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BAT (brown adipose tissue) is an important thermoregulatory effector in small mammals, but also contribute to cold defense in both infant and adult humans.It is well established that the BAT thermogenesis is regulated by MnPO (median preoptic nucleus) and MPO (medial preoptic nucleus), while, the underlying molecular mechanism remains unknown.Here, we show the TRPV4 (transient receptor potential vanilloid 4)which has been reported to be strongly expressed in MnPO and its increased expression and activation of TRPV4in MnPO causes the activation of BAT thermogenesis whereas its deactivation suppresses it.When we used TRPV4specific agonist 4α-PDD (4α-phorbol-12,13-didecanoate) along with cold exposure, core body temperature can be maintained as normal and BAT thermogenesis was activated, while the application of TRPV4 specific antagonist RN 1734 (2,4-Dichloro-N-isopropyl-N-(2-isopropylaminoethyl) benzenesulfonamide) along with cold exposure decreased core body temperature and BAT thermogenesis was suppressed.Our results suggest that TRPV4 expressed in MnPO plays an important role in regulating BAT thermogenesis.