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KMID : 0388120120210010029
Journal of Korean Society for the Study of Obesity
2012 Volume.21 No. 1 p.29 ~ p.36
The Effect of AMPK Activation on Wnt and sFRP5 in TNF-¥á Induced Adipocyte Metabolic Dysfunction in 3T3-L1 Cell
Hong Seok-Woo

Lee Jin-Mi
Choi Ji-Hun
Park Se-Eun
Rhee Eun-Jung
Park Cheol-Young
Oh Ki-won
Park Sung-woo
Kim Sun-Woo
Lee Won-young
Abstract
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-¥á-induced inflammation and recovery in 3T3-L1 adipocyte.

Methods: We stimulated the fully differentiated 3T3-L1 adipocyte with either TNF-¥á only or with both TNF-¥á 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-¥á treatment in fully
differentiated 3T3-L1 adipocyte, and the marked activation of Wnt5a, a noncanonical Wnt ligand, was observed. The
expression of PPAR-¥ã was reduced, and the lipolysis measured by glycerol release, was markedly increased. The
activation of AMPK by AICAR inhibited the TNF-¥á-induced inflammation, reversed the alteration in Wnt signaling
pathway, and reversed fat metabolism induced by TNF-¥á. 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 TNF-¥á 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.
KEYWORD
Adipocyte, Inflammation, Noncanonical Wnt signaling pathway, sFRP5, AMPK, TNF-¥á
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