Abstract

Intramuscular fat (IMF) content is related to insulin resistance, which is an important prediction factor for disorders, such as cardiovascular disease, obesity and type 2 diabetes in human. At the same time, it is an economically important trait, which influences the sensorial and nutritional value of meat. The deposition of IMF is influenced by many factors such as sex, age, nutrition, and genetics. In this study Nellore steers (Bos taurus indicus subspecies) were used to better understand the molecular mechanisms involved in IMF content. This was accomplished by identifying differentially expressed genes (DEG), biological pathways and putative regulatory factors. Animals included in this study had extreme genomic estimated breeding value (GEBV) for IMF. RNA-seq analysis, gene set enrichment analysis (GSEA) and co-expression network methods, such as partial correlation coefficient with information theory (PCIT), regulatory impact factor (RIF) and phenotypic impact factor (PIF) were utilized to better understand intramuscular adipogenesis. A total of 16,101 genes were analyzed in both groups (high (H) and low (L) GEBV) and 77 DEG (FDR 10%) were identified between the two groups. Pathway Studio software identified 13 significantly over-represented pathways, functional classes and small molecule signaling pathways within the DEG list. PCIT analyses identified genes with a difference in the number of gene-gene correlations between H and L group and detected putative regulatory factors involved in IMF content. Candidate genes identified by PCIT include: ANKRD26, HOXC5 and PPAPDC2. RIF and PIF analyses identified several candidate genes: GLI2 and IGF2 (RIF1), MPC1 and UBL5 (RIF2) and a host of small RNAs, including miR-1281 (PIF). These findings contribute to a better understanding of the molecular mechanisms that underlie fat content and energy balance in muscle and provide important information for the production of healthier beef for human consumption.

Highlights

  • Intramuscular fat (IMF, known as marbling) represents the amount of fat accumulated between muscle fibers or within muscle cells, which is the sum of phospholipids, and triglycerides

  • The present study showed the complexity of Longissimus dorsi muscle transcriptome and the molecular mechanisms involved in lipid metabolism related to differences in intramuscular fat (IMF) in extreme IMF genomic estimated breeding values (GEBV) Nellore cattle

  • Differential gene expression and pathway enrichment analysis identified a number of genes and pathways related to adipogenesis and lipid metabolism

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Summary

Introduction

Intramuscular fat (IMF, known as marbling) represents the amount of fat accumulated between muscle fibers or within muscle cells, which is the sum of phospholipids (present in cell membranes), and triglycerides (lipid droplets). Understanding the biological and functional mechanisms that regulate IMF content is an interesting issue in meat science and human medicine. Intramuscular fat content is a polygenic trait regulated by many genes involved directly, or indirectly in adipogenesis and fat metabolism [1]. High intramuscular fat content (marbling) has been associated with tenderness, juiciness and consumer satisfaction [3]. At the same time, red meat consumption or saturated fat consumption has been associated with human diseases, such as cardiovascular disease, obesity and colon cancer [4]. These associations have created a demand for beef with both low fat and high quality by consumers. Consumers in Asia and North America desire beef with high IMF, while Europeans prefer lean beef, with low IMF [5]

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