Exercise performance and skeletal muscle homeostasis are influenced by myofiber type composition. Cysteine and glycine-rich protein 3 (CSRP3) is highly expressed in the oxidative fiber-rich mammalian soleus muscle. However, the mechanistic basis of CSRP3's involvement in skeletal muscle development and myofiber type specification remains unclear. Here, we used various exercise training (aerobic/anaerobic) bioinformatics datasets and experimental model systems involving live mice and cell lines to determine the role of CSRP3 in driving mitochondrial metabolic reconfiguration, skeletal muscle fiber type remodeling, and improved exercise endurance. CSRP3 promotes the formation of oxidative myofibers while suppressing glycolytic myofiber differentiation. It enhances mitochondrial biogenesis, oxidative phosphorylation capacity, and elevates mitochondrial membrane potential. Conversely, AAV-mediated CSRP3 knockdown perturbs mitochondrial energy metabolism, compromises exercise performance, and reduces the proportion of oxidative myofibers. Mechanistically, CSRP3 binds to D-lactate dehydrogenase (LDHD) via a specific 33-amino acid region, promoting D-lactate metabolism in skeletal muscle. This interaction regulates mitochondrial morphology, biogenesis, oxidative phosphorylation efficiency, and TCA cycle activity, ultimately driving skeletal muscle mitochondrial energy metabolic rewiring and skeletal muscle fiber type remodeling.
Bamei pigs, an indigenous Chinese breed, yield meat with a delectable flavor and boast higher carcass fat content compared to commercial breeds, making them a rich food source for humans. However, the differences in lipid and nutrient components between the adipose tissue of Bamei pigs and commercial pigs are still unclear. The study employed UPLC-MS/MS to quantify the composition of lipids and metabolites in the backfat of both Bamei and Large White pigs. A total of 428 lipids and 193 metabolites were significantly different between the 2 groups. Specifically, Bamei pig backfat exhibited altered levels of various lipids and metabolites that may potentially contribute to nutritional and flavor differences, including unsaturated triglycerides, free fatty acids, medium-chain triglycerides, essential amino acids, vitamins and antioxidants, while maintaining reduced cholesterol levels. Furthermore, we delved into the molecular mechanisms underlying these nutritional differences by analyzing significantly different 431 mRNAs and 865 proteins and integrating the regulatory network of protein-metabolite-lipid pathway. Importantly, in the pyruvate metabolic pathway of Bamei pigs, the bioprocess of lactate production was inhibited but the acetyl-CoA production was activated, suggesting the possibility that energy allocation favors the biogenesis of lipid precursors. These findings may contribute to guiding industrial food producers in enhancing the quality of lard at the genetic and molecular levels.
MicroRNAs (miRNAs) are key regulators of porcine myogenesis. In this study, we elucidated the regulatory role of miR-493-3p in skeletal muscle development. miR-493-3p showed a preferential expression pattern in skeletal muscle, with significantly higher expression in slow-twitch muscle than in fast-twitch muscle. Functional analyses revealed that overexpression of miR-493-3p inhibited the proliferation of porcine primary muscle satellite cells (MSCs) while promoting their differentiation and slow-twitch myofiber formation. In mouse, adeno-associated virus (AAV)-mediated overexpression of miR-493-3p significantly increased the cross-sectional area (CSA) of tibialis anterior muscle and promoted the proportion of slow-twitch myofibers. Furthermore, bioinformatic analysis and Dual-Luciferase Reporter Assay identified MAP kinase kinase 7 (MKK7) as a direct target of miR-493-3p. The miR-493-3p inhibited MKK7 expression, consequently reducing phosphorylated c-Jun N-terminal kinase (p-JNK) levels. Overall, our data demonstrate that miR-493-3p promotes porcine MSC differentiation and slow-twitch myofiber formation via inhibiting the MKK7/JNK axis. This finding enhances our understanding of miRNA-regulated skeletal muscle developmental networks and provides a potential strategy for improving pork production and meat quality.
