Oxytocin receptor enhances adipocyte browning and energy metabolism in mice

Obesity is characterized by abnormal adipose tissue development and disrupted energy metabolism, involving multiple factors. Oxytocin receptor (OXTR) influences social behaviors, mammary gland development and reproduction. In this study, a transgenic mouse model with universal OXTR overexpression under the β-actin promoter (⁺⁺Oxtr) was employed. Both ⁺⁺Oxtr males and females exhibited a lean phenotype with reduced fat accumulation, despite unchanged food consumption. OXTR overexpression enhanced energy expenditure, adaptive thermogenesis and glucose tolerance. Morphologically, OXTR overexpression induced adipose tissue browning, marked by increased cell density and smaller adipocytes. Gene expression analysis revealed elevated levels of Brown Adipose Tissue (BAT) markers, fatty acid transport proteins and glucose transporters in adipose tissues. High OXTR ameliorated high-fat diet (HFD)-induced obesity with improvement of metabolic parameters. Mechanistically, OXTR overexpression led to an activation of PPAR signaling, increased energy expenditure, reduced fat deposition and promoted weight loss. These findings identify OXTR as a critical regulator of energy metabolism and thermogenesis. The ability of OXTR to enhance adaptive thermogenesis and energy metabolism suggests it may serve as a novel therapeutic target for metabolic disorders.