Dataset Information

Lower Expression of SLC27A1 Enhances Intramuscular Fat Deposition in Chicken via Down-Regulated Fatty Acid Oxidation Mediated by CPT1A.

ABSTRACT: Intramuscular fat (IMF) is recognized as the predominant factor affecting meat quality due to its positive correlation with tenderness, juiciness, and flavor. Chicken IMF deposition depends on the balance among lipid synthesis, transport, uptake, and subsequent metabolism, involving a lot of genes and pathways, however, its precise molecular mechanisms remain poorly understood. In the present study, the breast muscle tissue of female Wenchang chickens (WC) (higher IMF content, 1.24 in D120 and 1.62 in D180) and female White Recessive Rock chickens (WRR; lower IMF content, 0.53 in D120 and 0.90 in D180) were subjected to RNA-sequencing (RNA-seq) analysis. Results showed that many genes related to lipid catabolism, such as SLC27A1, LPL, ABCA1, and CPT1A were down-regulated in WC chickens, and these genes were involved in the PPAR signaling pathway and formed an IPA® network related to lipid metabolism. Furthermore, SLC27A1 was more down-regulated in WRR.D180.B than in WRR.D120.B. Decreased cellular triglyceride (TG) and up-regulated CPT1A were observed in the SLC27A1 overexpression QM-7 cells, and increased cellular triglyceride (TG) and down-regulated CPT1A were observed in the SLC27A1 knockdown QM-7 cells. These results suggest that lower lipid catabolism exists in WC chickens but not in WRR chickens, and lower expression of SLC27A1 facilitate IMF deposition in chicken via down-regulated fatty acid oxidation mediated by CPT1A. These findings indicate that reduced lipid catabolism, rather than increased lipid anabolism, contributes to chicken IMF deposition.

SUBMITTER: Qiu F

PROVIDER: S-EPMC5489693 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Lower Expression of <i>SLC27A1</i> Enhances Intramuscular Fat Deposition in Chicken via Down-Regulated Fatty Acid Oxidation Mediated by <i>CPT1A</i>.

Qiu Fengfang F Xie Liang L Ma Jing-E JE Luo Wen W Zhang Li L Chao Zhe Z Chen Shaohao S Nie Qinghua Q Lin Zhemin Z Zhang Xiquan X

Frontiers in physiology 20170629

Intramuscular fat (IMF) is recognized as the predominant factor affecting meat quality due to its positive correlation with tenderness, juiciness, and flavor. Chicken IMF deposition depends on the balance among lipid synthesis, transport, uptake, and subsequent metabolism, involving a lot of genes and pathways, however, its precise molecular mechanisms remain poorly understood. In the present study, the breast muscle tissue of female Wenchang chickens (WC) (higher IMF content, 1.24 in D120 and 1 ...[more]

PMID: 28706492

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Project description:Skeletal muscle development and intramuscular fat (IMF) content, which positively contribute to meat production and quality, are regulated by precisely orchestrated processes. However, changes in three-dimensional chromatin structure and interaction, a newly emerged mediator of gene expression, during the skeletal muscle development and IMF deposition have remained unclear. In the present study, we analyzed the differences in muscle development and IMF content between one-day-old commercial Arbor Acres broiler (AA) and Chinese indigenous Lushi blue-shelled-egg chicken (LS) and performed Hi-C analysis on their breast muscles. Our results indicated that significantly higher IMF content, however remarkably lower muscle fiber diameter was detected in breast muscle of LS chicken compared to that of AA broiler. The chromatin intra-interaction was prior to inter-interaction in both AA and LS chicken, and chromatin inter-interaction was heavily focused on the small and gene-rich chromosomes. For genomic compartmentalization, no significant difference in the number of B type compartments was found, but AA had more A type compartments versus LS. The A/B compartment switching of AA versus LS showed more A to B switching than B to A switching. There were no significant differences in the average sizes and distributions of topologically associating domains (TAD). Additionally, approximately 50% of TAD boundaries were overlapping. The reforming and disappearing events of TAD boundaries were identified between AA and LS chicken breast muscles. Among these, the HMGCR gene was located in the TAD-boundary regions in AA broilers, but in TAD-interior regions in LS chickens, and the IGF2BP3 gene was located in the AA-unique TAD boundaries. Both HMGCR and IGF2BP3 genes exhibited increased mRNA expression in one-day-old AA broiler breast muscles. It was demonstrated that the IGF2BP3 and HMGCR genes regulated by TAD boundary sliding were potential biomarkers for chicken breast muscle development and IMF deposition. Our data not only provide a valuable understanding of higher-order chromatin dynamics during muscle development and lipid accumulation but also reveal new insights into the regulatory mechanisms of muscle development and IMF deposition in chicken.

