APOE mediates the coupling of myogenesis and lipid metabolism in skeletal muscle: Decoding intercellular crosstalk via a cell co-culture model

The growth and lipid accumulation of skeletal muscle directly affects the yield and meat quality characteristics of beef, which is the result of the interaction between skeletal muscle cells (SMCs) and intramuscular adipocytes (IMAs). Therefore, in this study, a co-culture system was used to simulate the in vivo cellular microenvironment, aiming to reveal the interaction patterns between bovine SMCs and IMAs during the proliferation and differentiation stages. The results showed that, compared with SMCs cultured alone, the presence of IMAs in the co-culture system inhibited the expression of proliferation markers such as PCNA, CDK1, CDK2, CCNA2, and CCNE2 in SMCs. This also affected the G1/S phase transition of SMCs, thereby inhibiting their proliferation rate. Meanwhile, the presence of IMAs also inhibited the expression of myogenesis markers such as MYHC, MYOD, MYOG, MYF5, and MYF6, thus hindering the myotube formation process of SMCs. Moreover, RNA-seq identified that the key genes APOE, APOD, SOX9, CAV3, SMPD3 and EDN2 that mediate the interaction between SMCs and IMAs in the co-culture system. Among that, APOE has a dual effect on myogenesis and lipid accumulation. Interfering with the expression of APOE inhibited the proliferation, differentiation and lipid accumulation of SMCs. Based on these findings, we determined that APOE is a key regulatory factor connecting muscle development and fat accumulation. As a potential intervention target, APOE has great potential and can open up new avenues for improving meat quality and production efficiency.