Dataset Information

Fatty acid oxidation restriction triggered by Cpt1b deficiency specific in adult cardiomyocyte (CM) with aMHC-MCM promotes CM dedifferentiation [RNA-seq II]

ABSTRACT: Fatty acid oxidation restriction triggered by Cpt1b deficiency specific in adult cardiomyocyte (CM) with aMHC-MCM promotes CM dedifferentiation [RNA-seq II]

PROVIDER: PRJNA723277 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	SRR14285900.fastq.gz	Fastqsanger.gz
	SRR14285901.fastq.gz	Fastqsanger.gz
	SRR14285902.fastq.gz	Fastqsanger.gz
	SRR14285897.fastq.gz	Fastqsanger.gz
	SRR14285898.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 6

Similar Datasets

Project description:CPT1B, as the major rate-limiting enzyme for fatty acid β-oxidation, involved in the regulation of adipose tissue lipid deposition, but its role in the regulation of goat intramuscular fat (IMF) remains unclear. Here, we conducted knockdown experiments targeting the CPT1B gene in goat intramuscular preadipocytes, resulting in a significant increase in intracellular triglyceride (TAG) content and lipid droplet accumulation. Conversely, the overexpression of CPT1B led to a significant decrease in intracellular TAG content and lipid droplet accumulation. Mechanistically, through RNA-seq analysis of CPT1B knockdown samples, we identified 285 differentially expressed genes (DEGs), including 71 up-regulated and 214 down-regulated genes. Notably, these DEGs were significantly enriched in various KEGG signaling pathways, such as fatty acid metabolism, focal adhesion, FoxO signaling, PI3K-Akt signaling, and MAPK signaling pathways. Gene Set Enrichment Analysis (GSEA) further confirmed the upregulation of the MAPK signaling pathway upon CPT1B knockdown in adipocytes. In rescue experiments, we demonstrated that the addition of a p38MAPK inhibitor (PD169316) to CPT1B-knockdown adipocytes counteracted the increase in lipid deposition caused by the loss of CPT1B function. These findings suggest that CPT1B inhibits lipid deposition in goat intramuscular preadipocytes via the p38MAPK signaling pathway. In addition, we observed a potential interaction between CPT1B and CPT1A through Protein-Protein Interaction Networks (PPIs). Interestingly, CPT1A exhibited a similar regulatory function to CPT1B, and they both were able to partially restore the changes in lipid deposition induced by each other. This observation supports the hypothesis of synergistic effects between CPT1B and CPT1A. Collectively, our results elucidate the role of CPT1B in the regulation of lipid deposition in goat intramuscular adipocytes through the p38MAPK signaling pathway, providing valuable insights for enhancing the quality of goat intramuscular fat.

Project description:Rationale: In virtually all models of heart failure, prognosis is determined by right ventricular (RV) function; thus, understanding the cellular mechanisms contributing to RV dysfunction is critical. Whole organ remodeling is associated with cell-specific changes, including cardiomyocyte dedifferentiation and activation of cardiac fibroblasts (Cfib) which in turn is linked to disorganization of cytoskeletal proteins and loss of sarcomeric structures. However, how these cellular changes contribute to RV function remains unknown. We’ve previously shown significant organ-level RV dysfunction in a large animal model of pulmonary hypertension (PH) which was not mirrored by reduced function of isolated cardiomyocytes. We hypothesized that factors produced by the endogenous Cfib contribute to global RV dysfunction by generating a heterogeneous cellular environment populated by dedifferentiated cells. Objective: To determine the effect of Cfib conditioned media (CM) from the PH calf (PH-CM) on adult rat ventricular myocytes (ARVM) in culture. Methods and Results: Brief exposure (<2 days) to PH-CM results in rapid, marked dedifferentiation of ARVM to a neonatal-like phenotype exhibiting spontaneous contractile behavior. Dedifferentiated cells maintain viability for over 30 days with continued expression of cardiomyocyte proteins including TnI and α-actinin yet exhibit myofibroblast characteristics including expression of α-smooth muscle actin. Using a bioinformatics approach to identify factor(s) that contribute to dedifferentiation, we found activation of the PH Cfib results in a unique transcriptome correlating with factors both in the secretome and with activated pathways in the dedifferentiated myocyte. Further, we identified upregulation of periostin in the Cfib and CM, and demonstrate that periostin is sufficient to drive cardiomyocyte dedifferentiation. Conclusions: These data suggest that paracrine factor(s) released by Cfib from the PH calf signal a phenotypic transformation in a population of cardiomyocytes that likely contributes to RV dysfunction. Therapies targeting this process, such as inhibition of periostin, have the potential to prevent RV dysfunction.

Dataset Information

Fatty acid oxidation restriction triggered by Cpt1b deficiency specific in adult cardiomyocyte (CM) with aMHC-MCM promotes CM dedifferentiation [RNA-seq II]

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets