Key result
GLP-1 reverses NLRP3 upregulation in diabetic rat PVAT, an effect lost with NF-κB activation.
Why the study?
The effect of GLP-1 on NLRP3 inflammasome-induced inflammation in perivascular adipose tissue of diabetic rats and the underlying role of NF-κB signalling required investigation.
Does liraglutide reduce NLRP3 inflammasome-dependent inflammation in perivascular adipose tissue of Zucker diabetic fatty rats?
RCT (n=40)
Randomly divided
Does liraglutide reduce NLRP3 inflammasome-dependent inflammation in perivascular adipose tissue of Zucker diabetic fatty rats?
GLP-1 (liraglutide) alleviates NLRP3 inflammasome-dependent inflammation in perivascular adipose tissue by inhibiting the NF-κB signaling pathway in a diabetic rat model.
Answers are grounded in this paper and cite their sources.
May inform GLP-1 mechanisms in diabetic vascular inflammation; leaves open human translation and clinical relevance.
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)-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. 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. CONCLUSION: GLP-1 may alleviate NLRP3 inflammasome-dependent inflammation in PVAT by inhibiting NF-κB signalling.
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Chen et al. (2021) conducted an RCT in Diabetes-induced inflammation in perivascular adipose tissue (n=40). GLP-1 (liraglutide) vs. 0.9% saline (DM group) and normal controls was evaluated on Protein levels of NLRP3, cleaved caspase-1, IL-1β, IL-18, and GSDMD in PVAT. GLP-1 reversed the marked upregulation of NLRP3, cleaved caspase-1, IL-1β, IL-18, and GSDMD in perivascular adipose tissue of diabetic rats, an effect lost with NF-κB activation.
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