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

Objective: To explore the effect of cordycepin on reducing lipid droplets in adipocytes.

Methods: Rats were fed a 60% high-fat diet to construct a hyperlipidaemia animal model and then treated with cordycepin at different concentrations for 8 weeks. Adipocytes were extracted, and BODIPY staining was used to detect the size of the lipid droplets. The adipocyte membrane proteins ASC-1, PAT2 and P2RX5 were assessed to determine the transformation of white adipocytes to beige and brown adipocytes. In an in vitro study, 3T3-L1 cells were cultured, and Western blotting was used to determine the expression of the lipid droplet-related genes Fsp27, perilipin 3, perilipin 2, PPAR-γ, Rab5, Rab7, Rab11, perilipin 1, ATGL and CGI-58.

Results: We found that cordycepin could promote the transformation of white adipocytes into beige and brown adipocytes. Cordycepin also downregulated the lipid droplet-associated genes Fsp27, perilipin 3, perilipin 2, Rab5, Rab11 and perilipin 1. Moreover, cordycepin reduced the expression of protein CGI-58, which inhibits lipid droplet degradation. In addition, cordycepin significantly increased the expression of ATGL, suggesting that cordycepin might stimulate lipolysis by upregulating the expression of ATGL instead of CGI-58 and by downregulating the expression of perilipin 1.

Conclusions: Cordycepin could blockade lipid droplet formation and promote lipid droplet degradation.