PMID- 34026223
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220423
IS  - 2052-0034 (Print)
IS  - 2052-0034 (Electronic)
VI  - 9
IP  - 2
DP  - 2021 Apr
TI  - Sodium butyrate protects against lipopolysaccharide-induced liver injury 
      partially via the GPR43/ beta-arrestin-2/NF-kappaB network.
PG  - 154-165
LID - 10.1093/gastro/goaa085 [doi]
AB  - BACKGROUND: Butyrate acts as a regulator in multiple inflammatory organ injuries. 
      However, the role of butyrate in acute liver injury has not yet been fully 
      explored. In the present study, we aimed to investigate the association between 
      butyrate and lipopolysaccharide (LPS)-induced acute liver injury and the 
      signaling pathways involved. METHODS: LPS-induced acute liver injury was induced 
      by intraperitoneal injection of LPS (5 mg/kg) in G-protein-coupled receptor 43 
      (GPR43)-knockout (KO) and wild-type female C57BL/6 mice. Sodium butyrate 
      (500mg/kg) was administered intraperitoneally 30 min prior to LPS exposure. Liver 
      injury was detected by serum markers, tissue morphology, and terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). 
      Pro-inflammatory-factor levels were detected by enzyme-linked immunosorbent assay 
      and real-time polymerase chain reaction (RT-PCR). Cell models were first treated 
      with sodium butyrate (4 mumol/mL), followed by LPS (1 mug/mL) half an hour later in 
      GPR43 small interfering RNA (siRNA)-transfected or control RAW264.7 cells. 
      Cell-inflammation status was evaluated through detecting pro-inflammatory-factor 
      expression by RT-PCR and also through checking toll-like receptor 4/nuclear 
      factor-kappaB (TLR4/NF-kappaB)-element levels including TLR4, TRAF6, IKKbeta, Ismall ka, CyrillicBalpha, 
      phospho-Ismall ka, CyrillicBalpha, p65, and phospho-p65 by Western blot. The interaction between GPR43 
      and beta-arrestin-2 was tested by co-immunoprecipitation. RESULTS: Sodium butyrate 
      reversed the LPS-induced tissue-morphology changes and high levels of serum 
      alanine aminotransferase, aspartate transaminase, myeloperoxidase, TUNEL, and 
      pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6. The 
      ameliorating effect of sodium butyrate was weakened in GPR43-KO mice and GPR43 
      siRNA RAW264.7 cells, compared with those of GPR43-positive controls. Sodium 
      butyrate downregulated some elements of the TLR4/NF-kappaB pathway, including 
      phospho-IkappaBalpha and phospho-p65, in RAW264.7 cells. Increased interactions between 
      GPR43 and beta-arrestin-2, and between beta-arrestin-2 and Ismall ka, CyrillicBalpha were observed. 
      CONCLUSION: Sodium butyrate significantly attenuated LPS-induced liver injury by 
      reducing the inflammatory response partially via the GPR43/beta-arrestin-2/NF-kappaB 
      signaling pathway.
CI  - (c) The Author(s) 2020. Published by Oxford University Press and Sixth Affiliated 
      Hospital of Sun Yat-sen University.
FAU - Luo, Qian-Jiang
AU  - Luo QJ
AUID- ORCID: 0000-0002-1660-3864
AD  - Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangzhou, Guangdong, P. R. China.
AD  - Department of Gastroenterology, The Eighth Affiliated Hospital of Sun Yat-sen 
      University (Shenzhen Futian Hospital), Shenzhen, Guangdong, P. R. China.
FAU - Sun, Mei-Xing
AU  - Sun MX
AD  - Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangzhou, Guangdong, P. R. China.
FAU - Guo, Yun-Wei
AU  - Guo YW
AD  - Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangzhou, Guangdong, P. R. China.
FAU - Tan, Si-Wei
AU  - Tan SW
AD  - Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangzhou, Guangdong, P. R. China.
FAU - Wu, Xiao-Ying
AU  - Wu XY
AD  - Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangzhou, Guangdong, P. R. China.
FAU - Abassa, Kodjo-Kunale
AU  - Abassa KK
AD  - Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangzhou, Guangdong, P. R. China.
FAU - Lin, Li
AU  - Lin L
AD  - Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangzhou, Guangdong, P. R. China.
FAU - Liu, Hui-Ling
AU  - Liu HL
AD  - Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangzhou, Guangdong, P. R. China.
FAU - Jiang, Jie
AU  - Jiang J
AD  - Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangzhou, Guangdong, P. R. China.
FAU - Wei, Xiu-Qing
AU  - Wei XQ
AD  - Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangzhou, Guangdong, P. R. China.
LA  - eng
PT  - Journal Article
DEP - 20201122
PL  - England
TA  - Gastroenterol Rep (Oxf)
JT  - Gastroenterology report
JID - 101620508
PMC - PMC8128024
OTO - NOTNLM
OT  - G-protein-coupled receptor 43
OT  - NF-kappaB
OT  - lipopolysaccharide-induced liver injury
OT  - short-chain fatty acids
OT  - sodium butyrate
OT  - beta-arrestin-2
EDAT- 2021/05/25 06:00
MHDA- 2021/05/25 06:01
PMCR- 2020/11/22
CRDT- 2021/05/24 08:09
PHST- 2020/04/30 00:00 [received]
PHST- 2020/10/11 00:00 [revised]
PHST- 2020/10/15 00:00 [accepted]
PHST- 2021/05/24 08:09 [entrez]
PHST- 2021/05/25 06:00 [pubmed]
PHST- 2021/05/25 06:01 [medline]
PHST- 2020/11/22 00:00 [pmc-release]
AID - goaa085 [pii]
AID - 10.1093/gastro/goaa085 [doi]
PST - epublish
SO  - Gastroenterol Rep (Oxf). 2020 Nov 22;9(2):154-165. doi: 10.1093/gastro/goaa085. 
      eCollection 2021 Apr.