| First Author | Zhu LY | Year | 2021 |
| Journal | Lab Invest | Volume | 101 |
| Issue | 5 | Pages | 588-599 |
| PubMed ID | 33526807 | Mgi Jnum | J:313165 |
| Mgi Id | MGI:6791450 | Doi | 10.1038/s41374-021-00535-3 |
| Citation | Zhu LY, et al. (2021) NLRP3 deficiency did not attenuate NASH development under high fat calorie diet plus high fructose and glucose in drinking water. Lab Invest 101(5):588-599 |
| abstractText | NOD-like receptor protein 3 (NLRP3) promotes the inflammatory response during progression of nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). This study aimed to further delineate the role of NLRP3 in NASH development by abolishing its expression in mice. A high-fat and calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) was used to establish NASH in both wild-type (WT) and NLRP3 knock-out (KO) mice. Hepatocellular injury, hepatic steatosis and fibrosis, as well as inflammatory response and insulin resistance in the liver and epidydimal white adipose tissue (eWAT) were determined. Elevated body weight, liver weight and serum alanine transaminase level, increased hepatic triglyceride accumulation and collagen deposition, and worsened systemic insulin resistance were observed in Nlrp3(-/-) mice compared to WT mice under HFCD-HF/G feeding. Upregulated hepatic transcription of tumor necrosis factor-alpha (TNF-alpha) and monocyte chemotactic protein-1 (MCP-1), and enhanced infiltration of inducible nitric oxide synthase-positive (iNOS(+)) M1 macrophages were also documented in HFCD-HF/G-fed Nlrp3(-/-) mice in comparison to HFCD-HF/G-fed WT mice. Moreover, transcription of TNF-alpha and MCP-1 and infiltration of iNOS(+) M1 macrophages were increased in the liver of Nlrp3(-/-) mice under control diet. NLRP3 deficiency did not attenuate, but instead aggravated NASH development under HFCD-HF/G feeding. The worsened extent of NASH might be attributed to enhanced hepatic MCP-1 expression and M1 macrophage infiltration in Nlrp3(-/-) mice. Our study points to additional caution when NLRP3 blockade is considered as a therapeutic strategy in the treatment of human NASH. |
