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Impacts of the Callipyge mutation on ovine plasma metabolites and muscle fibre type.

Li J, Greenwood PL, Cockett NE, Hadfield TS, Vuocolo T, Byrne K, White JD, Tellam RL, Schirra HJ - PLoS ONE (2014)

Bottom Line: Using muscle fibre typing immunohistochemistry, we confirmed muscle specific effects and demonstrated that affected muscles had greater prevalence and hypertrophy of type 2X fast twitch glycolytic fibres and decreased representation of types 1, 2C, 2A and/or 2AX fibres.Microarray analysis of the perirenal adipose tissue depot did not reveal a transcriptional effect of the mutation in this tissue.We conclude that there is an indirect systemic effect of the Callipyge mutation in skeletal muscle in the form of changes of blood metabolites, which may contribute to secondary phenotypes such as body leanness.

View Article: PubMed Central - PubMed

Affiliation: CSIRO Animal, Food and Health Sciences, St Lucia, Brisbane, Australia.

ABSTRACT
The ovine Callipyge mutation causes postnatal muscle hypertrophy localized to the pelvic limbs and torso, as well as body leanness. The mechanism underpinning enhanced muscle mass is unclear, as is the systemic impact of the mutation. Using muscle fibre typing immunohistochemistry, we confirmed muscle specific effects and demonstrated that affected muscles had greater prevalence and hypertrophy of type 2X fast twitch glycolytic fibres and decreased representation of types 1, 2C, 2A and/or 2AX fibres. To investigate potential systemic effects of the mutation, proton NMR spectra of plasma taken from lambs at 8 and 12 weeks of age were measured. Multivariate statistical analysis of plasma metabolite profiles demonstrated effects of development and genotype but not gender. Plasma from Callipyge lambs at 12 weeks of age, but not 8 weeks, was characterized by a metabolic profile consistent with contributions from the affected hypertrophic fast twitch glycolytic muscle fibres. Microarray analysis of the perirenal adipose tissue depot did not reveal a transcriptional effect of the mutation in this tissue. We conclude that there is an indirect systemic effect of the Callipyge mutation in skeletal muscle in the form of changes of blood metabolites, which may contribute to secondary phenotypes such as body leanness.

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Orthogonal partial least squares – discriminant analysis (OPLS–DA) of lamb plasma metabolic profiles.Panel A: Scores plot of the comparison of plasma samples at 8 weeks (red dots) and 12 weeks (black dots) of age. Samples are separated by their age in dimension t[1], while the first orthogonal dimension to[1] contains orthogonal intra-group variation unrelated to age. Panel C: Scores plot of the comparison of plasma samples from NmatNpat (triangles) and NmatCpat (open triangles) lambs at 12 weeks of age. Samples are separated by genotype in dimension t[1], while the first orthogonal dimension to[1] contains intra-group variation unrelated to genotype. Panels B and D: corresponding 1D back-scaled loadings plots (0.5–5.1 ppm) for panels A and C, respectively, with the identity of several metabolites annotated. Weights of variables are shown by the colour scale. 3HB, 3-hydroxybutyrate; NAC, N-acetyl glycoproteins; TMAO, trimethylamine N-oxide; U3/U4, unknown metabolites 3/4.
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pone-0099726-g002: Orthogonal partial least squares – discriminant analysis (OPLS–DA) of lamb plasma metabolic profiles.Panel A: Scores plot of the comparison of plasma samples at 8 weeks (red dots) and 12 weeks (black dots) of age. Samples are separated by their age in dimension t[1], while the first orthogonal dimension to[1] contains orthogonal intra-group variation unrelated to age. Panel C: Scores plot of the comparison of plasma samples from NmatNpat (triangles) and NmatCpat (open triangles) lambs at 12 weeks of age. Samples are separated by genotype in dimension t[1], while the first orthogonal dimension to[1] contains intra-group variation unrelated to genotype. Panels B and D: corresponding 1D back-scaled loadings plots (0.5–5.1 ppm) for panels A and C, respectively, with the identity of several metabolites annotated. Weights of variables are shown by the colour scale. 3HB, 3-hydroxybutyrate; NAC, N-acetyl glycoproteins; TMAO, trimethylamine N-oxide; U3/U4, unknown metabolites 3/4.

Mentions: To investigate the effects of postnatal age on lamb metabolism, an OPLS–DA model was computed (n = 73, A: 1+3+0, R2X = 0.511, R2Y = 0.805, Q2 = 0.602, P(CV-ANOVA) = 2.33·10−10) from the 1D CPMG 1H NMR spectra of plasma samples (Figure 2A and 2B). Two sets of outputs, scores plots and loadings plots, were obtained from OPLS–DA analysis of 1H NMR spectra. Scores plots indicate the similarity of the metabolic profiles between samples. Each data point represents one NMR spectrum (sample) and clustering of points in the plots indicates that the respective samples have similar metabolite compositions. The loadings plots illustrate the metabolites responsible for the variation within the samples observed in the corresponding scores plot [52]. The effect of age on lamb plasma metabolites was illustrated by the clustering of the samples from each age in the scores plot (Figure 2A). Plasma samples from lambs at 8 and 12 weeks of age were separated in the first component (t[1]) of the OPLS–DA, which demonstrated that the metabolic profiles of lamb plasma changed between 8 and 12 weeks of age. The results from analysis of 1D NOESY spectra presented in the Supporting Information (Figure S4) are consistent with the results obtained from 1D CPMG spectra.


