Multi–Omics Analysis of Key microRNA–mRNA Metabolic Regulatory Networks in Skeletal Muscle of Obese Rabbits

microRNAs (miRNAs), small non-coding RNA with a length of about 22 nucleotides, are involved in the energy metabolism of skeletal muscle cells. However, their molecular mechanism of metabolism in rabbit skeletal muscle is still unclear. In this study, 16 rabbits, 8 in the control group (CON–G) and 8 in the experimental group (HFD–G), were chosen to construct an obese model induced by a high–fat diet fed from 35 to 70 days of age. Subsequently, 54 differentially expressed miRNAs, 248 differentially expressed mRNAs, and 108 differentially expressed proteins related to the metabolism of skeletal muscle were detected and analyzed with three sequencing techniques (small RNA sequencing, transcriptome sequencing, and tandem mass tab (TMT) protein technology). It was found that 12 miRNAs and 12 core genes (e.g., CRYL1, VDAC3 and APIP) were significantly different in skeletal muscle from rabbits in the two groups. The network analysis showed that seven miRNA-mRNA pairs were involved in metabolism. Importantly, two miRNAs (miR-92a-3p and miR-30a/c/d-5p) regulated three transcription factors (MYBL2, STAT1 and IKZF1) that may be essential for lipid metabolism. These results enhance our understanding of molecular mechanisms associated with rabbit skeletal muscle metabolism and provide a basis for future studies in the metabolic diseases of human obesity.

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Multi-omics Analysis Reveals Whether and how Naphthylacetic Acid Affects the Quality of Rehmannia Glutinosa

10.21203/rs.3.rs-109124/v1 ◽

2020 ◽

Author(s):

Jianjun LI ◽

Luying SHAO ◽

Jialin ZHU ◽

Jingxiao MA ◽

Yanqing ZHOU ◽

...

Keyword(s):

Small Rna ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Differentially Expressed ◽

Small Rna Sequencing ◽

Rehmannia Glutinosa ◽

Degradome Sequencing ◽

Differentially Expressed Mirnas ◽

Naphthylacetic Acid

Abstract Background: Rehmannia glutinosa (R.glutinosa) is an important medicinal plant. The tuberous root of R.glutinosa is often used as herbal medicine. Naphthylacetic acid (NAA) as expansin can improve its yield, but knowledge about gene regulation and metabolome in its root is limited.Results: Full-length transcriptome, next generation transcriptome(NGS), small RNA and degradome sequencing and metabolomics were used to elucidate whether and how NAA affected its quality.30 differential expression metabolites (DEMs) (11 upregulated, 19downregulated) were identified, but catalpol and Rehmannioside D as quality standards were unchanged in its tuberous roots under control and NAA conditions (CKs and NTs); Their NGS identified 1,113 differentially expressed transcripts (DETs) (596 upregulated, 517downregulated) verified by RT-qPCR; Small RNA sequencing identified 78miRNAs (11known, 67 novel), of which 3 were differentially expressed miRNAs (1upregulated, 2downregulated). Among them, 274 differentially expressed miRNAs target transcripts (DEMTs) were predicted found and then validated by degradome sequencing; DETs and DEMTs were mainly related to metabolism. 4 miRNA-mRNA interaction pairs that regulates 4 metabolites (2 negatively correlated, 2 positively correlated) were identified; DETs, DEMs, differentially expressed miRNAs and DEMTs involved in phenylpropanoid biosynthesis regulated metabolites.Conclusions: The identification of DETs, DEMs, differentially expressed miRNAs and DEMTs could help to elucidate the regulatory networks and molecular mechanisms important for NAA-improving root quality of R.glutinosa.

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Untargeted Metabolomic Characteristics of Skeletal Muscle Dysfunction in Rabbits Induced by a High Fat Diet

10.21203/rs.3.rs-159084/v1 ◽

2021 ◽

Author(s):

Huimei Fan ◽

YanHong Li ◽

Jie Wang ◽

Jiahao Shao ◽

Tao Tang ◽

...

