LKB1 Differently Regulates Adipogenesis in Intramuscular and Subcutaneous Adipocytes through Metabolic and Cytokine-Related Signaling Pathways

Abstract

Liver kinase B1 (LKB1) plays important and various roles in the differentiation and lipid metabolism of adipocytes. However, the current knowledge of the respective roles of LKB1 in subcutaneous fat (SCF) and intramuscular fat (IMF) adipocytes remains unclear. This study aimed to discover the different regulatory mechanisms of LKB1 in SCF and IMF adipocytes. We found that LKB1 overexpression inhibited adipogenesis in both SCF and IMF adipocytes, and SCF adipocytes were more sensitive to regulation by LKB1. Transcriptomics results showed that IMF adipocytes had many more differentially expressed genes (DEGs) than SCF adipocytes. Pathway analysis of the shared and distinct DEGs revealed that the main adipogenesis mechanism was similar between SCF and IMF adipocytes upon LKB1 overexpression, while regulatory and metabolic signaling pathways, such as MAPK, PPAR signaling pathways, were differently regulated by LKB1. Several cytokine-related pathways were only enriched in LKB1-overexpressing IMF adipocytes. Our study reveals different regulators and signaling pathways between SCF and IMF adipocytes under LKB1 overexpression, which may be potential targets to differentially control SCF and IMF deposition and improve our understanding of the regulatory mechanisms of IMF deposition.