Conclusion
GLP-1 may alleviate NLRP3 inflammasome-dependent inflammation in PVAT by inhibiting NF-κB signalling.
Methods
Thirty ZDF rats were randomly divided into three study groups: DM (0.9% saline, subcutaneously); DM+GLP-1 (liraglutide, s.c.); and NF-κB+GLP-1 (betulinic acid then liraglutide, s.c.). Ten Zucker lean rats were examined as normal controls. PVAT from ZDF (DM) rats was examined for inflammasome mRNA. Protein levels of NLRP3, cleaved caspase-1, caspase-1, gasdermin D (GSDMD), interleukin (IL)-1β and IL-18 in PVAT were compared between control, DM and DM+GLP-1 groups. Protein levels of NLRP3, IL-1β, IL-18 and NF-κB in PVAT were compared between control, DM, DM+GLP-1 and NF-κB+GLP-1 groups.
Results
The inflammasome most abundantly expressed in ZDF rat PVAT was NLRP3. NLRP3, cleaved caspase-1, IL-1β, IL-18, and GSDMD were markedly upregulated in DM versus control tissue, and GLP-1 reversed this effect. Inhibition of NLRP3 inflammasome-associated inflammation by GLP-1 was lost by activation of NF-κB with betulinic acid.