Adipokines as Regulators of Nitric Oxide Synthase Isoforms Across Organs: Emerging Implications for Gastrointestinal...

Adipose tissue secretes bioactive mediators known as adipokines. Beyond their well-established roles in energy homeostasis, appetite regulation, insulin sensitivity, and inflammation, adipokines have emerged as important modulators of inter-organ communication, influencing cardiovascular, neural, immune, and respiratory functions. Growing evidence indicates that many of these effects involve nitric oxide (NO) signaling. NO is produced by three major nitric oxide synthase (NOS) isoforms: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). Experimental evidence indicates that leptin, adiponectin, and resistin can modulate NOS expression or activity and NO bioavailability in a tissue- and context-dependent manner. In the gastrointestinal tract, these adipokines can influence nitrergic signaling and motility in ex vivo rodent preparations. In this review, we compare leptin-, adiponectin-, and resistin-NOS interactions across multiple organs, evaluating direct findings and their possible involvement in enteric nitrergic neurotransmission and gastrointestinal motor regulation. We highlight an emerging three-way regulatory pattern in which leptin appears to exert context-dependent actions, adiponectin predominantly preserves constitutive nitrergic signaling, and resistin shows acute versus chronic effects that may depend on exposure duration. Although direct enteric evidence remains limited and human studies are needed, a better understanding of adipokine-dependent NOS regulation might provide potential therapeutic approaches for gastrointestinal dysmotility.