Background and purpose: Cholecystokinin (CCK) promotes triglyceride storage and adiponectin production in white adipose tissue (WAT), suggesting that CCK modulates WAT homeostasis. Our goal was to investigate the role of CCK in regulating the expression and function of the aquaglycerol channel aquaporin 7 (AQP7), a protein that is pivotal for maintaining adipocyte homeostasis and preserving insulin responsiveness.
Experimental approach: The effect of the bioactive fragment of CCK, CCK-8, in regulating adipose AQP7 expression and glycerol efflux was assessed in rats as well as in preadipocytes. Moreover, the involvement of insulin receptors in the effects of CCK-8 was characterized in preadipocytes lacking insulin receptors.
Key results: CCK-8 induced AQP7 gene expression in rat WAT, concomitantly increasing plasma glycerol concentration. In isolated preadipocytes, CCK-8 also enhanced both AQP7 expression and glycerol leakage. The effects of CCK-8 were independent of the lipolysis rate, as CCK-8 failed to promote fatty acid release by adipocytes. In addition, CCK-8 did not enhance hormone sensitive lipase phosphorylation, which is the rate-limiting step of lipolysis. Moreover, the effects of CCK-8 were dependent on the activation of protein kinase B and PPARγ. Silencing insulin receptor expression inhibited CCK-8-induced Aqp7 expression in preadipocytes. Furthermore, insulin enhanced the effect of CCK-8.
Conclusions and implications: CCK regulates AQP7 expression and function, and this effect is dependent on insulin. Accordingly, CCK receptor agonists could be suitable for preserving and improving insulin responsiveness in WAT.
Keywords: diabetes; glycerol; insulin sensitivity; lipolysis; obesity; white adipose tissue.
© 2022 The British Pharmacological Society.