Alcoholic fatty liver disease (AFLD) is the first stage of the alcoholic liver disease course. Yin-Chen-Hao-Tang (YCHT) has a good clinical effect on the treatment of AFLD, but its molecular mechanism has not been elucidated. In this study, we tried to explore the molecular mechanism of YCHT in improving hepatocyte steatosis in AFLD mice through network pharmacology and RNA sequencing (RNA-Seq) transcriptomics. Methods: Network pharmacological methods were used to analyze the potential therapeutic signaling pathways and targets of YCHT on AFLD. Then, the AFLD mice model was induced and YCHT was administered concurrently. Liver injury was measured by serum alanine aminotransferase (ALT) activity and liver tissue H&E staining, and liver steatosis was determined by serum triglyceride (TG) level and liver tissue Oil Red staining. The molecular mechanism of YCHT on prevention and treatment of mice AFLD was investigated according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differential expression genes data obtained by liver tissue RNA-Seq. Finally, the key signaling pathway and targets of YCHT on AFLD were verified in the ethanol-induced AFLD hepatocyte model by pathway inhibition experiments.Results: The results of network pharmacology analysis showed that YCHT may exert its pharmacological effect on AFLD through 312 potential targets which are involved in many signaling pathways including the PPAR signaling pathway. AFLD mice experiments results showed that YCHT markedly decreased mice serum ALT activity and serum TG levels. YCHT also significantly improved alcohol-induced hepatic injury and steatosis in mice livers. Furthermore, both KEGG analysis of RNA-Seq and AFLD hepatocyte model experiments showed that the PPAR signaling pathway should be the most relevant pathway of YCHT in the prevention and treatment of AFLD. YCHT could remarkably reduce the expression of PPARγ which is related to the lipogenesis pathway. YCHT also could increase the expression of PPARα which is related to the lipolysis pathway. Conclusions: Our study discovered that PPARγ and PPARα are the key targets and the PPAR signaling pathway is the main signaling pathway for YCHT to prevent and treat AFLD.

scholarly journals Downregulation of lncRNA PpL-T31511 and Pp-miRn182 Promotes Hydrogen Cyanamide-Induced Endodormancy Release through the PP2C-H2O2 Pathway in Pear (Pyrus pyrifolia)

2021 ◽  
Vol 22 (21) ◽  
pp. 11842
Author(s):  
Liang Li ◽  
Jinhang Liu ◽  
Qin Liang ◽  
Yu Feng ◽  
Chao Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Signal Pathway ◽  
Pyrus Pyrifolia ◽  
Aba Signaling ◽  
Rna Seq ◽  
Effective Measure ◽  
Hydrogen Cyanamide ◽  
Complex Process ◽  
Pp2c Gene

Bud endodormancy is an important, complex process subject to both genetic and epigenetic control, the mechanism of which is still unclear. The endogenous hormone abscisic acid (ABA) and its signaling pathway play important roles in the endodormancy process, in which the type 2C protein phosphatases (PP2Cs) is key to the ABA signal pathway. Due to its excellent effect on endodormancy release, hydrogen cyanamide (HC) treatment is considered an effective measure to study the mechanism of endodormancy release. In this study, RNA-Seq analysis was conducted on endodormant floral buds of pear (Pyrus pyrifolia) with HC treatment, and the HC-induced PP2C gene PpPP2C1 was identified. Next, software prediction, expression tests and transient assays revealed that lncRNA PpL-T31511-derived Pp-miRn182 targets PpPP2C1. The expression analysis showed that HC treatment upregulated the expression of PpPP2C1 and downregulated the expression of PpL-T31511 and Pp-miRn182. Moreover, HC treatment inhibited the accumulation of ABA signaling pathway-related genes and hydrogen peroxide (H2O2). Furthermore, overexpression of Pp-miRn182 reduced the inhibitory effect of PpPP2C1 on the H2O2 content. In summary, our study suggests that downregulation of PpL-T31511-derived Pp-miRn182 promotes HC-induced endodormancy release in pear plants through the PP2C-H2O2 pathway.

scholarly journals Transcriptomics analysis reveals the effect of Broussonetia papyrifera L. fermented feed on meat quality traits in fattening lamb

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11295
Author(s):  
Xuejiao An ◽  
Shengwei Zhang ◽  
Taotao Li ◽  
Nana Chen ◽  
Xia Wang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Meat Quality ◽  
Regulation Mechanism ◽  
Quality Traits ◽  
Rna Seq ◽  
Broussonetia Papyrifera ◽  
Meat Quality Traits ◽  
Sheep Meat ◽  
Fermented Feed ◽  
Ppar Signaling

