ABSTRACT: Local crosstalk between the lipid deposition and skeletal muscle growth inhibition from Bama minipig obesity model by high-fat high-sucrose diet
Project description:The underlying mechanism of how the atopic lipids in skeletal muscle affect muscle growth remains elusive. Here we chose miniature Bama swine as our model to mimick human obesity and co-associated metabolic disorders by long time diet induction and study how the atopic fat accumulation in skeletal muscle influence muscle function. After 23 months high-fat high-sucrose diet (HFHSD) fed, the model minipig model of obesity accompanied with metabolic disorders like human, and they had increased body weight and extensive lipids deposition in adipose tissues (AT) and non-AT, especially in skeletal muscle. Further more, the mass of skeletal reduced greatly and the small area (0-2000μm2) muscle reduced after diet induced. The average fiber area of Gastroc reduced 25.2%, but no significant changes appeared in the other skeletal muscles. Antioxidant capacity of skeletal muscle also reduced. Microarray profiles showed genes related to fat deposition promotion (Peroxisome proliferator activated receptor γ, CCAAT/enhancer-binding protein α and apolipoprotein E), muscle growth inhibition (myostatin and p21) up regulated, and some other muscle cell differentiation related genes (myoD) down regulated. Meanwhile, adipokines like adiponectin and 11b-hydroxysteroid dehydrogenase type 1 (11βHSD1) which partake in the crosstalk between AT and skeletal muscles rose up. We draw a clear potential crosstalk pathway that, increased 11βHSD1 secreted by excess AT will promote the expression of the major inhibitor MSTN by activating corticosterone to cortisol, leading to the growth inhibition of skeletal muscle. Overall, this research announces how obesity affects skeletal muscle growth in a crosstalk sight. Male and female Bama minipigs, aged 6 months at the start of the study, were divided into the following two groups for 23 months of treatment. Bama minipigon control (CD group, N=3) were fed standard pig chow. The experimental group (N=6) were fed high-fat high-sucrose diet (53% basal diet, 37% sucrose, 10% lard, HFHSD).
Project description:The underlying mechanism of how the atopic lipids in skeletal muscle affect muscle growth remains elusive. Here we chose miniature Bama swine as our model to mimick human obesity and co-associated metabolic disorders by long time diet induction and study how the atopic fat accumulation in skeletal muscle influence muscle function. After 23 months high-fat high-sucrose diet (HFHSD) fed, the model minipig model of obesity accompanied with metabolic disorders like human, and they had increased body weight and extensive lipids deposition in adipose tissues (AT) and non-AT, especially in skeletal muscle. Further more, the mass of skeletal reduced greatly and the small area (0-2000μm2) muscle reduced after diet induced. The average fiber area of Gastroc reduced 25.2%, but no significant changes appeared in the other skeletal muscles. Antioxidant capacity of skeletal muscle also reduced. Microarray profiles showed genes related to fat deposition promotion (Peroxisome proliferator activated receptor γ, CCAAT/enhancer-binding protein α and apolipoprotein E), muscle growth inhibition (myostatin and p21) up regulated, and some other muscle cell differentiation related genes (myoD) down regulated. Meanwhile, adipokines like adiponectin and 11b-hydroxysteroid dehydrogenase type 1 (11βHSD1) which partake in the crosstalk between AT and skeletal muscles rose up. We draw a clear potential crosstalk pathway that, increased 11βHSD1 secreted by excess AT will promote the expression of the major inhibitor MSTN by activating corticosterone to cortisol, leading to the growth inhibition of skeletal muscle. Overall, this research announces how obesity affects skeletal muscle growth in a crosstalk sight.
