Integrated multi-omics analysis reveals metabolic adaptation of Hu sheep skeletal muscle satellite cells induced by an insulin-containing adipogenic differentiation cocktail: inhibiting proliferation while promoting myogenesis

Abstract Background Skeletal muscle satellite cells (SMSCs) possess bidirectional differentiation potential and are important targets for improving meat quality in animal production. However, SMSCs do not spontaneously undergo adipogenesis, and insulin is a classic adipogenic inducer that also affects myogenesis. In this study, SMSCs were isolated from the longissimus dorsi muscle of 1-day-old Hu sheep, cultured and identified. The cells were then induced to differentiate with an insulin-containing adipogenic differentiation cocktail (DMI: dexamethasone, 3-isobutyl-1-methylxanthine, and insulin). Samples were collected before adipogenic induction (No_AD) and after adipogenic induction (AD) for proteomic, lipidomic, and transcriptomic analysis. Results Proteomic analysis revealed that cells induced by the DMI exhibited a protein expression profile suggesting inhibited proliferation and promoted myogenesis. This was accompanied by changes in membrane-associated lipids (PE, Cer). Integrated multi-omics analysis indicated that the sphingolipid metabolism pathway was significantly enriched in both the proteome and lipidome. Differentially expressed genes common to both the proteome and transcriptome were significantly enriched in muscle structure maintenance and cell cycle regulation. Gene-lipid correlation loading plots and correlation coefficients collectively suggested that membrane fusion and cell proliferation were inhibited. This inhibition may be due to cell cycle arrest at the S phase. Conclusions In conclusion, under DMI induction, Hu sheep SMSCs may exhibit a metabolic adaptive state characterized by “inhibited proliferation and promoted myogenesis”, providing a theoretical basis for understanding the metabolic adaptability of satellite cells and utilizing their bidirectional differentiation potential to improve meat quality.