Proteomics insights into the effects of MSTN on muscle glucose and lipid metabolism in genetically edited cattle

Xin, Xiangbo; Yang, Shuping; Li, Xin; Liu, Xinfeng; Zhang, Lin-Lin; Ding, Xiangbin; Zhang, Sheng; Li, Guangpeng; Guo, Hong

doi:10.1016/j.ygcen.2019.113237

Cited by 28 publications

(23 citation statements)

References 51 publications

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“…Mounting evidence in animals has revealed the importance of MSTN in lipid metabolism. Transcriptomic analyses in MSTN knockout mouse, goat, and cattle showed that MSTN can affect a number of genes directly involved in fatty acid metabolism like SCD and ELOVL [33][34][35] , but the inherent link between MSTN and adipogenic genes has not been established. In this study, we took advantage of RNA-seq to identify the potential miRNA-mRNA regulatory pairs in the fat tissues of MSTN-KO and WT pigs.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…In addition to its effects on muscle development, MSTN also plays an important role in fat and glucose metabolism. The results of previous studies in our laboratory showed that knockout MSTN gene expression enhanced glycolysis and fat β-oxidation in bovine muscle tissue ( Yang et al, 2018 ; Xin et al, 2020 ). High levels of MSTN have been shown to cause muscle atrophy and are associated with a variety of diseases, such as cancer ( Aversa et al, 2012 ), chronic obstructive pulmonary disease ( Hayot et al, 2011 ), chronic heart failure ( Lenk et al, 2009 ), acquired immune deficiency syndrome ( Gonzalez-Cadavid et al, 1998 ), obesity, insulin resistance, and type 2 diabetes ( McPherron and Lee, 2002 ; Zhang et al, 2011 ; Zhang et al, 2012 ).…”

Section: Introductionmentioning

confidence: 79%

Proteomic Studies on the Mechanism of Myostatin Regulating Cattle Skeletal Muscle Development

et al. 2021

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Myostatin (MSTN) is an important negative regulator of muscle growth and development. In this study, we performed comparatively the proteomics analyses of gluteus tissues from MSTN+/− Mongolian cattle (MG.MSTN+/−) and wild type Mongolian cattle (MG.WT) using a shotgun-based tandem mass tag (TMT) 6-plex labeling method to investigate the regulation mechanism of MSTN on the growth and development of bovine skeletal muscle. A total of 1,950 proteins were identified in MG.MSTN+/− and MG.WT. Compared with MG.WT cattle, a total of 320 differentially expressed proteins were identified in MG.MSTN cattle, including 245 up-regulated differentially expressed proteins and 75 down-regulated differentially expressed proteins. Bioinformatics analysis showed that knockdown of the MSTN gene increased the expression of extracellular matrix and ribosome-related proteins, induced activation of focal adhesion, PI3K-AKT, and Ribosomal pathways. The results of proteomic analysis were verified by muscle tissue Western blot test and in vitro MSTN gene knockdown test, and it was found that knockdown MSTN gene expression could promote the proliferation and myogenic differentiation of bovine skeletal muscle satellite cells (BSMSCs). At the same time, Co-Immunoprecipitation (CO-IP) assay showed that MSTN gene interacted with extracellular matrix related protein type I collagen α 1 (COL1A1), and knocking down the expression of COL1A1 could inhibit the activity of adhesion, PI3K-AKT and ribosome pathway, thus inhibit BSMSCs proliferation. These results suggest that the MSTN gene regulates focal adhesion, PI3K-AKT, and Ribosomal pathway through the COL1A1 gene. In general, this study provides new insights into the regulatory mechanism of MSTN involved in muscle growth and development.

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“…This means that the presence of the mutation that disrupts the normal myostatin protein produces more effects than just the apparent excessive muscular growth and affects the activity of many key enzymes involved in fatty acid β-oxidation and glycolysis processes in cattle. Also, MSTN knockout triggers the activation of AMPK signaling pathways to regulate glucose and lipid metabolism by increasing the AMP/ATP ratio (Xin et al, 2019). The ability of MSTN to alter not only beef traits, but also meat and carcass quality, suggests a biological (rather than statistical) explanation for the particular scarcity of recent selection signatures in Asturiana de los Valles, where MSTN has fulfilled most of the plans of selection: few genomic regions were under strong selection in this breed because many phenotypic changes could be simultaneously obtained by acting on the MSTN gene alone.…”

Section: Discussionmentioning

confidence: 99%

Gene Banks as Reservoirs to Detect Recent Selection: The Example of the Asturiana de los Valles Bovine Breed

et al. 2021

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Gene banks, framed within the efforts for conserving animal genetic resources to ensure the adaptability of livestock production systems to population growth, income, and climate change challenges, have emerged as invaluable resources for biodiversity and scientific research. Allele frequency trajectories over the few last generations contain rich information about the selection history of populations, which cannot be obtained from classical selection scan approaches based on present time data only. Here we apply a new statistical approach taking advantage of genomic time series and a state of the art statistic (nSL) based on present time data to disentangle both old and recent signatures of selection in the Asturiana de los Valles cattle breed. This local Spanish originally multipurpose breed native to Asturias has been selected for beef production over the last few generations. With the use of SNP chip and whole-genome sequencing (WGS) data, we detect candidate regions under selection reflecting the effort of breeders to produce economically valuable beef individuals, e.g., by improving carcass and meat traits with genes such as MSTN, FLRT2, CRABP2, ZNF215, RBPMS2, OAZ2, or ZNF609, while maintaining the ability to thrive under a semi-intensive production system, with the selection of immune (GIMAP7, GIMAP4, GIMAP8, and TICAM1) or olfactory receptor (OR2D2, OR2D3, OR10A4, and 0R6A2) genes. This kind of information will allow us to take advantage of the invaluable resources provided by gene bank collections from local less competitive breeds, enabling the livestock industry to exploit the different mechanisms fine-tuned by natural and human-driven selection on different populations to improve productivity.

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Proteomics insights into the effects of MSTN on muscle glucose and lipid metabolism in genetically edited cattle

Cited by 28 publications

References 51 publications

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

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

Proteomic Studies on the Mechanism of Myostatin Regulating Cattle Skeletal Muscle Development

Gene Banks as Reservoirs to Detect Recent Selection: The Example of the Asturiana de los Valles Bovine Breed

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