Decoding the adipose-fibrotic axis: multi-organ mechanisms, crosstalk networks and emerging therapeutic targets

Abstract

Adipose tissue is a dynamic endocrine and immunometabolic organ that shapes fibrotic remodeling within and beyond its anatomical boundaries. This review synthesizes evidence across skin, heart, liver and intestine to articulate a unifying adipose-fibrotic axis. We highlight depot- and stage-specific mechanisms, including adipokine signaling, adipocyte-to-myofibroblast transition, disordered lipid metabolism, and microbiome-mesenteric fat interactions, and distill convergent pathways. We further propose a stage-dependent model in which early lipolysis can be protective whereas sustained lipolysis promotes fibrosis, yielding testable therapeutic windows. Finally, we map a transitional landscape spanning cellular (ADSCs/exosomes), metabolic (browning/thermogenesis) and microbiome-directed strategies, and we outline outstanding questions for clinical translation.