Tetrandrine improves obesity-induced adipose metabolic disorders through suppressing macrophage NF-κB activation.

Obesity is closely associated with chronic low-grade inflammation in adipose tissue, which drives systemic metabolic dysfunction. Tetrandrine (TET), a bisbenzylisoquinoline alkaloid from Stephania tetrandra, exhibits potent anti-inflammatory and immunomodulatory effects, yet its impact on obesity-associated metabolic disorders remains unclear. Administration of TET significantly attenuated body weight gain, adipose tissue mass, glucose intolerance, and hyperinsulinemia in diet-induced and genetic obese mouse models. Histological analyses of adipose tissues revealed that TET treatment decreased adipocyte hypertrophy, macrophage infiltration, and fibrosis, which were corroborated by transcriptomic and protein-level assessments showing downregulation of pro-inflammatory cytokines and inhibition of NF-κB signaling. In vitro, TET suppressed NF-κB activation in macrophages without affecting adipocyte differentiation, indicating macrophages as one of potential cellular targets. Collectively, these findings support TET as a promising immunometabolic regulator capable of restoring adipose tissue homeostasis and improving systemic metabolic health, providing evidence for the therapeutic potential of natural bioactive compounds in obesity-related metabolic disorders.