To date, utilization of feed grains is increasing, which competes for human food. It is imperative to develop and utilize unconventional feed materials. Broussonetia papyrifera L. (B. papyrifera) is a good feeding material with high crude protein, crude fat, and low crude fiber, which is widely distributed in China. In this study, 12 Dorper ♂×Hu ♀  crossbred weaned male lambs were seleted into four groups based on the feed that ratio of the B. papyrifera fermented feed in the total mixed diet (0%, 6%, 18%, and 100%), to character the lambs’ longissimus dorsi (LD) fatty acids, morphology and transcriptome. Results showed that the muscle fiber’s diameter and area were the smallest in the 100% group. The highest content of beneficial fatty acids and the lowest content of harmful fatty acids in group 18%. RNA-seq identified 443 differentially expressed genes (DEGs) in the LD of lambs from 4 groups. Among these genes, 169 (38.1%) were up-regulated and 274 (61.9%) were down-regulated. The DEGs were mostly enriched in in fatty acid metabolism, arginine and proline metabolism, and PPAR signaling pathways. Our results provide knowledge to understand effect of different ratios of B. papyrifera fermented feed on sheep meat quality traits, also a basis for understanding of the molecular regulation mechanism of B. papyrifera fermented feed affecting on sheep meat quality.

scholarly journals Knockdown of ANGPTL4 May Reduce the Expression of LPL during Differentiation of 3T3-L1 Preadipocyte

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Zhao X ◽  
◽  
Zhang F ◽  
Liu Y ◽  
Liu H ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Energy Homeostasis ◽  
Adipocyte Differentiation ◽  
Adipocyte Size ◽  
Preadipocyte Differentiation ◽  
Similar Expression Pattern ◽  
Genes Expression ◽  
Before And After ◽  
Ppar Signaling

Adipose tissue is a complex, highly metabolically active tissue. The expansion of adipose tissue is mainly affected by two processes: the number of adipocytes and the change of adipocyte size. Adipocyte differentiation is regulated by multiple factors. 3T3-L1 preadipocyte line has become the most widely studied cell line for adipocyte proliferation, differentiation and regulation of related genes. In our previous study, we found that ANGPTL4 was related to preadipocyte differentiation through PPAR signaling pathway. Recent studies have shown that ANGPTL4 has functions of regulating oncogenesis, vascular permeability, glucose homeostasis, lipid metabolism, energy homeostasis. In this study, we observed the changes of key genes expression before and after inhibiting ANGPTL4 to explore how ANGPTL4 influence on lipid metabolism. Results shows that, ANGPTL4 and LPL have similar expression pattern. We suspect that, ANGPTL4 and LPL may form a pathway, when ANGPTL4 is suppressed it may block the pathway and inhibit LPL.

Potential use of homologous recombination deficiency score as an indicator of therapy selection in leiomyosarcoma patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23539-e23539
Author(s):  
Yuhong Zhou ◽  
Xi Guo ◽  
He Guo ◽  
Rongyuan Zhuang ◽  
Wenshuai Liu ◽  
...  
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Signaling Pathway ◽  
Somatic Mutation ◽  
Stage Iv ◽  
Parp Inhibitors ◽  
P Value ◽  
Rna Seq ◽  
Platinum Based Chemotherapy ◽  
Ppar Signaling

e23539 Background: Leiomyosarcoma (LMS) is one of the most frequent sarcoma subtypes. While surgical resection is the standard treatment of LMS, chemotherapy and radiation have shown additional survival benefit. However, the treatment response is variable and selection of appropriate agents is difficult due to the great heterogeneity of LMS. Matching DNA damaging reagents or PARP inhibitors, to tumors with a general homologous recombination deficit (HRD), can help to deploy these reagents more precisely. We explored the correlation of HRD score with the activation of PARP signaling pathway and retrospectively tested the effect of platinum-based therapy on an LMS patient with high HRD score. Methods: Nineteen LMS samples were subjected to whole exome sequencing and their HRD scores were calculated using a published algorithm. Nine of the LMS samples were also subjected to RNA-seq analysis and undergone GSEA to profile PARP pathway expression. CIBERSORT was employed to profile infiltrating immune cells. Results: The 19 LMS samples are defined as HRD-high (11 samples) or HRD-low (8 samples) if their HRD score is above or equal to, or below the medium respectively. For the 9 samples undergone RNA-seq, 97 genes have differential expression between the two groups (p-value < 0.05, fold change≥ 2). GSEA revealed 23 enriched pathways. Interestingly, PPAR signaling pathway is the most highly enriched one (EnrichmentScore = 0.506, P.adj = 0.005). No other pathogenic germline or somatic mutation in HRD related genes, for example BRCA1/2, is enriched. Additionally, high HRD score is significantly correlated with infiltrating Tregs, monocyte, and M0 macrophages as found in CIBERSORT analysis. To retrospectively test whether HRD score can be used to predict the response to inhibitors of DNA repair pathway, we identified one patient who had received platinum-based combination therapy after failure of first-line chemotherapy. The patient is a 40-year-old female with stage IV LMS and has a high HRD score. She achieved PR with 6-month PFS and remains progression free up to the abstract date, supporting a good correlation between high HRD score and advanced chemotherapy in LMS patients. Conclusions: High HRD score is correlated with activated PPAR pathway and infiltrating Tregs, monocytes and M0 macrophages, and can potentially be used to identify LMS patients with good response to platinum-based chemotherapy even though they have no obvious germline and somatic mutation in genes involved in DNA repair.

