Targeting the Adipose–Liver Axis in Fibrosis and Liver Cancer: Pathogenic Mechanisms and Therapeutic Perspectives

Adipose tissue has emerged as a dynamic endocrine and immunometabolism organ that profoundly influences liver homeostasis and disease progression. Accumulating evidence highlights a bidirectional adipose–liver axis through which adipokines, lipid metabolites, inflammatory mediators, and adipocyte‐derived extracellular vesicles orchestrate hepatic stellate cell activation, hepatocyte lipotoxicity, and remodeling of the hepatic immune microenvironment. These inter‐organ signals play essential roles in driving the transition from steatosis to fibrosis and ultimately hepatocellular carcinoma (HCC). Here, we synthesize recent advances delineating how dysregulated adipose metabolism, chronic low‐grade inflammation, and adipose‐derived molecular cues reprogram hepatic cellular states and tumorigenic pathways via mechanisms involving JAK–STAT, NF‐κB, AMPK, and lipid‐regulatory networks, such as SREBP1 and FASN. We further discuss emerging therapeutic strategies targeting adipokine signaling, lipid metabolic rewiring, and adipose–liver communication, as well as the potential of single‐cell and spatial multi‐omics to refine mechanistic understanding. Collectively, these insights underscore the central role of adipose tissue in shaping the fibrotic and oncogenic landscape of the liver and highlight new avenues for metabolic and immunologic intervention.