Ω3-FA receptor signaling regulates the novel cytokine wnt5a in metabolic inflammation

Introduction:

Obesity is associated with metabolic inflammation in adipose tissue. Wnt5a has been described as a novel cytokine linking metabolic inflammation to insulin resistance. Ω3-FA are supposed to have anti-inflammatory effects. The aim of this study was to examine, the influence of environmental and genetic factors on the wnt5a level and if a stimulation of the Ω3-FA receptor GPR120 might be able to inhibit the wnt5a secretion of primary macrophages.

Methods:

From our FoCus cohort different parameter were measured in serum by ELISA and GPR120 SNPs were sequenced. Human THP1 macrophages were stimulated with fatty acids. siRNA knock-down of TAK1 was used to further dissect the effect of the GPR120 receptor pathway on wnt5a expression and release. Human primary macrophages were stimulated with two different pharmacological GPR120 agonists and wnt5a expression was measured by western blotting.

Results:

Wnt5a correlates positive with IL-6 in non-obese and Triglycerides in obese human subjects. SNPs in the GPR120 receptor gene affect the wnt5a level. In THP1 macrophages stimulation of GPR120 receptor system by anti-inflammatory Ω3-FA decreased wnt5a expression in a TAK1 dependent manner. In primary macrophages wnt5a expression was decreased following the treatment with pharmacological GPR120 agonists.

Conclusion:

Wnt5a is influenced by environmental and genetic factors. The GPR120 receptor is of functional relevance in mediating nutritional effects on wnt5a-mediated macrophage activity. Novel pharmacological agents stimulate the receptors more potent compared to nutritional Ω3-FA. This finding might indicate a novel therapeutic target for an anti-inflammatory therapy on metabolic inflammation in obesity and/or type 2 diabetes.