scholarly journals Comprehensive Analysis of the Transcriptome-Wide m6A Methylation Modification Difference in Liver Fibrosis Mice by High-Throughput m6A Sequencing

2021 ◽  
Vol 9 ◽  
Author(s):  
Chang Fan ◽  
Yanzhen Ma ◽  
Sen Chen ◽  
Qiumei Zhou ◽  
Hui Jiang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Stellate Cell ◽  
Endoplasmic Reticulum Stress Response ◽  
Systematic Evaluation ◽  
Joint Analysis ◽  
Rna Seq ◽  
Ppar Signaling ◽  
Additional Cell

N6-Methyladenosine (m6A), a unique and common mRNA modification method in eukaryotes, is involved in the occurrence and development of many diseases. Liver fibrosis (LF) is a common response to chronic liver injury and may lead to cirrhosis and even liver cancer. However, the involvement of m6A methylation in the development of LF is still unknown. In this study, we performed a systematic evaluation of hepatic genome-wide m6A modification and mRNA expression by m6A-seq and RNA-seq using LF mice. There were 3,315 genes with significant differential m6A levels, of which 2,498 were hypermethylated and 817 hypomethylated. GO and KEGG analyses illustrated that differentially expressed m6A genes were closely correlated with processes such as the endoplasmic reticulum stress response, PPAR signaling pathway and TGF-β signaling pathway. Moreover, a total of 90 genes had both a significant change in the m6A level and mRNA expression shown by joint analysis of m6A-seq and RNA-seq. Hence, the critical elements of m6A modification, including methyltransferase WTAP, demethylases ALKBH5 and binding proteins YTHDF1 were confirmed by RT-qPCR and Western blot. In an additional cell experiment, we also observed that the decreased expression of WTAP induced the development of LF as a result of promoting hepatic stellate cell (HSC) activation. Therefore, this study revealed unique differential m6A methylation patterns in LF mice and suggested that m6A methylation was associated with the occurrence and course of LF to some extent.

scholarly journals Network-based approach to identify biomarkers predicting response and prognosis for HER2-negative breast cancer treatment with taxane-anthracycline neoadjuvant chemotherapy

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7515 ◽  
Author(s):  
Cui Jiang ◽  
Shuo Wu ◽  
Lei Jiang ◽  
Zhichao Gao ◽  
Xiaorui Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Treatment ◽  
Signaling Pathway ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Breast Cancer Treatment ◽  
Chemotherapeutic Response ◽  
Ppar Signaling

Objective This study aims to identify effective gene networks and biomarkers to predict response and prognosis for HER2-negative breast cancer patients who received sequential taxane-anthracycline neoadjuvant chemotherapy. Materials and Methods Transcriptome data of training dataset including 310 HER2-negative breast cancer who received taxane-anthracycline treatment and an independent validation set with 198 samples were analyzed by weighted gene co-expression network analysis (WGCNA) approach in R language. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were performed for the selected genes. Module-clinical trait relationships were analyzed to explore the genes and pathways that associated with clinicopathological parameters. Log-rank tests and COX regression were used to identify the prognosis-related genes. Results We found a significant correlation of an expression module with distant relapse–free survival (HR = 0.213, 95% CI [0.131–0.347], P = 4.80E−9). This blue module contained genes enriched in biological process of hormone levels regulation, reproductive system, response to estradiol, cell growth and mammary gland development as well as pathways including estrogen, apelin, cAMP, the PPAR signaling pathway and fatty acid metabolism. From this module, we further screened and validated six hub genes (CA12, FOXA1, MLPH, XBP1, GATA3 and MAGED2), the expression of which were significantly associated with both better chemotherapeutic response and favorable survival for BC patients. Conclusion We used WGCNA approach to reveal a gene network that regulate HER2-negative breast cancer treatment with taxane-anthracycline neoadjuvant chemotherapy, which enriched in pathways of estrogen signaling, apelin signaling, cAMP signaling, the PPAR signaling pathway and fatty acid metabolism. In addition, genes of CA12, FOXA1, MLPH, XBP1, GATA3 and MAGED2 might serve as novel biomarkers predicting chemotherapeutic response and prognosis for HER2-negative breast cancer.