The number of mummies (MUM) in pigs is a major factor affecting sow reproductive performance. Reducing the incidence of MUM can effectively improve sow utilization efficiency. However, the complex mechanisms by which the host genome, gut microbiome, and metabolome interact to influence sow MUM remain unclear. Based on the current research landscape, this study systematically reveals the regulatory mechanisms of the host genome-gut microbiome-metabolome interaction network on sow MUM. By conducting a multi-omics analysis on the intestinal contents of Yorkshire sows during late gestation across different parities, we constructed a dynamic atlas of the gut microbiota and identified 385 core microbial taxa. Through multi-model MWAS and meta-analysis, we screened six key microbial taxa significantly associated with MUM, including Bacteroidales_RF16_group, Prevotellaceae_Ga6A1_group, Comamonas, Paraprevotella, Dorea, and Gallicola. An mGWAS analysis further identified Bacteroidales_RF16_group as regulated by host genetics, as well as candidate genes such as EGF, ENPEP, and CASP6, and important SNP loci such as rs345237235 and rs3475666995. The study found that the abundance of Proteobacteria in the sow's gut increased progressively from the first parity, providing a theoretical basis for pathogen suppression mechanisms. By integrating fecal metabolomics data, we constructed a four-dimensional regulatory network of host gene-gut microbiota-metabolite-host phenotype. This study innovatively combines quantitative genetics with multi-omics approaches, not only providing a theoretical foundation for understanding host-microbiota interaction mechanisms but also offering critical scientific guidance for reducing sow MUM incidence and improving reproductive efficiency.
Estrus represents a critical phase in the porcine reproductive cycle and relies on functional ovarian development and coordinated steroidogenesis. Granulosa cells (GCs) mediate these processes by secreting estradiol (E 2) and progesterone (P 4), which are essential for follicular maturation and ovulatory competence. While circular RNAs (circRNAs) have been implicated in steroid hormone synthesis, their involvement in the regulation of gilt estrous remains unclear. In this study, circRNA sequencing was performed on ovarian tissues of estrus (ES) and non-estrus (NES) gilts, resulting in the identification of a novel circRNA, termed circular SHOC2 leucine rich repeat scaffold protein (circSHOC2), which exhibited marked up-regulation in ES ovaries. Functional assays demonstrated that circSHOC2 overexpression enhanced E 2 and P 4 synthesis and increased the protein levels of key steroidogenic enzymes. Mechanistic investigation revealed that circSHOC2 sponges miR-130b-5p. Silencing miR-130b-5p significantly enhanced E 2 and P 4 production, along with the up-regulation of steroidogenic proteins. Additionally, miR-130b-5p targeted ASH1-like histone lysine methyltransferase (ASH1L), while its overexpression significantly inhibited ASH1L. Cotransfection experiments revealed that ASH1L mitigated the inhibitory effects of miR-130b-5p on E 2 and P 4 synthesis in GCs. These findings establish a regulatory axis in which circSHOC2 modulates steroidogenic capacity in porcine GCs via the miR-130b-5p/ASH1L pathway, offering mechanistic insight into the molecular basis of gilt estrus and providing potential targets to enhance reproductive efficiency.
[This corrects the article DOI: 10.3389/fgene.2018.00293.].
BACKGROUND:Growth traits are economically important traits in pig breeding. However, the genetic mechanism of growth traits is still unclear. Qinchuan Black (QCB) pigs are crossbred and produced by hybridizing Guanzhong Black (GZB) pigs and Large White (LW) pigs, its characteristics include fast growth and excellent meat quality. In this study, whole genome and transcriptome analyses revealed the candidate genes associated with growth traits in QCB pigs based on imputed low-coverage whole-genome resequencing data. RESULTS:In total, we used 197 low-depth whole-genome resequencing data with an average depth of 3.5X, and then the data were imputed to resequencing data using SWIM reference panel, the imputation accuracy parameters, allele frequency r2 and concordance rate were 0.86 and 95.83%, respectively. We used two methods to investigate the candidate genes affecting the growth traits of QCB pigs, a total of 371 PSGs were identified, which related to muscle tissue development, tissue development and system development. A total of 30,489,782 SNPs were retained. A GWAS of ten growth traits by using fixed and random model circulating probability unification (FarmCPU) model, was performed in QCB pigs. We discovered seven genome wide significant SNPs and eight genome wide suggestive significant SNPs associated with body weight at 2 months (2-BW), body length at 2 months (2-BL), body height at 2 months (2-BH) and body height at 4 months (4-BH), and eighteen potential candidate genes were discovered. Transcriptomic data revealed that 18 differentially expression genes related to muscle and growth and development. Additionally, whole genome and transcriptome analyses found six genes (TENM3, CTNND2, RIMS1, PCDH7, ADGRL3 and CTNNA3) may affect the growth traits in Qinchuan Black pigs. CONCLUSION:Our study shows that more candidate genes associated with pig growth traits can be identified by whole genome and transcriptome analyses. We found that six genes may be new key candidate genes affecting pig growth traits. In conclusion, this study elucidated the molecular genetic mechanisms of growth traits and identified new molecular breeding targets, offering a robust scientific basis for advancing breeding strategies and genetic investigations within this breed.
