GLP-1 alleviates NLRP3 inflammasome-dependent inflammation in perivascular adipose tissue by inhibiting the NF-?B signalling pathway.

ABSTRACT:

Objectives

To study the effect of glucagon-like peptide 1 (GLP-1) on NLR family pyrin domain containing 3 (NLRP3) inflammasome-induced inflammation in perivascular adipose tissue (PVAT) of Zucker diabetic fatty (ZDF) rats and the underlying role of nuclear factor (NF)-?B 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-?B+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)-1? and IL-18 in PVAT were compared between control, DM and DM+GLP-1 groups. Protein levels of NLRP3, IL-1?, IL-18 and NF-?B in PVAT were compared between control, DM, DM+GLP-1 and NF-?B+GLP-1 groups.

Results

The inflammasome most abundantly expressed in ZDF rat PVAT was NLRP3. NLRP3, cleaved caspase-1, IL-1?, 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-?B with betulinic acid.

Conclusion

GLP-1 may alleviate NLRP3 inflammasome-dependent inflammation in PVAT by inhibiting NF-?B signalling.

SUBMITTER: Chen X 

PROVIDER: S-EPMC7917887 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature