Background: Cordycepin is an extract from the insect fungus Cordyceps. militaris with various biological
function. In previous studies, cordycepin has demonstrated an excellent anti-obesity effect, but the mechanism
is unclear. It was also demonstrated that prolactin played an important role in body weight regulation and
hyperprolactinemia can promote appetite and accelerate fat deposition. In this study, we explored the molecular
mechanism of the anti-obesity effect of cordycepin.
Methods: In Vivo, the obese rat model was induced by high fat diet for five weeks, and the serum and liver lipid
levels coupled with the serum prolactin levels were reduced following cordycepin treatment (P<0.01).
Results: The results suggested that cordycepin is a potential drug that lowers blood and liver lipid levels and
reduces body weight related to prolactin. Cordycepin also protects adipocytes from enlargement and hepatocytes
from lipotoxicity-induced inflammation. In vitro, cordycepin inhibited prolactin secretion in GH3 cells via
upregulating the expression of adenosine A1 receptor, and the inhibition effect was blocked by an antagonist of
adenosine receptor A1 DPDPX, demonstrating that cordycepin may work as an adenosine agonist. Additionally,
cordycepin inhibited the ERK/AKT/PI3K pathway in GH3 cells. At the same time, cordycepin blocked prolactininduced
upregulation of lipogenesis genes PRLR, and phosphorylation of JAK2 in 3T3-L1 cells. In an in vivo
study, cordycepin downregulated the expression of prolactin receptor (PRLR) but not the phosphorylation of
Conclusion: Thus, it was proved that cordycepin modulates body weight by reducing prolactin release via an
adenosine A1 receptor.