Knockdown of CTRP6 Reduces Porcine Intramuscular and Subcutaneous Fat Deposition via Different Signaling Pathways

The regulation of porcine subcutaneous (SC) and intramuscular (IM) fat deposition significantly affects pork quality and the lean meat percentage of the carcass, respectively. C1q/tumor necrosis factor-related protein 6 (CTRP6), an adipokine, plays a significant role in regulating animal fat deposition. The purpose of this study is to understand the effects of CTRP6 gene knockdown in IM and SC adipocytes by RNA-seq analysis. A total of 1830 and 2936 differentially expressed genes (DEGs) were identified in SC and IM adipocytes, respectively. 844 were down- and 2092 were upregulated in SC adipocytes, while 648 were down- and 1182 were upregulated in IM adipocytes. Furthermore, 1778 DGEs were detected only in SC adipocytes, 672 DGEs only in IM adipocytes, and 1158 DGEs in both types of adipocytes. GO analysis indicated that DEGs involved in adipocyte differentiation were significantly enriched in both SC and IM adipocytes following treatment with CTRP6-siRNA. In addition, KEGG pathway enrichment analysis revealed differences of metabolic regulation between IM and SC adipocytes. With CTRP6-silencing, the signaling pathways encompassing Ras and arachidonic acid metabolism were significantly enriched in IM adipocytes, while four other signaling pathways encompassing the TNF, MAPK, p53 and adipocytokine pathway were specifically enriched in SC adipocytes. Interestingly, the effect of CTRP6-siRNA treatment was attenuated by ML-097 (a specific Ras activator) in IM adipocytes and SJ-172550 (a specific p53 activator) in SC adipocytes. Based on these findings, we suggest that CTRP6 may be a differential regulator of the development and metabolism of IM and SC adipose tissues.