Lysosomal signaling in adipogenesis regulation: A novel pathway to enhance marbled beef quality

Marbled beef, characterized by intramuscular fat (IMF) interspersed within muscle fibers, is a key determinant of meat quality. This study explores the molecular mechanisms underlying the interactions between bovine adipocytes (BAds) and bovine skeletal muscle cells (BSMCs) using a Transwell co-culture system. BAds and BSMCs were isolated and validated for purity and differentiation potential. Co-culture experiments revealed that BAds co-cultured with BSMCs exhibited significantly reduced proliferation and differentiation compared to BAds cultured alone, accompanied by the downregulation of key adipogenesis-related genes and proteins. Transcriptomic analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment identified the lysosome signaling pathway as a critical regulatory mechanism in this interaction. Activation of the lysosome signaling pathway with endoperoxide-6 (EN6) suppressed adipogenesis by reducing the phosphorylation levels of key signaling proteins. Conversely, lysosomal inhibition with chloroquine (CQ) enhanced lipid deposition by increasing the phosphorylation levels of these proteins. Furthermore, zinc finger protein 423 (ZNF423) was identified as a potential downstream effector of lysosomal signaling, suggesting its pivotal role in regulating adipogenesis. These findings provide new insights into the molecular mechanisms governing IMF deposition and highlight lysosomal signaling as a potential target for strategies aimed at improving meat quality.