Abstract

  Adipose tissue and skeletal muscle are central endocrine organs that communicate through a complex network 
of secreted proteins, including adipokines and myokines, which shape systemic energy balance, insulin 
sensitivity and inflammation. In obesity and type 2 diabetes, this crosstalk becomes dysregulated: pro
inflammatory adipokines (e.g., TNF-α, IL-6, resistin) and reduced levels of protective factors (e.g., adiponectin, 
omentin, irisin, myonectin) drive insulin resistance and ectopic lipid deposition. Targeting these signaling axes 
is therefore an attractive strategy for simultaneously improving obesity and diabetes. Nanomaterials offer 
powerful tools to modulate adipokine and myokine networks, both as delivery systems for drugs and biologics 
that act on adipose and muscle, and as active entities that reprogram tissue microenvironments through immune, 
metabolic and mechanical cues. Engineered nanoparticles, liposomes, polymeric systems and inorganic 
nanostructures can be designed to accumulate in adipose tissue or skeletal muscle, alter local inflammation, 
promote browning and thermogenesis, or stimulate exercise-mimetic signaling, thereby reshaping adipokine
myokine profiles. This review outlines the physiological roles of adipokines and myokines in diabetes–obesity 
crosstalk, summarizes evidence that nanomaterials can modulate these mediators, and discusses mechanistic 
pathways including targeted delivery, immune modulation and organelle-level interventions. It also considers 
safety and translational challenges, including off-target effects, nanotoxicology and variability in human adipose 
and muscle depots. Finally, potential future directions, such as nano–exercise mimetics and combination 
strategies integrating nanomedicine with lifestyle and incretin-based therapies, are highlighted as routes to 
more precise and tissue-specific control of adipose–muscle communication in metabolic disease.