Kinin receptors in adipose tissue: drivers of inflammation and metabolic dysfunction in obesity

Kinins, bioactive peptides produced through the proteolytic activity of kallikrein1, are members of the kallikrein-kinin system (KKS) and play crucial roles in regulating physiological processes such as inflammation, blood pressure, vascular permeability, and cell function and growth. In adipose tissue, bradykinin (BK) and des-Arg9-BK (DBK), produced by plasma kallikrein (KLKB1), act via their receptors B2 (B2R) and B1 (B1R), respectively. B1R predominates in preadipocytes, while B2R is expressed during adipogenesis, likely driving adipose tissue expansion and sustaining chronic low-grade inflammation, both hallmarks of obesity and its associated metabolic disorders. Obesity, a multifactorial metabolic disease, is closely linked to adipose tissue dysfunction. This dysfunction is driven by inflammation and oxidative stress, which in turn alter adipogenesis, lipolysis, and insulin and leptin signaling, contributing to obesity and its comorbidities.

This review focuses on the role of the KKS in adipose tissue homeostasis and function.

Evidence from animal models suggests that B1R ablation or antagonism results in a healthier phenotype, characterized by improved leptin and insulin sensitivity, increased lipid oxidation, reduced adipose hypertrophy, and diminished production of proinflammatory mediators and reactive oxygen species. Conversely, B2R activation may exert protective effects by enhancing insulin signaling and promoting glucose uptake, although its role remains incompletely understood and appears context-dependent.

The KKS proposes it as a promising therapeutic target, biomarker, and prognostic indicator in anti-obesity pharmacological strategies.