Cordycepin modulate body weight by reducing 1 prolactin via an adenosine A 1 receptor 2 3

14 Cordycepin is an extract from the insect fungus Cordyceps. militaris, which is a traditional 15 medicine with various biological function. In previous studies, cordycepin had been reported with 16 excellent anti-obesity effect, but the mechanism is unclear. A large quantity of evidences showed 17 that prolactin plays an important part in body weight regulation, hyperprolactinemia can promote 18 appetite and accelerate fat deposition. In this study, we explored the molecular mechanism of the 19 anti-obesity effect of cordycepin by reducing prolactin release via an adenosine A1 receptor. In vivo, 20 obese rats model was induced by high fat diet for 5 weeks, the serum and liver lipids coupling with 21 serum prolactin were reduced by treatment of cordycepin, the results suggested that cordycepin is a 22 potential drug for therapying obesity which could be related with prolactin. In vitro, cordycepin 23 could inhibit prolactin secretion in GH3 cells via upregulating the expression of adenosine A1 24 receptor, the inhibition effect could be blocked by an antagonist of adenosine receptor A1 DPDPX, 25 prolactin induced the upregulation of lipogenesis genes PRLR, and P-JAK2 in 3T3-L1 cells. 26 Intriguingly, cordycepin would down-regulate the expression of prolactin receptor (PRLR). Thus, 27 we concluded that cordycepin modulate body weight by reducing prolactin release via an adenosine 28 A1 receptor. 29 Key Works: Cordycepin, Adenosine A1 receptor, prolactin, anti-obesity 30