MiR-F4-C12 Functions on the Regulation of Adipose Accumulation by Targeting PIK3R1 in Castrated Male Pigs.
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ABSTRACT:
SUBMITTER: Xu Q
PROVIDER: S-EPMC8614499 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Castration of male pigs is a common practice used to reduce boar taint in commercial pork production, but it also significantly results in fat accumulation in carcass. Our previous study revealed a miRNA gene, ssc-miR-7134-3p that was implicated in adipogenesis. However, the relationship between ssc-miR-7134-3p and fat deposition due to castration is unknown. In the present study, we observed that ssc-miR-7134-3p targets the coding sequence (CDS) region of MARK4 based on bioinformatics analysis and dual-luciferase assays. Experiments using silent mutations and sub-cloning showed that ssc-miR-7134-3p binds independently to two adjacent sites in the MARK4 CDS. Subsequently, ssc-miR-7134-3p inhibits MARK4 protein expression in pig fibroblast cells, being consistent with the targeting demonstrated in vitro. We found higher MARK4 protein levels in the back fat of castrated pigs than in intact pigs, providing further evidence that MARK4 is involved in regulation of fat deposition. In addition, one SNP (g.2581A>G) in MARK4 was significantly associated with the back fat trait in Chinese and European pig populations. Taken together, we would conclude that ssc-miR-7134-3p targets the MARK4 gene for fat accumulation in the castrated male pigs.
| S-EPMC5332873 | biostudies-other
Project description:Differences in adipose tissue deposition and properties between pig male sex categories, i.e., entire males (EM), immunocastrates (IC) and surgical castrates (SC) are relatively well-characterized, whereas the underlying molecular mechanisms are still not fully understood. To gain knowledge about the genetic regulation of the differences in adipose tissue deposition, two different approaches were used: RNA-sequencing and candidate gene expression by quantitative PCR. A total of 83 differentially expressed genes were identified between EM and IC, 15 between IC and SC and 48 between EM and SC by RNA-sequencing of the subcutaneous adipose tissue. Comparing EM with IC or SC, upregulated genes related to extracellular matrix dynamics and adipogenesis, and downregulated genes involved in the control of lipid and carbohydrate metabolism were detected. Differential gene expression generally indicated high similarity between IC and SC as opposed to EM, except for several heat shock protein genes that were upregulated in EM and IC compared with SC. The candidate gene expression approach showed that genes involved in lipogenesis were downregulated in EM compared with IC pigs, further confirming RNA-sequencing results.
| S-EPMC7916650 | biostudies-literature
Project description:Castration is usually used to remove boar taint in commercial pork production, but the adipose accumulation was increased excessively, which affected the meat quality of pigs. Based on our previous study, secreted phosphoprotein 1 (SPP1) was significantly differentially expressed between castrated and intact male pigs. However, the role of SPP1 in regulating adipose growth and fat storage caused by castration is unknown. In this study, SPP1 was identified to inhibit adipogenesis by the expression of adipogenic markers PPARγ and FABP4 as well as Oil red staining assay during differentiation of porcine bone marrow mesenchymal stem cells (pBMSCs). Subsequently, testosterone was used to treat pBMSCs to simulate the androgen status of intact pigs. Compared with the control groups without testosterone, the SPP1 expression in the testosterone group was markedly increased in the late stage of pBMSCs differentiation. Furthermore, novel-miR-659 was predicted by TargetScan and miRDB to target SPP1 and verified through a dual-luciferase reporter assay. Oil Red O staining assay indicated that novel-miR-659 overexpression significantly promoted adipogenesis, whereas novel-miR-659 inhibition suppressed adipogenesis. The expressions of adipogenic markers PPARγ and FABP4 showed the same tendency. Taken together, our study found that the targeted interaction between novel-miR-659 and SPP1 is involved in regulation of fat deposition in castrated male pigs.
| S-EPMC9031235 | biostudies-literature
Project description:BackgroundLong non-coding RNAs (lncRNAs) regulate adipose tissue metabolism, however, their function on testosterone deficiency related obesity in humans is less understood. For this research, intact and castrated male pigs are the best model animal because of their similar proportional organ sizes, cardiovascular systems and metabolic features.ResultsWe identified lncRNAs in subcutaneous adipose tissue by deep RNA-sequencing using the intact and castrated Huainan male pigs. The results showed that castration reduced serum testosterone but increased body fatness-related traits (serum triglyceride levels, backfat thickness, intramuscular fat content, and adipocyte size). Meanwhile, 343 lncRNAs from subcutaneous adipose tissue were identified, including 223 intergenic lncRNAs (lincRNAs), 68 anti-sense lncRNAs, and 52 intronic lncRNAs. It was predicted that there were 416 recognition sites for C/EBPα in the 303 lncRNA promoter region, and 13 adipogenesis-promoting miRNAs and five adipogenesis-depressing miRNAs target these lncRNAs. Eighteen lncRNAs, including nine up- and nine down-regulated had more than 2-fold differential expression between the castrated and intact male pigs (q-value < 0.05). Functional analysis indicated that these 18 lncRNAs and their target genes were involved in fatty acid, insulin, and the adipocytokine signaling pathway. We further analyzed the features of a conserved mouse lncRNA gene ENSMUST00000189966 and found it mainly expressed in the cell nucleus and target the Nuclear Receptor Subfamily 2 Group F Member 2 (NR2F2) gene. In 3 T3-L1 cells, differentiation down-regulated their expression, but dihydrotestosterone (DHT) significantly up-regulated their expression in a concentration-dependent manner (P < 0.05).ConclusionsThese results suggested that lncRNAs and their target genes might participated in the castration-induced fat deposition and provide a new therapeutic target for combatting testosterone deficiency-related obesity.
