Korean J Obes.  2012 Mar;21(1):29-36.

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

• Hong SW
• Lee JM
• Choi JH
• Park SE
• Rhee EJ
• Park CY
• Oh KW
• Park SW
• Kim SW
• Lee WY

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-alpha-induced inflammation and recovery in 3T3-L1 adipocyte.
METHODS
We stimulated the fully differentiated 3T3-L1 adipocyte with either TNF-alpha only or with both TNF-alpha 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-alpha treatment in fully differentiated 3T3-L1 adipocyte, and the marked activation of Wnt5a, a noncanonical Wnt ligand, was observed. The expression of PPAR-gamma was reduced, and the lipolysis measured by glycerol release, was markedly increased. The activation of AMPK by AICAR inhibited the TNF-alpha-induced inflammation, reversed the alteration in Wnt signaling pathway, and reversed fat metabolism induced by TNF-alpha. 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-alpha 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-alpha

MeSH Terms

3T3-L1 Cells
Adipocytes
Adipose Tissue
Aminoimidazole Carboxamide
Blotting, Western
Cytokines
Glycerol
Inflammation
Interleukin-6
Lipolysis
Metabolic Diseases
Obesity
Ribonucleotides
Tumor Necrosis Factor-alpha
Wnt Signaling Pathway
Aminoimidazole Carboxamide
Cytokines
Glycerol
Interleukin-6
Ribonucleotides
Tumor Necrosis Factor-alpha