The Bamei pigs (BM), an indigenous breed in Northwest China, is renowned for its superior meat quality. To uncover the genetic basis of its traits, we analyzed whole-genome sequencing data from 61 BM. Our results revealed that BM have a good genetic conservation status and distinct genomic divergence from Western breeds. We identified MALSU1 as a new candidate gene associated with intramuscular fat (IMF) by integrating selection signature analysis with public databases, such as PigGTEx, PigBiobank, and PigQTL. Overexpression and interference experiments of MALSU1 demonstrated that it regulates IMF by inhibiting the proliferation and promoting the differentiation of porcine intramuscular adipocyte primary cells. RNA-seq results further revealed that MALSU1 regulates IMF by inhibiting lipid metabolism and promoting lipid synthesis. Interestingly, a missense mutation (p.Arg10Leu) in the coding region of the MALSU1 gene was identified, which could promote the proliferation of intramuscular preadipocytes, suggesting an important role in IMF deposition.
Sophoridine (SRP) is a natural quinolizidine alkaloid found in many traditional Chinese herbs, though its effect on adipose tissue is unclear. We improved serum lipid levels by administering SRP by gavage in high-fat diet (HFD)-fed C57BL/6 mice. After 11 weeks, SRP supplementation significantly reduced body weight gain and improved glucose homeostasis, while reducing subcutaneous fat and liver weight. SRP also inhibited cell proliferation and differentiation of 3T3-L1 cells. Proteomics analysis revealed that SRP inhibits adipocyte differentiation by interacting with Src, thereby suppressing vascular endothelial growth factor receptor 2 (VEGFR2) expression and PI3K/AKT phosphorylation. This study provides an empirical basis for the treatment of obesity with small molecules.
BackgroundTeat number is one of the most important indicators to evaluate the lactation performance of sows, and increasing the teat number has become an important method to improve the economic efficiency of farms. Therefore, it is particularly important to deeply analyze the genetic mechanism of teat number traits in pigs. In this study, we detected Single Nucleotide Ploymorphism (SNP), Insertion-Deletion (InDel) and Structural variant (SV) by high-coverage whole-genome resequencing data, and selected teat number at birth and functional teat number as two types of teat number traits for genome-wide association study (GWAS) to reveal candidate genes associated with pig teat number traits.ResultsIn this study, we used whole genome resequencing data from 560 Yorkshire sows to detect SNPs, InDels and SVs, and performed GWAS for the traits of born teat number and functional teat number, and detected a total of 85 significant variants and screened 214 candidate genes, including HEG1, XYLT1, SULF1, MUC13, VRTN, RAP1A and NPVF. Among them, HEG1 and XYLT1 were the new candidate genes in this study. The co-screening and population validation of multiple traits suggested that HEG1 may have a critical effect on the born teat number.ConclusionOur study shows that more candidate genes associated with pig teat number traits can be identified by GWAS with different variant types. Through large population validation, we found that HEG1 may be a new key candidate gene affecting pig teat number traits. In conclusion, the results of this study provide new information for exploring the genetic mechanisms affecting pig teat number traits and genetic improvement of pigs.
Skeletal muscle is heterogeneous tissue, composed of fast-twitch fibers primarily relying on glycolysis and slow-twitch fibers primarily relying on oxidative phosphorylation. The relative expression and balance of glycolysis and oxidative phosphorylation in skeletal muscle are crucial for muscle growth and skeletal muscle metabolism. Here, we employed multi-omics approaches including transcriptomics, proteomics, phosphoproteomics, and metabolomics to unravel the role of circMYLK4, a differentially expressed circRNA in fast and slow-twitch muscle fibers, in muscle fiber metabolism. We discovered that circMYLK4 inhibits glycolysis and promotes mitochondrial oxidative phosphorylation. Mechanistically, circMYLK4 interacts with the voltage-gated calcium channel auxiliary subunit CACNA2D2, leading to the inhibition of Ca2+ release from the sarcoplasmic reticulum. The decrease in cytoplasmic Ca2+ concentration inhibits the expression of key enzymes, PHKB and PHKG1, involved in glycogen breakdown, thereby suppressing glycolysis. On the other hand, the increased fatty acid β-oxidation enhances the tricarboxylic acid cycle and mitochondrial oxidative phosphorylation. In general, circMYLK4 plays an indispensable role in maintaining the metabolic homeostasis of skeletal muscle.
