GPR120 mediates nutritional effects on adipose tissue macrophage activity

Introduction: Obesity is associated with adipose tissue inflammation. Wnt5a has recently been described as a novel cytokine in metabolic inflammation. The aim of the present study was to examine, if stimulation of the Ω-3-fatty acid receptor GPR120 might be able to inhibit wnt5a release from activated adipose tissue macrophages, which might indicate a novel therapeutic target for future diabetes therapy.

Materials and methods: Human THP1 macrophages were stimulated with several fatty acids and with two different pharmacological GPR120 compounds and wnt5a expression was measured by western blotting. siRNA mediated knock-down of GRP120 or β-Arrestin was performed to further specify the effect of the GPR120 receptor system on wnt5a expression and release.

Results: Stimulation of the GPR120 receptor system by Ω-3-fatty acid decreased expression of the pro-inflammatory factor wnt5a in THP1 macrophages. Altered wnt5a expression was also found due to treatment of macrophages with the pharmacological GPR120 agonist “compound A”. Both, GPR120 and β-Arrestin knock-down interfered with wnt5a expression, indicating functional relevance of the receptor system in mediating effects of Ω-3-fatty acid on macrophages.

Conclusion: The GPR120 receptor is of functional relevance in mediating nutritional effects on wnt5a-mediated adipose tissue macrophage activity. Since novel pharmacological agents -e.g. compound A- are able to stimulate the receptors more potent compared to nutritional Ω-3-fatty, this finding might indicate a novel therapeutic target for an anti-inflammatory therapy for obesity and/or type 2 diabetes.