Suppressing NLRP2 expression accelerates hepatic steatosis: A mechanism involving inflammation and oxidative stress
- Department of Gastroenterology, Xuzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Xuzhou, 221000 (China)
- Department of Oncology, Xuzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Xuzhou, 221000 (China)
- Department of Traditional Chinese Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210009 (China)
Highlights: • NLRP2 knockout enhances HFD-elicited metabolic syndrome and insulin resistance. • NLRP2 deletion accelerates inflammation and oxidative stress in liver of HFD-fed mice. • NLRP2 regulates Nrf2 to meditate inflammation and oxidative stress in primary hepatocytes treated with palmitate. Nonalcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation and inflammation in the liver, contributing to a broad spectrum of severe pathologies, such as metabolic syndrome and hepatocellular carcinoma. Presently, the pathogenesis that attributes to NAFLD has not been fully understood. NLRP2 has been shown to inhibit the NF-κB signaling, and thus may contribute to regulate the inflammatory response. However, its role in NAFLD is largely unclear. In the study, we found that NLRP2 was markedly decreased in liver tissues of individuals with severe steatosis, or in a genetic deficiency (ob/ob) mice. High fat diet (HFD) feeding also led to a significant reduction of NLRP2 in liver of mice. Then, the wild type (WT) and NLRP2 knockout (KO) mice were used to further explore the role of NLRP2 in the NAFLD progression. NLRP2 knockout mice exhibited severer metabolic syndrome and hepatic steatosis after HFD administration, as evidenced by the increased body weight, liver histological changes and lipid accumulation. Moreover, HFD feeding-induced inflammation was significantly accelerated by the loss of NLRP2, as evidenced by the increased expression of pro-inflammatory cytokines and activation of nuclear factor κB (NF-κB) pathway. In addition, oxidative stress triggered by HFD was further promoted by NLRP2 deletion through repressing NF-E2-related factor 2 (Nrf2) pathway. In vitro, we surprisingly found that promoting Nrf2 activation could attenuate NLRP2 knockout-accelerated inflammation and reactive oxygen species (ROS) generation. Therefore, our study indicated that NLRP2 might be a potential target for developing effective therapeutic strategy to prevent NAFLD progression.
- OSTI ID:
- 23107875
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 507, Issue 1-4; Other Information: Copyright (c) 2018 Published by Elsevier Inc.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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