Keyword(s):

Skeletal Muscle ◽

High Fat Diet ◽

Metabolic Diseases ◽

Muscle Metabolism ◽

Principal Component ◽

Least Square ◽

Rabbit Skeletal Muscle ◽

Untargeted Metabolomics ◽

High Fat ◽

Skeletal Muscle Metabolism

Abstract Background: Type 2 diabetes and metabolic syndrome caused by a high fat diet (HFD) have become public health problems around the world. These diseases are characterized by disrupted mitochondrial oxidation and insulin resistance in skeletal muscle, but the mechanism is not clear. Therefore, this study aims to reveal how a high-fat diet induces skeletal muscle metabolism disorder.Methods：Sixteen weaned rabbits were randomly divided into two groups, one fed with a standard normal diet (SND) and another one fed a HFD for five weeks. Skeletal muscle tissue samples were extracted from each rabbit at the end of the 5-week trial. An untargeted metabolomics profiling was performed using ultraperformance liquid chromatography combined with mass spectrometry (UHPLC-MS/MS).Results: The HFD significantly altered the expression levels of phospholipids, LCACs, histidine, carnosine and tetrahydrocorticosterone in skeletal muscle. Principal component analysis (PCA) and least square discriminant analysis (PLS-DA) indicated that rabbit skeletal muscle metabolism in the HFD group was significantly up-regulated compared with that of the SND group. Among the 43 skeletal muscle metabolites in the HFD group, phospholipids, LCACs, histidine, carnosine and tetrahydrocorticosterone were identified as biomarkers for skeletal muscle metabolic diseases, and may also serve as potential physiological targets for related diseases in the future.Conclusion: The untargeted metabolomics analysis revealed that a HFD altered the rabbit skeletal muscle metabolism of phospholipids, carnitine, amino acids, and steroids. Notably, phospholipids, LCACs, histidine, carnosine and tetrahydrocorticosterone blocked the oxidative ability of mitochondria, and disturbed the oxidative ability of glucose and the fatty acid-glucose cycle in rabbit skeletal muscle.

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Transcriptome and miRNAome reveal components regulating primary thickening of bamboo shoots

10.1101/2021.09.23.461506 ◽

2021 ◽

Author(s):

Ying Li ◽

Deqiang Zhang ◽

Yongfeng Lou ◽

Xinmin An ◽

Zhimin Gao

Keyword(s):

Regulatory Networks ◽

Molecular Mechanisms ◽

Mirna Gene ◽

Wood Property ◽

Moso Bamboo ◽

Differentially Expressed ◽

Luciferase Reporter ◽

Thick Wall ◽

Small Rna Sequencing ◽

Bamboo Shoots

Primary thickening determines bamboo yield and wood property. However, little is known about the regulatory networks involved in this process. The present study identified a total of 58,652 genes and 521 miRNAs via transcriptome and small RNA sequencing using the underground thickening shoot samples of wild type (WT) Moso bamboo (Phyllostachys edulis) and a thick wall (TW) variant (P. edulis cv. Pachyloen) at five developmental stages (WTS1/TWS1-WTS5/TWS5). A total of 11,636 (54.05%) differentially expressed genes (DEGs) and 515 (98.85%) differentially expressed miRNAs (DEmiRs) were identified from the WT, TW, and WTTW groups. The first two groups were composed of four pairwise combinations each between two successive stages (WTS2/TWS2_vs_WTS1/TWS1, WTS3/TWS3_vs_WTS2/TWS2, WTS4/TWS4_vs_WTS3/TWS3 and WTS5/TWS5_vs_WTS4/TWS4), and the WTTW group was composed of five between two relative stages (TWS1-5_vs_WTS1-5). Additionally, among the phytohormones, zeatin (ZT) showed more remarkable changes in concentrations than indole-3-acetic acid (IAA), gibberellic acid (GA3), and abscisic acid (ABA) throughout the five stages in the WT and the TW groups. Moreover, 118 sites were identified for 590 miRNA-mRNA pairs via degradome sequencing. The dual-luciferase reporter assay confirmed that 14 miRNAs bound to 12 targets. Fluorescence in situ hybridization (FISH) localized miR166 and miR160 in the shoot apical meristem (SAM) and the procambium of Moso bamboo shoots at the S1 stage. Thus, primary thickening is a complex process regulated by miRNA-gene-phytohormone networks, and the miRNAome and transcriptome dynamics regulate phenotypic plasticity. These findings provide insights into the molecular mechanisms underlying wood formation and properties and propose targets for bamboo breeding.

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PSVII-2 Differentially expressed genes and their biological function in skeletal muscle of calves born from cows with or without protein supplementation during mid-gestation

Journal of Animal Science ◽

10.1093/jas/skaa054.293 ◽

2020 ◽

Vol 98 (Supplement_3) ◽

pp. 165-166

Author(s):

Elisa B Carvalho ◽

Letícia P Sanglard ◽

Karolina B Nascimento ◽

Javier M Meneses ◽

Daniel R Casagrande ◽

...

