Context: Zinc-α2-glycoprotein (ZAG) induces lipid mobilization in adipose tissue (AT) and stimulates energy utilization in AT and skeletal muscle by up-regulation of UCP isoforms and GLUT4.
Objective: Our study aimed to investigate whether ZAG activates AMPKα, an important regulator of energy metabolism, in human skeletal muscle cells (SkMc).
Materials and methods: SkMc were treated with recombinant ZAG, and activation of AMPKα and ACC, protein abundance of GLUT4, and UCP2 and UCP3 gene expression were analysed.
Results: Treatment of SkMc with ZAG induced short-time phosphorylation of AMPKα and ACC. Furthermore, AMPKα phosphorylation was elevated after 24 h, while for ACC no activation was observed. GLUT4 level was increased by 1.3-fold. However, UCP2 and UCP3 expression remained unaltered.
Discussion and conclusion: These results show that ZAG leads to phosphorylation of AMPKα and ACC, thereby activating a pathway central to the regulation of energy metabolism. This mechanism may be involved in mediating the effects of ZAG in relation to increased energy utilization.