The role of abhydrolase domain containing 15 (ABHD15) in lipid metabolism

Background/Aims: Abnormal lipid metabolism and lipid signaling are closely related to many human metabolic diseases, such as obesity, type II diabetes and cancer. Abhd15 expression is strongly increased during adipocyte differentiation and regulated by nutritional state, upon high fat diet and obesity. It was reported that Abhd15 binds phosphodiesterase 3B (PDE3B) and thereby we assume that Abhd15 may affect lipolysis through interaction with PDE3B. Methods & Results: We co-transfected PDE3B-Flag and Abhd15-His vectors in Cos7 cells, the co-IP result indicated that PDE3B could interact with Abhd15. And we observed that Abhd15 overexpression didn’t change the fat cell phenotype in 3T3-L1 adipocytes. Then, we differentiated Abhd15 overexpressed 3T3-L1 preadipocytes into mature adipocytes to study lipolysis in vitro. Our results showed that Abhd15 overexpression strongly increased the phosphorylation of HSL at Ser660 and subsequently increased glycerol release in 3T3-L1 adipocytes. Moreover, we found that Abhd15 overexpression reversed insulin-suppressed glycerol release together with PDE inhibitor in 3T3-L1 adipocytes. The transcriptomic studies of Abhd15-ko mice indicated that genes related to fatty acid and phospholipid metabolism processes were strongly reduced in eWAT of Abhd15-ko mice. Consistently, the lipidomic studies of Abhd15-ko mice suggested that many phospholipids were reduced in eWAT of Abhd15-ko mice. Conclusion: Our data suggest that Abhd15 is an inhibitor of its interaction partner PDE3B and thereby raises cAMP level to increase lipolysis. Moreover, the gene and lipid profiles observed in Abhd15-ko mice propose that Abhd15 also play a role in regulating fatty acid and phospholipid metabolism in white adipose tissue.