Genomic prediction has been widely applied to the pig industry and has greatly accelerated the progress of genetic improvement in pigs. With the development of sequencing technology and price reduction, more and more genotype imputation panels of pig have been investigated, providing an effective and economical method to further study the genetic variation of pig economic traits. In this study, the imputation from 80 k Single Nucleotide Polymorphism chip data of 832 Large White pigs to whole-genome sequencing genotypes was performed by Swine Imputation Server, Pig Haplotypes Reference Panel (PHARP), Animal Genotype Imputation Database and 1k-pig-genomes four thousand-pig imputation panels. Then, linkage disequilibrium (LD) pruning and genome-wide association study (GWAS) preselected markers strategies were utilised to compare the genomic prediction accuracy of the different imputation data for reproductive traits, respectively. Our results showed that the PHARP panel exhibited the best genomic prediction accuracy among the four imputation panels. Meanwhile, the genomic prediction accuracy of the imputation data can be further improved by utilising the LD pruning and GWAS preselected marker strategies. In conclusion, our study provides insights into imputation data for pig genetic breeding.
The development of a comprehensive pig graph pangenome assembly encompassing 27 genomes represents the most extensive collection of pig genomic data to date. Analysis of this pangenome reveals the critical role of structural variations in driving adaptation and defining breed-specific traits. Notably, the study identifies BTF3 as a key candidate gene governing intramuscular fat deposition and meat quality in pigs. These findings underscore the power of pangenome approaches in uncovering novel genomic features underlying economically important agricultural traits. Collectively, these results demonstrate the value of leveraging large-scale, multi-genome analyses for advancing our understanding of livestock genomes and accelerating genetic improvement.
The quantity and distribution of fat deposits are crucial factors that impact the quality of pork. Recent studies have indicated that the utilization of natural ingredients plays a significant role in decreasing subcutaneous and visceral fat deposits, as well as enhancing intramuscular fat. Moreover, natural products possess several advantages including being environmentally friendly, safe, free of additives, and leaving no residue. Phenolic compounds derived from fruits, vegetables and herbs constitute of vital component of these natural ingredients. This article examines the influence of phenolic compounds on pig fat deposition, aiming to provide guidance on the utilization of such compounds to regulate fat deposition and enhance pork quality.
Understanding the porosity of biochar (BC) that promotes the heavy metal (HM) passivation during composting can contribute to the sustainable management of pig manure (PM). The current work aimed to explore the influence of BC with varying pore sizes on the physicochemical properties and morphological changes of HMs (including Zn, Cu, Cr, As, and Hg), and microbiota development during PM composting. The various pore sizes of BC were generated by pyrolyzing pine wood at 400 (T1), 500 (T2), 600 (T3) and 700 (T4) C, respectively. The results revealed a positive correlation between specific surface area of BC and pyrolysis temperature. BC addition contributed to a significantly extended compost warming rate and duration of high-temperature period, as well as HM passivation, reflected in the decrease in Exc-Zn (63-34%) and Red-Cu (28-13%) content, and the conversion of Oxi-Cr (29-21%) and Red-Hg (16-5%) to more stable forms. Moreover, BC at T4 exhibited the best effect on Zn and Cu passivation due to the highest specific surface area (380.03 m(2)/g). In addition to its impact on HM passivation, BC addition improved the microbial environment during PM composting, leading to enhanced microbial diversity and richness. Notably, Chloroflexi and Bacteroidota played key roles in promoting the transformation of Exc-Cu and Red-Hg into stable forms. This phenomenon further stimulated the enhanced decomposition of organic matter (OM) when BC prepared at 600-700 C-degrees was added. Therefore, it can be concluded that the regulation of BC porosity is an effective strategy to improve HM passivation and the overall effectiveness of PM composting.
Research on heavy metal passivation and nitrogen emissions is necessary for the pig industry. ● Mechanism of heavy metal passivation and nitrogen retention by different additives was introduced. ● Development and prospect of metal passivation, nitrogen preservation technology were discussed. The widespread use of feed additives in intensive and large-scale pig farming has resulted in high levels of heavy metals in pig manure. The long-term application of organic fertilizers containing high levels of heavy metals leads to the accumulation of heavy metals in the soil, which not only causes heavy metal pollution in the soil, and also affect food safety and endanger human health. Composting is an economical and effective technical measures to achieve environmentally-sustainable treatment of pig manure and is a practical method to reduce the problem of heavy metals and to improve the resource value of pig manure. The composting process is accompanied by high temperatures and the production and emission of gases, and also lead to changes in the nitrogen content of the compost and provide opportunity for heavy metal passivation additives. This paper summarizes the forms and types of heavy metals present in pig manure and reviews the progress of research as well as the techniques and problems of in the composting process, and provides recommendations for research on heavy metal passivation and nitrogen retention in pig manure composting.
