The role of abhydrolase domain-containing 15 (Abhd15) in lipid metabolism in adipocytes

Background and Aims: Deregulated lipid metabolism is closely related to many metabolic diseases. Abhd15 expression is strongly increased during adipocyte differentiation and regulated by nutritional changes. Abhd15 associates with phosphodiesterase 3B (PDE3B) and they have the same tissue and subcellular distribution. In white adipose tissue (WAT), PDE3B controls intracellular cyclic AMP level and is thus required for the inhibition of lipolysis by insulin. We hypothesize that Abhd15 affects lipolysis through interaction with PDE3B.

Results: To study the impact of Abhd15 on lipolysis in vitro, we generated 3T3-L1 cells stably overexpressing Abhd15 (Abhd15 o/e) and differentiated them into adipocytes. Our results show that Abhd15 o/e strongly increased basal glycerol release and phosphorylation of HSL at Ser660 in adipocytes. In Cos7 cells, we confirmed the interaction of Abhd15 with PDE3B and we could further show it in adipocytes. Additionally, increasing protein expression of Abhd15 reduced PDE3B protein expression in Cos7 cells and adipocytes. Concomitantly, PDE3B activity was inhibited by membrane fraction lysates from Abhd15 o/e Cos7 cells. We also investigated Abhd15 protein expression at different nutritional states in WAT. While fasting decreased Abhd15 expression, refeeding strongly increased it. PDE3B has the same expression pattern as Abhd15. Also, in WAT of Abhd15-ko mice, PDE3B mRNA and protein expression are strongly reduced in fasted and refed. Accordingly, our in vivo results show that Abhd15-ko mice do not shut down lipolysis after insulin injection.

Conclusion: Our data show that Abhd15 impacts PDE3B expression and activity, thereby affecting lipolysis in vitro and in vivo. In summary, we present Abhd15 as a novel regulator of PDE3B and suggest that Abhd15 plays an important role in insulin signaling, such as lipolysis and adaption to nutritional changes.