Project description:The anterior pituitary is the most important endocrine organ modulating animal postnatal growth, mainly by controlling growth hormone (GH) gene transcription, synthesis, and secretion. As an ideal model for animal postnatal growth studies, the Bama minipig is characterized as having a lower growth performance and fewer individual differences compared with larger pig breeds. In this study, anterior pituitaries from Bama minipig and Landrace pig were used for miRNA and mRNA expression profile analysis using miRNA microarrays and mRNA-seq. Consequently, a total of 222 miRNAs and 12,909 transcripts were detected, and both miRNAs and mRNAs in the two breeds showed high correlation (r > 0.97). Additionally, 41 differentially expressed miRNAs and 2,254 transcripts were identified. Pathways analysis indicated that 32 pathways significantly differed in the two breeds. Importantly, two GH-regulation-signalling pathways, cAMP and inositol 1, 4, 5-triphosphate (IP3), and multiple GH-secretion-related transcripts were significantly down-regulated in Bama minipigs. Moreover, target prediction by two algorithms (TargetScan and RNAhybrid) indicated that most miRNA–mRNA target pairs (63.68–71.33%) presented a negatively correlated expression pattern. A possible network among miRNAs, mRNAs, and GH-regulation pathways was also proposed. These data will be helpful in understanding the possible molecular mechanisms involved in animal postnatal growth. 2 pooled samples were analyzed. A pool of 3 pig anterior pituitary was used for Bama minpigs and Landrace pigs,respectively.
Project description:The anterior pituitary is the most important endocrine organ modulating animal postnatal growth, mainly by controlling growth hormone (GH) gene transcription, synthesis, and secretion. As an ideal model for animal postnatal growth studies, the Bama minipig is characterized as having a lower growth performance and fewer individual differences compared with larger pig breeds. In this study, anterior pituitaries from Bama minipig and Landrace pig were used for miRNA and mRNA expression profile analysis using miRNA microarrays and mRNA-seq. Consequently, a total of 222 miRNAs and 12,909 transcripts were detected, and both miRNAs and mRNAs in the two breeds showed high correlation (r > 0.97). Additionally, 41 differentially expressed miRNAs and 2,254 transcripts were identified. Pathways analysis indicated that 32 pathways significantly differed in the two breeds. Importantly, two GH-regulation-signalling pathways, cAMP and inositol 1, 4, 5-triphosphate (IP3), and multiple GH-secretion-related transcripts were significantly down-regulated in Bama minipigs. Moreover, target prediction by two algorithms (TargetScan and RNAhybrid) indicated that most miRNA–mRNA target pairs (63.68–71.33%) presented a negatively correlated expression pattern. A possible network among miRNAs, mRNAs, and GH-regulation pathways was also proposed. These data will be helpful in understanding the possible molecular mechanisms involved in animal postnatal growth. mRNA profiling in the anterior pituitary from two different pig breeds.2 pooled samples were analyzed. A pool of 3 pig anterior pituitary was used for Bama minpigs(YB) and Landrace pigs(YC),respectively.
Project description:Deep cutaneous injuries in adult mammals often lead to fibrotic scarring, a process exacerbated by inflammatory fibroblasts that amplify immune recruitment. Early modulation of immune-fibroblast crosstalk represents a promising therapeutic strategy. Here we show that GAS6 is a key regulator of this interaction and can be therapeutically targeted using a spatiotemporally controlled lipid nanoparticle (LNP)-mRNA hydrogel platform. We engineer LNP-GAS6 mRNA to enhance macrophage efferocytosis and suppress inflammatory fibroblasts, then encapsulate it in a thermosensitive hydrogel for localized delivery. In murine, rabbit ear, and Bama minipig wound models, this treatment significantly accelerates wound closure and reduces fibrotic scarring. These results demonstrate that restoring GAS6 signaling via mRNA-based delivery promotes scarless healing and offers an effective therapeutic approach for fibrotic skin disorders.
Project description:Minipigs are animal models widely used in biomedical studies due to their physiological and anatomical similarities to humans. However, a comprehensive resource for the Korean minipig (Sus scrofa) transcriptome remains unavailable. In this study, we constructed a de novo transcriptome of the Korean minipig using RNA-seq data obtained from ten tissues across ten samples. The final assembly comprised 57,085 coding transcripts with an average length of 3,075 nucleotides and an N50 of 4,258 nucleotides. In total, 65.4% of the transcripts were annotated, and biological functions were assigned. Transcript expression profiling and principal component analysis showed that samples clustered by tissue type, reflecting transcriptomic features shared across tissues. Comparative analysis demonstrated that the novel transcriptome assembly had contiguity and completeness comparable to those available for pig and minipig breeds. Overall, this study provides a comprehensive transcriptomic resource for the Korean minipig, facilitating further functional analyses.