Impacts of the Callipyge mutation on ovine plasma metabolites and muscle fibre type.

Li J, Greenwood PL, Cockett NE, Hadfield TS, Vuocolo T, Byrne K, White JD, Tellam RL, Schirra HJ - PLoS ONE (2014)

Orthogonal partial least squares – discriminant analysis (OPLS–DA) of lamb plasma metabolic profiles.Panel A: Scores plot of the comparison of plasma samples at 8 weeks (red dots) and 12 weeks (black dots) of age. Samples are separated by their age in dimension t[1], while the first orthogonal dimension to[1] contains orthogonal intra-group variation unrelated to age. Panel C: Scores plot of the comparison of plasma samples from NmatNpat (triangles) and NmatCpat (open triangles) lambs at 12 weeks of age. Samples are separated by genotype in dimension t[1], while the first orthogonal dimension to[1] contains intra-group variation unrelated to genotype. Panels B and D: corresponding 1D back-scaled loadings plots (0.5–5.1 ppm) for panels A and C, respectively, with the identity of several metabolites annotated. Weights of variables are shown by the colour scale. 3HB, 3-hydroxybutyrate; NAC, N-acetyl glycoproteins; TMAO, trimethylamine N-oxide; U3/U4, unknown metabolites 3/4.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4061035&req=5

pone-0099726-g002: Orthogonal partial least squares – discriminant analysis (OPLS–DA) of lamb plasma metabolic profiles.Panel A: Scores plot of the comparison of plasma samples at 8 weeks (red dots) and 12 weeks (black dots) of age. Samples are separated by their age in dimension t[1], while the first orthogonal dimension to[1] contains orthogonal intra-group variation unrelated to age. Panel C: Scores plot of the comparison of plasma samples from NmatNpat (triangles) and NmatCpat (open triangles) lambs at 12 weeks of age. Samples are separated by genotype in dimension t[1], while the first orthogonal dimension to[1] contains intra-group variation unrelated to genotype. Panels B and D: corresponding 1D back-scaled loadings plots (0.5–5.1 ppm) for panels A and C, respectively, with the identity of several metabolites annotated. Weights of variables are shown by the colour scale. 3HB, 3-hydroxybutyrate; NAC, N-acetyl glycoproteins; TMAO, trimethylamine N-oxide; U3/U4, unknown metabolites 3/4.
Mentions: To investigate the effects of postnatal age on lamb metabolism, an OPLS–DA model was computed (n = 73, A: 1+3+0, R2X = 0.511, R2Y = 0.805, Q2 = 0.602, P(CV-ANOVA) = 2.33·10−10) from the 1D CPMG 1H NMR spectra of plasma samples (Figure 2A and 2B). Two sets of outputs, scores plots and loadings plots, were obtained from OPLS–DA analysis of 1H NMR spectra. Scores plots indicate the similarity of the metabolic profiles between samples. Each data point represents one NMR spectrum (sample) and clustering of points in the plots indicates that the respective samples have similar metabolite compositions. The loadings plots illustrate the metabolites responsible for the variation within the samples observed in the corresponding scores plot [52]. The effect of age on lamb plasma metabolites was illustrated by the clustering of the samples from each age in the scores plot (Figure 2A). Plasma samples from lambs at 8 and 12 weeks of age were separated in the first component (t[1]) of the OPLS–DA, which demonstrated that the metabolic profiles of lamb plasma changed between 8 and 12 weeks of age. The results from analysis of 1D NOESY spectra presented in the Supporting Information (Figure S4) are consistent with the results obtained from 1D CPMG spectra.

Bottom Line: Using muscle fibre typing immunohistochemistry, we confirmed muscle specific effects and demonstrated that affected muscles had greater prevalence and hypertrophy of type 2X fast twitch glycolytic fibres and decreased representation of types 1, 2C, 2A and/or 2AX fibres.Microarray analysis of the perirenal adipose tissue depot did not reveal a transcriptional effect of the mutation in this tissue.We conclude that there is an indirect systemic effect of the Callipyge mutation in skeletal muscle in the form of changes of blood metabolites, which may contribute to secondary phenotypes such as body leanness.

View Article: PubMed Central - PubMed

Affiliation: CSIRO Animal, Food and Health Sciences, St Lucia, Brisbane, Australia.

ABSTRACT
The ovine Callipyge mutation causes postnatal muscle hypertrophy localized to the pelvic limbs and torso, as well as body leanness. The mechanism underpinning enhanced muscle mass is unclear, as is the systemic impact of the mutation. Using muscle fibre typing immunohistochemistry, we confirmed muscle specific effects and demonstrated that affected muscles had greater prevalence and hypertrophy of type 2X fast twitch glycolytic fibres and decreased representation of types 1, 2C, 2A and/or 2AX fibres. To investigate potential systemic effects of the mutation, proton NMR spectra of plasma taken from lambs at 8 and 12 weeks of age were measured. Multivariate statistical analysis of plasma metabolite profiles demonstrated effects of development and genotype but not gender. Plasma from Callipyge lambs at 12 weeks of age, but not 8 weeks, was characterized by a metabolic profile consistent with contributions from the affected hypertrophic fast twitch glycolytic muscle fibres. Microarray analysis of the perirenal adipose tissue depot did not reveal a transcriptional effect of the mutation in this tissue. We conclude that there is an indirect systemic effect of the Callipyge mutation in skeletal muscle in the form of changes of blood metabolites, which may contribute to secondary phenotypes such as body leanness.

Show MeSH
Related in: MedlinePlus