The calcium-sensing receptor (CaSR), has been documented for its role in the regulation of adipocyte proliferation and adipose tissue dysfunction, and represents a promising target for anti-inflammatory therapeutic approaches. In the previous study, we found the dietary peptide, gamma-L-glutamyl-L-valine (γ-EV), acts as the agonistic of CaSR to suppress tumor necrosis factor (TNF)-α-induced inflammatory responses in intestinal epithelial cells. Therefore, we investigated the anti-inflammatory effect of γ-EV on mouse adipocytes and explore the role of γ-EV-activated CaSR in the regulation of cellular homeostasis using the mouse 3T3-L1 cell line in vitro model. The pretreatment with γ-EV suppressed the production of pro-inflammatory cytokines, i.e. IL-6; MCP-1, while enhancing the expression of PPARγ and adiponectin. Elevated expression of Wnt5a was detected in γ-EV treated cells, suggesting the involvement of the Wnt/β-catenin pathway. In addition, phosphorylation of β-catenin was shown to be significantly inhibited by TNF-α, but restored when cells were pretreated with γ-EV. Concentrations of serine phosphorylated IRS-1 were shown to be lower in γ-EV treated cells, indicating γ-EV may also prevent inflammation in the context of insulin resistance. These findings suggest γ-EV-induced CaSR activation not only prevents TNF-α-induced inflammation in adipocytes but also modulates the crosstalk between Wnt and PPARγ pathways. The synergistic effect on PPARγ and adiponectin as well as the alteration on Wnt5a expression with γ-EV treatment give the evidence that γ-EV plays a significant role in metabolism of adipocytes by the activation of CaSR induced Wnt noncanonical pathway.

Impact of dietary γ-glutamylvaline (EV) against TNF-alpha induced inflammatory response in adipocytes via the activation of CaSR and PPAR-γ pathways

2019 Fall National Meeting

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