BACKGROUND:Skeletal muscle is composed of muscle fibers with different physiological characteristics, which plays an important role in regulating skeletal muscle metabolism, movement and body homeostasis. The type of skeletal muscle fiber directly affects meat quality. However, the transcriptome and gene interactions between different types of muscle fibers are not well understood.RESULTS:In this paper, we selected 180-days-old Large White pigs and found that longissimus dorsi (LD) muscle was dominated by fast-fermenting myofibrils and soleus (SOL) muscle was dominated by slow-oxidizing myofibrils by frozen sections and related mRNA and protein assays. Here, we selected LD muscle and SOL muscle for transcriptomic sequencing, and identified 312 differentially expressed mRNA (DEmRs), 30 differentially expressed miRNA (DEmiRs), 183 differentially expressed lncRNA (DElRs), and 3417 differentially expressed circRNA (DEcRs). The ceRNA network included ssc-miR-378, ssc-miR-378b-3p, ssc-miR-24-3p, XR_308817, XR_308823, SMIM8, MAVS and FOS as multiple core nodes that play important roles in muscle development. Moreover, we found that different members of the miR-10 family expressed differently in oxidized and glycolytic muscle fibers, among which miR-10a-5p was highly expressed in glycolytic muscle fibers (LD) and could target MYBPH gene mRNA. Therefore, we speculate that miR-10a-5p may be involved in the transformation of muscle fiber types by targeting the MYHBP gene. In addition, PPI analysis of differentially expressed mRNA genes showed that ACTC1, ACTG2 and ACTN2 gene had the highest node degree, suggesting that this gene may play a key role in the regulatory network of muscle fiber type determination.CONCLUSIONS:We can conclude that these genes play a key role in regulating muscle fiber type transformation. Our study provides transcriptomic profiles and ceRNA interaction networks for different muscle fiber types in pigs, providing reference for the transformation of pig muscle fiber types and the improvement of meat quality.
The feeding mode is an important factor affecting the reproductive performance of pigs. The composition and expression of the intestinal microbiota are closely related to the physiological and biochemical indicators of animals. Therefore, to explore the impact of different feeding patterns on the reproductive performance of pigs, this study collected reproductive performance data from 1607 Yorkshire pigs raised under different feeding patterns and conducted a fixed-effect variance analysis. Among them, 731 were in the artificial feeding (AM) group and 876 were in the feeding station feeding (SM) group. Additionally, 40 Yorkshire sows in the late gestation period were randomly selected from each feeding mode for intestinal microbiota analysis. The results of the analysis showed that, in the AM group, both the number of birth deformities (NBD) and the number of stillbirths (NSB) were significantly greater than they were in the SM group (p < 0.05). Additionally, the total number born (TNB) in the AM group was significantly lower than that in the SM group (p < 0.05). The results of the intestinal microbiota analysis revealed that at the phylum level, there were significant differences in nine bacterial taxa between the AM and SM groups (p < 0.05). At the genus level, the abundance of a variety of beneficial bacteria related to reproductive performance in the SM group was significantly greater than that in the AM group. Finally, fecal metabolomic analysis revealed that the contents of butyric acid, isovaleric acid, valeric acid, and isobutyric acid, which are associated with reproductive performance, in the feces of sows in the SM group were significantly higher than those in the AM group (p < 0.05). These results indicate that different feeding methods can affect the gut microbiota composition of Yorkshire pigs and further influence the reproductive performance of pigs through the gut microbiota–metabolic product pathway. The results of this study provide valuable insights for further exploring the relationships between feeding modes, intestinal microbial composition, and host phenotypes.
Obesity has emerged as a major health risk on a global scale. Hinokiflavone (HF), a natural small molecule, extracted from plants like cypress, exhibits diverse chemical structures and low synthesis costs. Using high-fat diet-induced obese mice models, we found that HF suppresses obesity by inducing apoptosis in adipose tissue. Adipocyte apoptosis helps maintain tissue health by removing aging, damaged, or excess cells in adipose tissue, which is crucial in preventing obesity and metabolic diseases. We found that HF can specifically bind to insulin-like growth factor 2 mRNA binding protein 2 to promote the stability of N6-methyladenosine-modified Bim, inducing mitochondrial outer membrane permeabilization. Mitochondrial outer membrane permeabilization leads to Caspase9/3-mediated adipocyte mitochondrial apoptosis, alleviating obesity induced by a high-fat diet. The proapoptotic effect of HF offers a controlled means for weight loss. This study reveals the potential of small molecule HF in developing new therapeutic approaches in drug development and biomedical research.