Project description:Minipigs are animal models widely used in biomedical studies due to their physiological and anatomical similarities to humans. However, a comprehensive resource for the Korean minipig (Sus scrofa) transcriptome remains unavailable. In this study, we constructed a de novo transcriptome of the Korean minipig using RNA-seq data obtained from ten tissues across ten samples. The final assembly comprised 57,085 coding transcripts with an average length of 3,075 nucleotides and an N50 of 4,258 nucleotides. In total, 65.4% of the transcripts were annotated, and biological functions were assigned. Transcript expression profiling and principal component analysis showed that samples clustered by tissue type, reflecting transcriptomic features shared across tissues. Comparative analysis demonstrated that the novel transcriptome assembly had contiguity and completeness comparable to those available for pig and minipig breeds. Overall, this study provides a comprehensive transcriptomic resource for the Korean minipig, facilitating further functional analyses.
Project description:The anterior pituitary is the most important endocrine organ modulating animal postnatal growth, mainly by controlling growth hormone (GH) gene transcription, synthesis, and secretion. As an ideal model for animal postnatal growth studies, the Bama minipig is characterized as having a lower growth performance and fewer individual differences compared with larger pig breeds. In this study, anterior pituitaries from Bama minipig and Landrace pig were used for miRNA and mRNA expression profile analysis using miRNA microarrays and mRNA-seq. Consequently, a total of 222 miRNAs and 12,909 transcripts were detected, and both miRNAs and mRNAs in the two breeds showed high correlation (r > 0.97). Additionally, 41 differentially expressed miRNAs and 2,254 transcripts were identified. Pathways analysis indicated that 32 pathways significantly differed in the two breeds. Importantly, two GH-regulation-signalling pathways, cAMP and inositol 1, 4, 5-triphosphate (IP3), and multiple GH-secretion-related transcripts were significantly down-regulated in Bama minipigs. Moreover, target prediction by two algorithms (TargetScan and RNAhybrid) indicated that most miRNA–mRNA target pairs (63.68–71.33%) presented a negatively correlated expression pattern. A possible network among miRNAs, mRNAs, and GH-regulation pathways was also proposed. These data will be helpful in understanding the possible molecular mechanisms involved in animal postnatal growth.
Project description:The anterior pituitary is the most important endocrine organ modulating animal postnatal growth, mainly by controlling growth hormone (GH) gene transcription, synthesis, and secretion. As an ideal model for animal postnatal growth studies, the Bama minipig is characterized as having a lower growth performance and fewer individual differences compared with larger pig breeds. In this study, anterior pituitaries from Bama minipig and Landrace pig were used for miRNA and mRNA expression profile analysis using miRNA microarrays and mRNA-seq. Consequently, a total of 222 miRNAs and 12,909 transcripts were detected, and both miRNAs and mRNAs in the two breeds showed high correlation (r > 0.97). Additionally, 41 differentially expressed miRNAs and 2,254 transcripts were identified. Pathways analysis indicated that 32 pathways significantly differed in the two breeds. Importantly, two GH-regulation-signalling pathways, cAMP and inositol 1, 4, 5-triphosphate (IP3), and multiple GH-secretion-related transcripts were significantly down-regulated in Bama minipigs. Moreover, target prediction by two algorithms (TargetScan and RNAhybrid) indicated that most miRNA–mRNA target pairs (63.68–71.33%) presented a negatively correlated expression pattern. A possible network among miRNAs, mRNAs, and GH-regulation pathways was also proposed. These data will be helpful in understanding the possible molecular mechanisms involved in animal postnatal growth.