Keyword(s):

Skeletal Muscle ◽

Differentially Expressed Genes ◽

Muscle Development ◽

Negative Binomial ◽

Muscle Protein ◽

Basal Diet ◽

Protein Supplementation ◽

Differentially Expressed ◽

Control Group ◽

Q Value

Abstract Gestating cows have an increased nutrient demand to meet the needs of developing the fetus and the mid-gestation is a critical period for the fetal skeletal muscle development. The aim of this study was to evaluate the skeletal muscle transcriptome in the progeny as a function of the maternal protein nutrition during mid-gestation. Eleven Tabapuã cows and their male calves were used in this study. In the first third of gestation (0 to 100 days of gestation; dg), all cows were kept on pasture. From 100 to 200 dg, the control group (CTRL; 7 animals) received a basal diet achieving 5.5% crude protein (CP), whereas the supplemented group (SUPPL; 4 animals) received a basal diet plus protein supplementation (40% CP). After 200 dg, all animals received the same diet. Weaning was performed at 205 ± 7.5 days of age and animals were kept on pasture until reaching 240 days of age, when they were transferred to a feedlot. Muscle samples were collected at 260 days of age and RNA was extracted for RNA-seq analysis. Gene expression data was analyzed with a negative binomial model to identify (q-value ≤ 0.05) differentially expressed genes (DEG) between treatments. A total of 716 DEG were identified (289 DEG up-regulated and 427 down-regulated in SUPPL group; q-value ≤ 0.05). From the 10 most significant down-regulated DEG in the SUPPL group, two genes associated with apoptotic process were identified: MAPK8IP1 and GRINA, with log2 Fold-Changes (log2FC) of 1.04 and 0.49, respectively. From the 10 most significant up-regulated DEG in the SUPPL group, mTOR was identified, with log2FC=0.31. This is a well-known gene involved in muscle protein synthesis. In conclusion, maternal protein supplementation during mid-gestation affects the expression of genes related to energy metabolism and muscle development, which can lead to long-term impacts on production efficiency.

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Insights into the seasonal adaptive mechanisms of Chinese alligators (Alligator sinensis) from transcriptomic analyses

Australian Journal of Zoology ◽

10.1071/zo18005 ◽

2018 ◽

Vol 66 (2) ◽

pp. 93 ◽

Cited By ~ 4

Author(s):

Hongji Sun ◽

Xianbo Zuo ◽

Long Sun ◽

Peng Yan ◽

Fang Zhang ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Molecular Mechanisms ◽

Differentially Expressed ◽

Model Organisms ◽

Seasonal Adaptation ◽

Cold Temperatures ◽

Chinese Alligator ◽

Adaptive Mechanisms ◽

Alligator Sinensis

The Chinese alligator (Alligator sinensis) is an endemic and rare species in China, and is considered to be one of the most endangered vertebrates in the world. It is known to hibernate, an energy-saving strategy against cold temperatures and food deprivation. Changes in gene expression during hibernation remain largely unknown. To understand these complex seasonal adaptive mechanisms, we performed a comprehensive survey of differential gene expression in heart, skeletal muscle, and kidney of hibernating and active Chinese alligators using RNA-Sequencing. In total, we identified 4780 genes differentially expressed between the active and hibernating periods. GO and KEGG pathway analysis indicated the likely role of these differentially expressed genes (DEGs). The upregulated DEGs in the active Chinese alligator, CSRP3, MYG and PCKGC, may maintain heart and skeletal muscle contraction, transport and storage of oxygen, and enhance the body’s metabolism, respectively. The upregulated DEGs in the dormant Chinese alligator, ADIPO, CIRBP and TMM27, may improve insulin sensitivity and glucose/lipid metabolism, protect cells against harmful effects of cold temperature and hypoxia, regulate amino acid transport and uptake, and stimulate the proliferation of islet cells and the secretion of insulin. These results provide a foundation for understanding the molecular mechanisms of the seasonal adaptation required for hibernation in Chinese alligators, as well as effective information for other non-model organisms research.

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Altered miRNA and mRNA Expression in Sika Deer Skeletal Muscle with Age

Genes ◽

10.3390/genes11020172 ◽

2020 ◽

Vol 11 (2) ◽

pp. 172

Author(s):

Boyin Jia ◽

Yuan Liu ◽

Qining Li ◽

Jiali Zhang ◽

Chenxia Ge ◽

...