| S-EPMC5518130 | biostudies-literature
Project description:CircRNAs play an important role in fat deposition, and testosterone-deficient boars exhibit significantly increased fat deposition; however, the mechanism by which testosterone regulates fat deposition through circRNAs remains unclear. In this study, circRNA-seq of backfat and abdominal fat from castrated and intact full-sib Yorkshire pigs was performed. The GO and KEGG enrichment analyses revealed that the host genes of the dorsal DE circRNAs were mainly involved in fatty acid transport, while in abdominal tissues, these genes were mainly involved in adipogenesis and inflammation. The interaction among sus_circPAPPA2, ssc-miR-2366 and GK was verified by dual fluorescence experiments and in porcine preadipocytes. The overexpression of sus_circPAPPA2 significantly inhibited the differentiation of preadipocytes. The expression of sus_circPAPPA2 was increased after adding 100 nM of testosterone, and preadipocyte differentiation was significantly inhibited. Testosterone can affect preadipocyte differentiation by upregulating the expression of sus_circPAPPA2, sponging miR-2366 and regulating the expression of genes, such as GK. These results indicate that testosterone can regulate the expression of adipocyte differentiation- and lipid metabolism-related genes by regulating the expression of circRNA, and ceRNA networks are different in the testosterone regulation of adipose deposition in different parts. This study provides basic data enhancing the understanding of the interaction between the hormone environment and mir-2366/GK to regulate trait performance in pigs.
| S-EPMC9220968 | biostudies-literature
Project description:Differences in adipose tissue deposition and properties between pig male sex categories, i.e., entire male, immunocastrated and surgically castrated pigs are relatively well characterized, whereas the underlying genetic mechanisms are still not fully understood. To gain the knowledge about the genetic regulation of the differences in adipose tissue deposition, RNA-sequencing approach was used. A total of 83 differentially expressed genes were identified between entire male and immunocastrated pigs, 15 between immunocastrated and surgically castrated pigs and 48 between entire male and surgically castrated pigs by RNA-sequencing of the subcutaneous adipose tissue. Comparing entire male with immunocastrated or surgically castrated pigs, upregulated genes related to extracellular matrix dynamics, and downregulated genes involved in the control of lipid and carbohydrate metabolism were determinated. Moreover, differential gene expression in general indicated a high similarity between immunocastrated and surgically castrated pigs in contrast to entire males, except for several heat shock protein genes which were upregulated in entire male and immunocastrated pigs compared with surgically castrated pigs.
2021-03-03 | GSE164391 | GEO
Project description:There are indications of reduced meat quality in entire male pigs (EMs) in comparison to surgically castrated pigs (SCs); however, the differences are not strongly confirmed, and the etiology is not clarified. In the present study, samples of the longissimus dorsi, pars lumborum muscle (LL) from EMs (n = 12) and SCs (n = 12) of the same age and weight were evaluated at the physico-chemical and proteomic level. EMs exhibited lower intramuscular fat content, higher collagen content with higher solubility, a higher level of protein carbonyl groups (indicating higher protein oxidation), lower water holding capacity, and tougher meat than SCs. Proteomic analysis revealed differences in heat shock proteins expression, while a greater abundance of several other identified proteins (malate dehydrogenase, Na/K-transporting adenosintriphosphatase (ATP-ase) subunit alpha-1, and blood plasma proteins) indicates that EMs have a more oxidative metabolic profile than that of SCs. More abundant protein fragments (mainly actin and myosin heavy chain) suggest a higher degree of proteolysis in EMs, which was not followed by lower meat toughness.
