Oxytocin Receptor Enhances Adipocyte Browning and Energy Metabolism in Mice

Obesity is characterized by abnormal adipose development and disruptive energy metabolism, and with many factors involved. Oxytocin receptor (OXTR) affects social behaviors, mammary gland development and cancers. In this study, transgenic overexpression of OXTR under ß-actin promoter (++Oxtr) exhibited a lean phenotype with reduced fat accumulation and without significant change in food consumption. OXTR overexpression enhanced energy expenditure, adaptive thermogenesis and glucose tolerance. Morphologically, OXTR overexpression displayed a browning phenotype in adipose tissue accompanied by higher cell counts 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 induced obesity with improvement of metabolic parameters. Furthermore, OXTR overexpression led to an activation of PPAR signaling, increased energy consumption, reduced fat accumulation and weight loss. We have identified OXTR to be a critical regulator of energy metabolism and thermogenesis. That OXTR enhances adaptive thermogenesis and energy metabolism may present a novel therapeutic target for metabolic disorders. Overall design: To explore the molecular mechanism of OXTR regulating adipose development and energy metabolism, RNAseq was used to analyze differentially expressed genes (DEGs) of ++Oxtr against WT gWAT of mice. 365 DEGs were identified, 286 up and 79 down.