A Systems Biology Approach Using Transcriptomic Data Reveals Genes and Pathways in Porcine Skeletal Muscle Affected by Dietary Lysine

Abstract

Nine crossbred finishing barrows (body weight 94.4 ± 6.7 kg) randomly assigned to three dietary treatments were used to investigate the effects of dietary lysine on muscle growth related metabolic and signaling pathways. Muscle samples were collected from the longissimus dorsi of individual pigs after feeding the lysine-deficient (4.30 g/kg), lysine-adequate (7.10 g/kg), or lysine-excess (9.80 g/kg) diet for five weeks, and the total RNA was extracted afterwards. Affymetrix Porcine Gene 1.0 ST Array was used to quantify the expression levels of 19,211 genes. Statistical ANOVA analysis of the microarray data showed that 674 transcripts were differentially expressed (at p ≤ 0.05 level); 60 out of 131 transcripts (at p ≤ 0.01 level) were annotated in the NetAffx database. Ingenuity pathway analysis showed that dietary lysine deficiency may lead to: (1) increased muscle protein degradation via the ubiquitination pathway as indicated by the up-regulated DNAJA1, HSP90AB1 and UBE2B mRNA; (2) reduced muscle protein synthesis via the up-regulated RND3 and ZIC1 mRNA; (3) increased serine and glycine synthesis via the up-regulated PHGDH and PSPH mRNA; and (4) increased lipid accumulation via the up-regulated ME1, SCD, and CIDEC mRNA. Dietary lysine excess may lead to: (1) decreased muscle protein degradation via the down-regulated DNAJA1, HSP90AA1, HSPH1, and UBE2D3 mRNA; and (2) reduced lipid biosynthesis via the down-regulated CFD and ME1 mRNA. Collectively, dietary lysine may function as a signaling molecule to regulate protein turnover and lipid metabolism in the skeletal muscle of finishing pigs.

Effects of dietary lysine level on the content and fatty acid composition of intramuscular fat in late-stage finishing pigs

“…This result regarding the SCD activity is supported by da Costa et al (2004) and Doran et al (2006), who found that the levels of SCD mRNA and protein expression were increased in porcine skeletal muscle when the levels of dietary crude protein and lysine were low. In our previous report concerning the muscle gene expression in these pigs (Wang et al 2017), we also found that Diet 1 (i.e., the lysine-deficient diet) significantly increased (P < 0.05) the mRNA abundance of the SCD gene.…”

“…As suggested by the SCD gene expression data (Wang et al 2017), together with the IMF content and FA composition data obtained from this study, it seems that a greater activity of adipogenesis might be the reason for the increased IMF content in pigs fed the lysine-deficient diet. The SCD activity indices reported here reflected the SCD gene expression data on the same animals (Wang et al 2017), and further indicate that SCD might be a critical enzyme for regulation of FA biosynthesis and IMF content in these pigs.…”

“…Related to lipid metabolism in skeletal muscle, SCD enzyme catalyzes the conversion of SFA (primarily C16:0 and C18:0) to the corresponding MUFA (such as C16:1 and C18:1), and has been shown to be associated with the IMF formation in pigs (da Costa et al 2004;Doran et al 2006;Bessa et al 2013). As suggested by the SCD gene expression data (Wang et al 2017), together with the IMF content and FA composition data obtained from this study, it seems that a greater activity of adipogenesis might be the reason for the increased IMF content in pigs fed the lysine-deficient diet. The SCD activity indices reported here reflected the SCD gene expression data on the same animals (Wang et al 2017), and further indicate that SCD might be a critical enzyme for regulation of FA biosynthesis and IMF content in these pigs.…”

“…In our previous study, dietary lysine affected the expression of several key genes, such as the gene encoding stearoyl-CoA desaturase (SCD; EC 1.14.19.1) that is related to FA synthesis in skeletal muscle (Wang et al 2017). Catalyzing a rate-limiting step in the conversion of SFA to the corresponding MUFA, SCD plays a key role in altering IMF composition in pigs (da Costa et al 2004;Doran et al 2006;Bessa et al 2013).…”

Genome‐wide DNA methylation and transcription analysis in tongue and biceps femoris muscles of cloned pigs with macroglossia

“…Increased activity of this enzyme in infants with hemangiomas causes severe hypothyroidism (Huang et al 2000), an endocrine disorder sometimes accompanied by the phenotype of macroglossia (Sonal & Bhavin 2014). ZIC1 plays a key role in the development of the cerebellum, and a previous study showed that ZIC1 mRNA expression was up-regulated by lysine-deficiency and this might suppress protein synthesis in porcine muscle (Wang et al 2017). It is not clear whether the suppressed expression of ZIC1 observed in our study did promote muscle protein synthesis and cause excessive hyperplasia of the tongue muscle.…”