Keyword(s):

Skeletal Muscle ◽

Growth And Development ◽

Molecular Mechanisms ◽

Muscle Development ◽

Sika Deer ◽

De Novo ◽

Expression Profiles ◽

Differentially Expressed ◽

Growth Development ◽

Development And Aging

Studies of the gene and miRNA expression profiles associated with the postnatal late growth, development, and aging of skeletal muscle are lacking in sika deer. To understand the molecular mechanisms of the growth and development of sika deer skeletal muscle, we used de novo RNA sequencing (RNA-seq) and microRNA sequencing (miRNA-seq) analyses to determine the differentially expressed (DE) unigenes and miRNAs from skeletal muscle tissues at 1, 3, 5, and 10 years in sika deer. A total of 51,716 unigenes, 171 known miRNAs, and 60 novel miRNAs were identified based on four mRNA and small RNA libraries. A total of 2,044 unigenes and 11 miRNAs were differentially expressed between adolescence and juvenile sika deer, 1,946 unigenes and 4 miRNAs were differentially expressed between adult and adolescent sika deer, and 2,209 unigenes and 1 miRNAs were differentially expressed between aged and adult sika deer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that DE unigenes and miRNA were mainly related to energy and substance metabolism, processes that are closely associate with the growth, development, and aging of skeletal muscle. We also constructed mRNA–mRNA and miRNA–mRNA interaction networks related to the growth, development, and aging of skeletal muscle. The results show that mRNA (Myh1, Myh2, Myh7, ACTN3, etc.) and miRNAs (miR-133a, miR-133c, miR-192, miR-151-3p, etc.) may play important roles in muscle growth and development, and mRNA (WWP1, DEK, UCP3, FUS, etc.) and miRNAs (miR-17-5p, miR-378b, miR-199a-5p, miR-7, etc.) may have key roles in muscle aging. In this study, we determined the dynamic miRNA and unigenes transcriptome in muscle tissue for the first time in sika deer. The age-dependent miRNAs and unigenes identified will offer insights into the molecular mechanism underlying muscle development, growth, and maintenance and will also provide valuable information for sika deer genetic breeding.

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Integration of mRNA and miRNA Analysis Reveals the Molecular Mechanism Underlying Salt and Alkali Stress Tolerance in Tobacco

International Journal of Molecular Sciences ◽

10.3390/ijms20102391 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2391 ◽

Cited By ~ 3

Author(s):

Jiayang Xu ◽

Qiansi Chen ◽

Pingping Liu ◽

Wei Jia ◽

Zheng Chen ◽

...

Keyword(s):

Salinity Stress ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Crop Yields ◽

Antioxidant Activities ◽

Expression Patterns ◽

Differentially Expressed ◽

Alkali Stress ◽

Rna Seq ◽

Alkali Tolerance

Salinity is one of the most severe forms of abiotic stress and affects crop yields worldwide. Plants respond to salinity stress via a sophisticated mechanism at the physiological, transcriptional and metabolic levels. However, the molecular regulatory networks involved in salt and alkali tolerance have not yet been elucidated. We developed an RNA-seq technique to perform mRNA and small RNA (sRNA) sequencing of plants under salt (NaCl) and alkali (NaHCO3) stress in tobacco. Overall, 8064 differentially expressed genes (DEGs) and 33 differentially expressed microRNAs (DE miRNAs) were identified in response to salt and alkali stress. A total of 1578 overlapping DEGs, which exhibit the same expression patterns and are involved in ion channel, aquaporin (AQP) and antioxidant activities, were identified. Furthermore, genes involved in several biological processes, such as “photosynthesis” and “starch and sucrose metabolism,” were specifically enriched under NaHCO3 treatment. We also identified 15 and 22 miRNAs that were differentially expressed in response to NaCl and NaHCO3, respectively. Analysis of inverse correlations between miRNAs and target mRNAs revealed 26 mRNA-miRNA interactions under NaCl treatment and 139 mRNA-miRNA interactions under NaHCO3 treatment. This study provides new insights into the molecular mechanisms underlying the response of tobacco to salinity stress.

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Identification of Long Noncoding RNA Associated ceRNA Networks in Rosacea

BioMed Research International ◽

10.1155/2020/9705950 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Lian Wang ◽

Ruifeng Lu ◽

Yujia Wang ◽

Xiaoyun Wang ◽

Dan Hao ◽

...