scholarly journals ETV5 Regulates Hepatic Fatty Acid Metabolism Through PPAR Signaling Pathway

Diabetes ◽  
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

scholarly journals TGF-β1-Mediated FDNCR1 Regulates Porcine Preadipocyte Differentiation via the TGF-β Signaling Pathway

Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1399
Author(s):  
Zhe Zhang ◽  
Yu Meng ◽  
Fei Gao ◽  
Yue Xiao ◽  
Yi Zheng ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Noncoding Rna ◽  
Adipocyte Differentiation ◽  
Transforming Growth Factor ◽  
Differentially Expressed ◽  
Mrna Levels ◽  
Preadipocyte Differentiation ◽  
Mesenchymal Transition ◽  
Tgf Β1

Adipocyte differentiation and lipid metabolism have important regulatory effects on the quality of meat from livestock. A variety of transcription factors regulate preadipocyte differentiation. Several studies have revealed that transforming growth factor-beta (TGF-β1) may play a key role in epithelial–mesenchymal transition (EMT); however, little is known about the effects of TGF-β1 treatment on porcine preadipocytes. To explore the role of TGF-β1 in porcine adipocyte differentiation, porcine preadipocytes were treated with 10 ng/mL TGF-β1, and two libraries were constructed for RNA-seq. We chose an abundant and differentially expressed long noncoding RNA (lncRNA), which we named fat deposition-associated long noncoding RNA1 (FDNCR1), for further study. RT-qPCR was used to detect mRNA levels of genes related to adipocyte differentiation. Triglyceride assay kits were used to detect lipid droplet deposition. TGF-β1 significantly suppressed porcine preadipocyte differentiation. We identified 8158 lncRNAs in total and 39 differentially expressed lncRNAs. After transfection with FDNCR1 siRNA, the mRNA expression of aP2, C/EBPα, and PPARγ and triglyceride levels significantly increased. Transfection with FDNCR1 siRNA significantly decreased protein levels of p-Smad2/Smad2 and p-Smad3/Smad3. These results demonstrate that FDNCR1 suppresses porcine preadipocyte differentiation via the TGF-β signaling pathway.

scholarly journals Transcriptome investigation of anti‐inflammation and immuno‐regulation mechanism of taurochenodeoxycholic acid

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lige Bao ◽  
Dacheng Hao ◽  
Xu Wang ◽  
Xiuling He ◽  
Wei Mao ◽  
...  
Keyword(s):  
Bile Acid ◽  
Signaling Pathway ◽  
Differentially Expressed Genes ◽  
Tissue Growth ◽  
Differentially Expressed ◽  
Regulation Mechanism ◽  
Rna Seq ◽  
Active Components ◽  
Anti Inflammatory ◽  
Regulatory Effects

Abstract Background Taurochenodeoxycholic acid (TCDCA) is one of the major active components in bile acid. It was proven to have inhibitory activities on inflammation and also participate in host immuno-regulation. TCDCA exerts anti-inflammatory and immuno-regulatory effects through the glucocorticoid receptor (GR) mediated genomic signaling pathway and the G protein-coupled bile acid receptor 5 (TGR5) mediated AC-cAMP-PKA signaling pathway. However, it is unclear whether GR or TGR5 plays an important role in the regulatory effects of TCDCA. In order to further investigate this effects mechanism of TCDCA, the research use the transcriptome to identify the major genes and pathway in the anti-inflammatory and immuno-regulatory effects. Methods After the Fibroblast-like synoviocytes (FLS) being treated by different concentrations (10− 5, 10− 6 and 10− 7 M) of TCDCA for 12 h, the resulting mRNA was analyzed by RNA-seq. The differentially expressed genes were screened from sequencing results using bioinformatics techniques. In the next step, other published literature were referred in order to find out whether those genes mentioned above are related to inflammation. The final selected differentially expressed genes associated with inflammation were then validated by q-PCR and western blot assays. Results Five genes associated with anti-inflammatory and immuno-regulatory effects, include Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Glutathione peroxidase 3 (GPX3), Serine/arginine-rich splicing factor-9 (SRSF9), Connective tissue growth factor (CTGF) and Cystatin B (CSTB) were identified. TCDCA at the concentrations of 10− 5, 10− 6 and 10− 7 M significantly (p < 0.05) up-regulate the mRNA and protein expression of SRSF9 and GPX3 and also up-regulate the mRNA expression of CSTB, CTGF and GAPDH. RNA-seq results of GPX3 and SRSF9 expression were consistent with q-PCR results, while q-PCR results of CTGF, GAPDH showed inconsistent with their RNA-seq results. Q-PCR result of CSTB expression also showed inconsistent with the RNA-seq result. Conclusions The anti-inflammatory and immuno-regulatory activities of TCDCA are proven to be related to the up-regulation expression of GPX3, SRSF9 and CSTB.

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