| S-EPMC6465998 | biostudies-literature
Project description:BACKGROUND: It is widely known that castration has a significant effect on the accumulation of adipose tissue. microRNAs (miRNAs) are known to be involved in fat deposition and to be regulated by the androgen-induced androgen receptor (AR). However, there is little understanding of the relationship between miRNAs and fat deposition after castration. In this study, the high-throughput SOLiD sequencing approach was used to identify and characterize miRNA expression in backfat from intact and castrated full-sib male 23-week-old pigs. The patterns of adipogenesis and fat deposition were compared between castrated and intact male pigs. RESULTS: A total of 366 unique miRNA genes were identified, comprising 174 known pre-miRNAs and 192 novel pre-miRNAs. One hundred and sixty-seven pre-miRNAs were common to both castrated (F3) and intact (F4) male pig small RNA libraries. The novel pre-miRNAs encoded 153 miRNAs/miRNA*s and 141 miRNAs/miRNA*s in the F3 and F4 libraries, respectively. One hundred and seventy-seven miRNAs, including 45 up- and 132 down-regulated, had more than 2-fold differential expression between the castrated and intact male pigs (p-value < 0.001). Thirty-five miRNAs were further selected, based on the expression abundance and differentiation between the two libraries, to predict their targets in KEGG pathways. KEGG pathway analyses suggested that miRNAs differentially expressed between the castrated and intact male pigs are involved in proliferation, apoptosis, differentiation, migration, adipose tissue development and other important biological processes. The expression patterns of eight arbitrarily selected miRNAs were validated by stem-loop reverse-transcription quantitative polymerase chain reaction. These data confirmed the expression tendency observed with SOLiD sequencing. miRNA isomiRs and mirtrons were also investigated in this study. Mirtrons are a recently described category of miRNA relying on splicing rather than processing by the microprocessor complex to generate the RNAi pathway. The functions of miRNAs important for regulating fat deposition were also investigated in this study. CONCLUSIONS: This study expands the number of fat-deposition-related miRNAs in pig. The results also indicate that castration can significantly affect the expression patterns of fat-related miRNAs. The differentially expressed miRNAs may play important roles in fat deposition after castration.
| S-EPMC3901342 | biostudies-other
Project description:BackgroundBrain and immune system are linked in a bi-directional manner. To date, it remained largely unknown why immune components become suppressed, enhanced, or remain unaffected in relation to psychosocial stress. Therefore, we mixed unfamiliar pigs with different levels of aggressiveness. We separated castrated male and female pigs into psychosocially high- and low- stressed animals by skin lesions, plasma cortisol level, and creatine kinase activity obtained from agonistic behaviour associated with regrouping. Peripheral blood mononuclear cells (PBMC) were collected post-mortem and differential gene expression was assessed using the Affymetrix platform (n = 16).ResultsRelevant stress-dependent alterations were found only between female samples, but not between castrated male samples. Molecular routes related to TREM 1 signalling, dendritic cell maturation, IL-6 signalling, Toll-like receptor signalling, and IL-8 signalling were increased in high stressed females compared to low stressed females. This indicates a launch of immune effector molecules as a direct response. According to the shifts of transcripts encoding cell surface receptors (e.g. CD14, TLR2, TLR4, TREM1) the study highlights processes acting on pattern recognition, inflammation, and cell-cell communication.ConclusionsThe transcriptional response partly affected the degree of 'stress responsiveness', indicating that the high stressed females altered their signal transduction due to potential infections and injuries while fighting.
| S-EPMC4233077 | biostudies-literature
Project description:BackgroundExcessive backfat deposition lowering carcass grade is a major concern in the pig industry, especially in most breeds of obese type pigs. The mechanisms involved in adipogenesis and fat accumulation in pigs remain unclear. Lysine 2-hydroxyisobutyrylation (Khib), is a novel protein post-translational modification (PTM), which play an important role in transcription, energy metabolism and metastasis of cancer cells, but its role in adipogenesis and fat accumulation has not been shown.ResultsIn this study, we first analyzed the modification levels of acetylation (Kac), Khib, crotonylation (Kcr) and succinylation (Ksu) of fibro-adipogenic progenitors (FAPs), myogenic precursors (Myo) and mesenchymal stem cells (MSCs) with varied differentiation potential, and found that only Khib modification in FAPs was significantly higher than that in MSCs. Consistently, in parallel with its regulatory enzymes lysine acetyltransferase 5 (KAT5) and histone deacetylase 2 (HDAC2) protein levels, the Khib levels increased quadratically (P < 0.01) during adipogenic differentiation of FAPs. KAT5 knockdown in FAPs inhibited adipogenic differentiation, while HDAC2 knockdown enhanced adipogenic differentiation. We also demonstrated that Khib modification favored to adipogenic differentiation and fat accumulation by comparing Khib levels in FAPs and backfat tissues both derived from obese-type pigs (Laiwu pigs) and lean-type pigs (Duroc pigs), respectively. Accordingly, the expression patterns of KAT5 and HDAC2 matched well to the degree of backfat accumulation in obese- and lean-type pigs.ConclusionsFrom the perspective of protein translational modification, we are the first to reveal the role of Khib in adipogenesis and fat deposition in pigs, and provided new clues for the improvement of fat accumulation and distribution as expected via genetic selection and nutritional strategy in obese-type pigs.
| S-EPMC11242017 | biostudies-literature