PMID- 33526807
OWN - NLM
STAT- MEDLINE
DCOM- 20210803
LR  - 20240229
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 101
IP  - 5
DP  - 2021 May
TI  - NLRP3 deficiency did not attenuate NASH development under high fat calorie diet 
      plus high fructose and glucose in drinking water.
PG  - 588-599
LID - S0023-6837(22)00638-9 [pii]
LID - 10.1038/s41374-021-00535-3 [doi]
AB  - 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.
FAU - Zhu, Liu-Yan
AU  - Zhu LY
AD  - Department of Medical Microbiology and Parasitology, MOE/NHC/CAMS Key Laboratory 
      of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University 
      Shanghai Medical College, Shanghai, 200032, China.
FAU - Liu, Chang
AU  - Liu C
AD  - Department of Medical Microbiology and Parasitology, MOE/NHC/CAMS Key Laboratory 
      of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University 
      Shanghai Medical College, Shanghai, 200032, China.
FAU - Li, Zong-Rui
AU  - Li ZR
AD  - Department of Medical Microbiology and Parasitology, MOE/NHC/CAMS Key Laboratory 
      of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University 
      Shanghai Medical College, Shanghai, 200032, China.
FAU - Niu, Chen
AU  - Niu C
AD  - Department of Medical Microbiology and Parasitology, MOE/NHC/CAMS Key Laboratory 
      of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University 
      Shanghai Medical College, Shanghai, 200032, China.
FAU - Wu, Jian
AU  - Wu J
AUID- ORCID: 0000-0002-3394-1507
AD  - Department of Medical Microbiology and Parasitology, MOE/NHC/CAMS Key Laboratory 
      of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University 
      Shanghai Medical College, Shanghai, 200032, China. jian.wu@fudan.edu.cn.
AD  - Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan 
      University, Shanghai, 200032, China. jian.wu@fudan.edu.cn.
AD  - Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, 
      Shanghai, 200032, China. jian.wu@fudan.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210201
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 30237-26-4 (Fructose)
RN  - 9007-34-5 (Collagen)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Collagen/metabolism
MH  - Diet, High-Fat/adverse effects
MH  - Fructose/adverse effects
MH  - Glucose/adverse effects
MH  - Insulin Resistance
MH  - Lipid Metabolism
MH  - Liver/immunology/metabolism
MH  - Male
MH  - Mice, Knockout
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/*metabolism
MH  - Non-alcoholic Fatty Liver Disease/*etiology/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Mice
EDAT- 2021/02/03 06:00
MHDA- 2021/08/04 06:00
CRDT- 2021/02/02 06:05
PHST- 2020/11/02 00:00 [received]
PHST- 2020/12/22 00:00 [accepted]
PHST- 2020/12/21 00:00 [revised]
PHST- 2021/02/03 06:00 [pubmed]
PHST- 2021/08/04 06:00 [medline]
PHST- 2021/02/02 06:05 [entrez]
AID - S0023-6837(22)00638-9 [pii]
AID - 10.1038/s41374-021-00535-3 [doi]
PST - ppublish
SO  - Lab Invest. 2021 May;101(5):588-599. doi: 10.1038/s41374-021-00535-3. Epub 2021 
      Feb 1.