Cordycepin Modulates Body Weight by Reducing Prolactin Via an Adenosine A1 Receptor

Abstract

Cordycepin is an extract from the insect fungus Cordyceps. militaris with various biological function. In previous studies, cordycepin had been reported with excellent anti-obesity effect, but the mechanism is unclear. Evidences also showed that prolactin played an important role in body weight regulation, hyperprolactinemia can promote appetite and accelerate fat deposition. In this study, we explored the molecular mechanism of the anti-obesity effect of cordycepin. In vivo, obese rats model was induced by high fat diet for 5 weeks, the serum and liver lipids coupled with serum prolactin were reduced by treatment of cordycepin (P＜0.01) , the results suggested that cordycepin is a potential drug for lowering blood and liver lipids and reducing body weight which related with prolactin. Cordycepin also protects adipocytes from enlargement and hepatocytes from lipotoxicity caused inflammation. In vitro, cordycepin could inhibit prolactin secretion in GH3 cells via upregulating the expression of adenosine A1 receptor, the inhibition effect could be blocked by an antagonist of adenosine receptor A1 DPDPX, which demonstrated that cordycepin may work as an adenosine agonist. In addition, cordycepin could inhibit ERK/AKT/PI3K pathway in GH3 cells. Meanwhile, cordycepin could block prolactin induced the upregulation of lipogenesis genes PRLR, and phosphorylation of JAK2 in 3T3-L1 cells. In vivo study, cordycepin would down-regulate the expression of prolactin receptor (PRLR) but not phosphorylation of JAK2. Thus, we concluded that cordycepin modulate body weight by reducing prolactin release via an adenosine A1 receptor.

Cordycepin regulates body weight by inhibiting lipid droplet formation, promoting lipolysis and recruiting beige adipocytes

“…Our earlier laboratory studies have found that cordycepin could prevent body weight gain in mice fed high‐fat diets. In this study, we demonstrated that cordycepin could reduce HFD‐induced obesity by regulating the lipid content of droplets in adipocytes …”

A Systematic Review of the Biological Effects of Cordycepin

“…The effect of cordycepin was also studied in animal models of metabolic diseases, including diabetes and obesity. Cordycepin has been shown to reduce body weight and change fat metabolism in animal models of obesity [ 166 , 238 , 239 , 240 ]. Studies in models of type II diabetes found that cordycepin treatment reduced plasma glucose level, hyperphagia and polydipsia.…”

Metabolic impacts of cordycepin on hepatic proteomic expression in streptozotocin-induced type 1 diabetic mice

“…In contrast, a previous study from Ma et al [17] found that a cordycepin treatment of alloxan-induced diabetic mice remarkably reduced the loss of body weight by normalizing the glucose metabolism. But a previous study reported that cordycepin extracted from C. militaris can reduce gains in body weight of mice [30], and a further study indicated that cordycepin modulates the body weight by reducing prolactin via an adenosine A1 receptor [31]. These studies indicate that a reduction in body weight is associated with a lower food intake in DM-treated mice.…”