Keyword(s):

Noncoding Rna ◽

Molecular Mechanisms ◽

Functional Enrichment ◽

Differentially Expressed ◽

Control Group ◽

Group 13 ◽

Regulatory Processes ◽

Coexpression Networks

Rosacea is a chronic and relapsing inflammatory cutaneous disorder with highly variable prevalence worldwide that adversely affects the health of patients and their quality of life. However, the molecular characterization of each rosacea subtype is still unclear. Furthermore, little is known about the role of long noncoding RNAs (lncRNAs) in the pathogenesis or regulatory processes of this disorder. In the current study, we established lncRNA-mRNA coexpression networks for three rosacea subtypes (erythematotelangiectatic, papulopustular, and phymatous) and performed their functional enrichment analyses using Gene Onotology, KEGG, GSEA, and WGCNA. Compared to the control group, 13 differentially expressed lncRNAs and 525 differentially expressed mRNAs were identified in the three rosacea subtypes. The differentially expressed genes identified were enriched in four signaling pathways and the GO terms found were associated with leukocyte migration. In addition, we found nine differentially expressed lncRNAs in all three rosacea subtype-related networks, including NEAT1 and HOTAIR, which may play important roles in the pathology of rosacea. Our study provided novel insights into lncRNA-mRNA coexpression networks to discover the molecular mechanisms involved in rosacea development that can be used as future targets of rosacea diagnosis, prevention, and treatment.

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MicroRNA dynamics during hibernation of the Australian central bearded dragon (Pogona vitticeps)

Scientific Reports ◽

10.1038/s41598-020-73706-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Alexander Capraro ◽

Denis O‘Meally ◽

Shafagh A. Waters ◽

Hardip R. Patel ◽

Arthur Georges ◽

...

Keyword(s):

Skeletal Muscle ◽

Physiological State ◽

Regulation Of Gene Expression ◽

Differentially Expressed ◽

Small Rna Sequencing ◽

Tissue Specific ◽

Mrna Targets ◽

Bearded Dragon ◽

Pogona Vitticeps ◽

Differentially Expressed Mrna

Abstract Hibernation is a physiological state employed by many animals that are exposed to limited food and adverse winter conditions. Controlling tissue-specific and organism wide changes in metabolism and cellular function requires precise regulation of gene expression, including by microRNAs (miRNAs). Here we profile miRNA expression in the central bearded dragon (Pogona vitticeps) using small RNA sequencing of brain, heart, and skeletal muscle from individuals in late hibernation and four days post-arousal. A total of 1295 miRNAs were identified in the central bearded dragon genome; 664 of which were novel to central bearded dragon. We identified differentially expressed miRNAs (DEmiRs) in all tissues and correlated mRNA expression with known and predicted target mRNAs. Functional analysis of DEmiR targets revealed an enrichment of differentially expressed mRNA targets involved in metabolic processes. However, we failed to reveal biologically relevant tissue-specific processes subjected to miRNA-mediated regulation in heart and skeletal muscle. In brain, neuroprotective pathways were identified as potential targets regulated by miRNAs. Our data suggests that miRNAs are necessary for modulating the shift in cellular metabolism during hibernation and regulating neuroprotection in the brain. This study is the first of its kind in a hibernating reptile and provides key insight into this ephemeral phenotype.

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Regulation of skeletal muscle mitochondrial function by nuclear receptors: implications for health and disease

Clinical Science ◽

10.1042/cs20150246 ◽

2015 ◽

Vol 129 (7) ◽

pp. 589-599 ◽

Cited By ~ 20

Author(s):

Joaquin Perez-Schindler ◽

Andrew Philp

Keyword(s):

Physical Activity ◽

Skeletal Muscle ◽

Nuclear Receptors ◽

Mitochondrial Biogenesis ◽

Mitochondrial Function ◽

Metabolic Diseases ◽

Therapeutic Potential ◽

Muscle Metabolism ◽

Cellular Level ◽

Expression Of Genes

Skeletal muscle metabolism is highly dependent on mitochondrial function, with impaired mitochondrial biogenesis associated with the development of metabolic diseases such as insulin resistance and type 2 diabetes. Mitochondria display substantial plasticity in skeletal muscle, and are highly sensitive to levels of physical activity. It is thought that physical activity promotes mitochondrial biogenesis in skeletal muscle through increased expression of genes encoded in both the nuclear and the mitochondrial genome; however, how this process is co-ordinated at the cellular level is poorly understood. Nuclear receptors (NRs) are key signalling proteins capable of integrating environmental factors and mitochondrial function, thereby providing a potential link between exercise and mitochondrial biogenesis. The aim of this review is to highlight the function of NRs in skeletal muscle mitochondrial biogenesis and discuss the therapeutic potential of NRs for the management and treatment of chronic metabolic disease.

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