The Effect of AMPK Activation on Wnt and sFRP5 in TNF-α Induced Adipocyte Metabolic Dysfunction in 3T3-L1 Cell

Background: Chronic inflammation in adipose tissue is closely associated with metabolic diseases, such as, type 2 diabetes and obesity. In the present study, we investigated the Wnt signaling pathway and fat metabolism in the course of TNF-α-induced inflammation and recovery in 3T3-L1 adipocyte. Methods: We stimulated the fully differentiated 3T3-L1 adipocyte with either TNF-α only or with both TNF-α and AICAR for 24 hrs to induce inflammation. We assessed the alteration of Wnt signaling pathway and the factors associated with fat metabolism with western blot assay and real-time PCR. Results: The expression of inflammatory cytokines, IL-6 and MCP-1, was increased by TNF-α treatment in fully differentiated 3T3-L1 adipocyte, and the marked activation of Wnt5a, a noncanonical Wnt ligand, was observed. The expression of PPAR-γ was reduced, and the lipolysis measured by glycerol release, was markedly increased. The activation of AMPK by AICAR inhibited the TNF-α-induced inflammation, reversed the alteration in Wnt signaling pathway, and reversed fat metabolism induced by TNF-α. AMPK activation stimulated the secretion of sFRP5, an anti-inflammatory and anti-Wnt signaling adipokine. Conclusion: The activation of AMPK suppressed noncanonical Wnt signaling pathway and protected the adipoctye from inflammation and lipolysis, induced by TNFα treatment, by sFRP5 stimulation. Based on these results, we suggest that noncanonical Wnt signaling pathway and sFRP may have important roles in metabolic diseases such as, obesity and diabetes.