Project description:Nasopharyngeal carcinoma (NPC) has a particularly high prevalence in southern China, southeastern Asia and northern Africa. Radiation resistance remains a serious obstacle to successful treatment in NPC. This study aimed to explore the metabolic feature of radiation-resistant NPC cells and identify new molecular-targeted agents to improve the therapeutic effects of radiotherapy in NPC. Methods: Radiation-responsive and radiation-resistant NPC cells were used as the model system in vitro and in vivo. Metabolomics approach was used to illustrate the global metabolic changes. 13C isotopomer tracing experiment and Seahorse XF analysis were undertaken to determine the activity of fatty acid oxidation (FAO). qRT-PCR was performed to evaluate the expression of essential FAO genes including CPT1A. NPC tumor tissue microarray was used to investigate the prognostic role of CPT1A. Either RNA interference or pharmacological blockade by Etomoxir were used to inhibit CPT1A. Radiation resistance was evaluated by colony formation assay. Mitochondrial membrane potential, apoptosis and neutral lipid content were measured by flow cytometry analysis using JC-1, Annexin V and LipidTOX Red probe respectively. Molecular markers of mitochondrial apoptosis were detected by western blot. Xenografts were treated with Etomoxir, radiation, or a combination of Etomoxir and radiation. Mitochondrial apoptosis and lipid droplets content of tumor tissues were detected by cleaved caspase 9 and Oil Red O staining respectively. Liquid chromatography coupled with tandem mass spectrometry approach was used to identify CPT1A-binding proteins. The interaction of CPT1A and Rab14 were detected by immunoprecipitation, immunofluorescence and in situ proximity ligation analysis. Fragment docking and direct coupling combined computational protein-protein interaction prediction method were used to predict the binding interface. Fatty acid trafficking was measured by pulse-chase assay using BODIPY C16 and MitoTracker Red probe. Results: FAO was active in radiation-resistant NPC cells, and the rate-limiting enzyme of FAO, carnitine palmitoyl transferase 1 A (CPT1A), was consistently up-regulated in these cells. The protein level of CPT1A was significantly associated with poor overall survival of NPC patients following radiotherapy. Inhibition of CPT1A re-sensitized NPC cells to radiation therapy by activating mitochondrial apoptosis both in vitro and in vivo. In addition, we identified Rab14 as a novel CPT1A binding protein. The CPT1A-Rab14 interaction facilitated fatty acid trafficking from lipid droplets to mitochondria, which decreased radiation-induced lipid accumulation and maximized ATP production. Knockdown of Rab14 attenuated CPT1A-mediated fatty acid trafficking and radiation resistance. Conclusion: An active FAO is a vital signature of NPC radiation resistance. Targeting CPT1A could be a beneficial regimen to improve the therapeutic effects of radiotherapy in NPC patients. Importantly, the CPT1A-Rab14 interaction plays roles in CPT1A-mediated radiation resistance by facilitating fatty acid trafficking. This interaction could be an attractive interface for the discovery of novel CPT1A inhibitors.

Dataset Information

Lower Expression of SLC27A1 Enhances Intramuscular Fat Deposition in Chicken via Down-Regulated Fatty Acid Oxidation Mediated by CPT1A.

Publications

Lower Expression of <i>SLC27A1</i> Enhances Intramuscular Fat Deposition in Chicken via Down-Regulated Fatty Acid Oxidation Mediated by <i>CPT1A</i>.

Similar Datasets

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