Molecular mechanisms of fat deposition: IL-6 is a hub gene in fat lipolysis, comparing thin-tailed with fat-tailed sheep breeds.

ABSTRACT

Tail fat content affects meat quality and varies significantly among different breeds of sheep. Ghezel (fat-tailed) and Zel (thin-tailed) are two important Iranian local sheep breeds with different patterns of fat storage. The current study presents the transcriptome characterization of tail fat using RNA sequencing in order to get a better comprehension of the molecular mechanism of lipid storage in the two mentioned sheep breeds. Seven (Zel  =  4 and Ghezel  =  3) 7-month-old male lambs were used for this experiment. The results of sequencing were analyzed with bioinformatics methods, including differentially expressed genes (DEGs) identification, functional enrichment analysis, structural classification of proteins, protein-protein interaction (PPI) and network and module analyses. Some of the DEGs, such as LIPG, SAA1, SOCS3, HIF-1 α , and especially IL-6, had a close association with lipid metabolism. Furthermore, functional enrichment analysis revealed pathways associated with fat deposition, including "fatty acid metabolism", "fatty acid biosynthesis" and "HIF-1 signaling pathway". The structural classification of proteins showed that major down-regulated DEGs in the Zel (thin-tailed) breed were classified under transporter class and that most of them belonged to the solute carrier transporter (SLC) families. In addition, DEGs under the transcription factor class with an important role in lipolysis were up-regulated in the Zel (thin-tailed) breed. Also, network analysis revealed that IL-6 and JUNB were hub genes for up-regulated PPI networks, and HMGCS1, VPS35 and VPS26A were hub genes for down-regulated PPI networks. Among the up-regulated DEGs, the IL-6 gene seems to play an important role in lipolysis of tail fat in thin-tailed sheep breeds via various pathways such as tumor necrosis factor (TNF) signaling and mitogen-activated protein kinase (MAPK) signaling pathways. Due to the probable role of the IL-6 gene in fat lipolysis and also due to the strong interaction of IL-6 with the other up-regulated DEGs, it seems that IL-6 accelerates the degradation of lipids in tail fat cells.