PMID- 34273192
OWN - NLM
STAT- MEDLINE
DCOM- 20220315
LR  - 20220315
IS  - 1440-1746 (Electronic)
IS  - 0815-9319 (Linking)
VI  - 36
IP  - 12
DP  - 2021 Dec
TI  - Insulin-like growth factor binding protein 1 ameliorates lipid accumulation and 
      inflammation in nonalcoholic fatty liver disease.
PG  - 3438-3447
LID - 10.1111/jgh.15627 [doi]
AB  - BACKGROUND AND AIMS: Insulin-like growth factor binding protein 1 (IGFBP1) is 
      recently proved to be associated with glucose regulation and insulin resistance. 
      However, little is known about its direct impact on nonalcoholic fatty liver 
      disease (NAFLD). This study aims to investigate the effect and potential 
      mechanism of IGFBP1 in NAFLD. METHODS: We first measured the expression level of 
      IGFBP1 in NAFLD patients, mice, and cells. Then in in vivo study, C57BL/6 mice 
      were fed with a methionine/choline-deficient (MCD) diet for 4 weeks to establish 
      the model of NAFLD. And for the last 2 weeks, the mice were injected 
      intraperitoneally with vehicle or recombinant mouse IGFBP1 0.015 mg/kg/d. The L02 
      cells were treated with free fatty acids (FFA) or palmitate acids (PA) and 
      recombinant IGFBP1 for 48 h. Integrin-linked kinase (ILK) inhibitor and small 
      interfering RNA were used to explore the potential interactions between IGFBP1 
      and integrin beta1 (ITGB1). RESULTS: The expression of IGFBP1 was increased in NAFLD 
      patients, mice, and cells. IGFBP1 treatment significantly ameliorated lipid 
      accumulation and hepatic injury in MCD-fed mice. IGFBP1 downregulated hepatic 
      lipogenesis and upregulated lipid beta-oxidation. In addition, IGFBP1 attenuated the 
      nuclear factor-kappa B (NF-kappaB) and extracellular regulated protein kinases (ERK) 
      signaling pathways. In vitro, we proved that IGFBP1 relieved FFA-induced lipid 
      accumulation via interacting with ITGB1 and alleviated inflammation by inhibiting 
      NF-kappaB and ERK signaling pathways. CONCLUSIONS: IGFBP1 treatment significantly 
      ameliorated hepatic steatosis by interacting with ITGB1 and suppressed 
      inflammation by inhibiting NF-kappaB and ERK signaling pathways. Therefore, IGFBP1 
      might be a potential therapeutic target for NAFLD.
CI  - (c) 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & 
      Sons Australia, Ltd.
FAU - Pan, Jiaqi
AU  - Pan J
AD  - Department of Gastroenterology, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - Cen, Li
AU  - Cen L
AD  - Department of Gastroenterology, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - Zhou, Tianyu
AU  - Zhou T
AD  - Department of Gastroenterology, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - Yu, Mengli
AU  - Yu M
AD  - Department of Gastroenterology, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - Chen, Xueyang
AU  - Chen X
AD  - Department of Gastroenterology, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - Jiang, Wenxi
AU  - Jiang W
AD  - Department of Gastroenterology, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - Li, Youming
AU  - Li Y
AD  - Department of Gastroenterology, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - Yu, Chaohui
AU  - Yu C
AUID- ORCID: 0000-0003-4842-3646
AD  - Department of Gastroenterology, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - Shen, Zhe
AU  - Shen Z
AUID- ORCID: 0000-0003-0604-7558
AD  - Department of Gastroenterology, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, China.
LA  - eng
GR  - 81300303/National Natural Science Foundation of China/
GR  - 81770586/National Natural Science Foundation of China/
GR  - U1803121/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20210730
PL  - Australia
TA  - J Gastroenterol Hepatol
JT  - Journal of gastroenterology and hepatology
JID - 8607909
RN  - 0 (Insulin-Like Growth Factor Binding Protein 1)
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Animals
MH  - Humans
MH  - *Inflammation/prevention & control
MH  - *Insulin-Like Growth Factor Binding Protein 1/pharmacology
MH  - *Lipid Metabolism/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B
MH  - *Non-alcoholic Fatty Liver Disease/drug therapy
OTO - NOTNLM
OT  - insulin-like growth factor binding protein 1
OT  - integrin beta1
OT  - nonalcoholic fatty liver disease
EDAT- 2021/07/18 06:00
MHDA- 2022/03/16 06:00
CRDT- 2021/07/17 17:06
PHST- 2021/06/25 00:00 [revised]
PHST- 2020/11/01 00:00 [received]
PHST- 2021/07/12 00:00 [accepted]
PHST- 2021/07/18 06:00 [pubmed]
PHST- 2022/03/16 06:00 [medline]
PHST- 2021/07/17 17:06 [entrez]
AID - 10.1111/jgh.15627 [doi]
PST - ppublish
SO  - J Gastroenterol Hepatol. 2021 Dec;36(12):3438-3447. doi: 10.1111/jgh.15627. Epub 
      2021 Jul 30.