The effects of oxytocin to rectify metabolic dysfunction in obese mice are associated with increased thermogenesis

Oxytocin, a protein hormone mainly produced by hypothalamus, has been shown to repress body weight gain in obese animals, in part, by reducing food intake and increasing energy expenditure. Till now, activation of brown fat tissue (BAT) thermogenesis and white adipose tissue (WAT) browning are considered as two main factors for oxytocin-induced energy expenditure. However, the underlying molecular mechanisms are still not understood well. Here, we observed that oxytocin expression in the hypothalamus and its receptor in adipose tissues were induced by cold exposure in mice. In differentiated adipocytes, oxytocin stimulated brown adipocyte specific gene expression by inducing PRDM16. In high fat diet induced obese mice, oxytocin delivery by osmotic minipumps increased body core temperature and decreased body weight gain. Glucose and insulin tolerance were improved by oxytocin. Hyperinsulinemia and fatty liver were ameliorated in oxytocin-treated animals. Moreover, oxytocin treatment induced thermogenic gene expressions in BAT, inguinal WAT (iWAT), and skeletal muscle. Taken together, our findings revealed a new aspect of oxytocin, i.e. oxytocin induces iWAT browning and stimulates thermogenesis in BAT, iWAT and skeletal muscle, through which oxytocin promotes thermo-genesis and thus combats obesity and metabolic dysfunctions.