Resistin is a cysteine-rich signaling hormone associated with immune communication, inflammatory regulation, vascular signaling, and metabolic adaptation. In humans, resistin is produced primarily by immune cells rather than adipocytes, making its biology different from many early rodent-based observations. Its primary physiological role is participation in communication between inflammatory pathways and metabolic tissues. Resistin influences cytokine production, endothelial activation, glucose metabolism, oxidative signaling, and leukocyte recruitment. Through these actions it contributes to coordination between innate immune activity and systemic metabolic responses.
Resistin signaling affects expression of inflammatory mediators including interleukin pathways, adhesion molecules, chemokine signaling systems, and nuclear transcription pathways involved in immune activation. The hormone can influence endothelial permeability, vascular tone regulation, and cellular responses to inflammatory stress. Resistin also interacts with adipose tissue signaling networks and may alter communication between macrophages and adipocytes in metabolically active tissues.
Human resistin is produced mainly by monocytes, macrophages, bone marrow cells, splenic immune cells, pulmonary immune populations, and adipose-associated inflammatory cells. The RETN gene encodes resistin, which is synthesized as a precursor protein and secreted into circulation after intracellular processing. The mature protein can form multimeric structures that influence receptor interactions and downstream signaling activity.
Unlike rodent physiology, where adipocytes are major sources of circulating resistin, human production is dominated by immune-cell pathways. This distinction is important because it places resistin more directly within inflammatory endocrine biology rather than purely adipose endocrine regulation. Resistin secretion increases when macrophages become activated in inflammatory tissue environments. Immune infiltration into adipose tissue, liver tissue, vascular tissue, and connective tissue may contribute to elevated circulating levels.
Resistin production is regulated by inflammatory cytokines, immune receptor activation, oxidative stress, nutrient excess, and innate immune signaling pathways. Signals associated with bacterial pattern recognition, lipopolysaccharide exposure, interleukin activity, and tumor necrosis factor pathways can increase resistin expression in macrophages and monocytes. NF-kB signaling is strongly involved in transcriptional regulation of resistin during inflammatory activation.
Metabolic stress, adipose tissue inflammation, mitochondrial stress, endothelial dysfunction, and reactive oxygen species may also alter circulating resistin levels. Hormonal interactions involving glucocorticoids, insulin signaling, and adipokine communication can further influence expression patterns. Resistin therefore acts as an interface between immune activation and metabolic adaptation, helping coordinate inflammatory responses with vascular, endocrine, and cellular energy-regulating systems.
Resistin participates in metabolic signaling networks that coordinate glucose handling, lipid usage, and immune-linked regulatory adaptation.
