Nucleotide metabolic rewiring enables NLRP3 inflammasome hyperactivation in obesity
The University of Texas Southwestern Medical Center · University of Oxford · +1 more institution
Abstract
Obesity is a major disease risk factor due to obesity-associated hyperinflammation. We found that obesity induced Nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome hyperactivation and excessive interleukin (IL)-1β production in macrophages by disrupting SAM and HD domain-containing protein 1 (SAMHD1), a deoxynucleoside triphosphate (dNTP) hydrolase crucial for nucleotide balance. This caused aberrant accumulation of dNTPs, which can be transported into mitochondria, and initiated mitochondrial DNA (mtDNA) neosynthesis, which increased the presence of oxidized mtDNA and triggered NLRP3 hyperactivation. Deletion of SAMHD1 promoted NLRP3 hyperactivation in cells isolated from zebrafish, mice, and…
Citation impact
- FWCI
- 45.66
- Percentile
- 100%
- References
- 94
Authors
20- DLDanhui Liu
The University of Texas Southwestern Medical Center
- CZChuanli Zhou
The University of Texas Southwestern Medical Center
- XWXiaochen Wang
The University of Texas Southwestern Medical Center
- ZLZhou Luo
The University of Texas Southwestern Medical Center
- RXRuiyao Xu
The University of Texas Southwestern Medical Center
Topics & keywords
- Hyperactivation
- Inflammasome
- Nucleotide
- Pyrin domain
- Mitochondrion
- SAMHD1
- Downregulation and upregulation
- Secretion