PMID- 37505920
OWN - NLM
STAT- MEDLINE
DCOM- 20231102
LR  - 20231107
IS  - 1949-0984 (Electronic)
IS  - 1949-0976 (Print)
IS  - 1949-0976 (Linking)
VI  - 15
IP  - 1
DP  - 2023 Jan-Dec
TI  - Protection against Metabolic Associated Fatty Liver Disease by Protocatechuic 
      Acid.
PG  - 2238959
LID - 10.1080/19490976.2023.2238959 [doi]
LID - 2238959
AB  - Gut microbiota-diet interaction has been identified as a key factor of metabolic 
      associated fatty liver disease (MAFLD). Recent studies suggested that dietary 
      polyphenols may protect against MAFLD by regulating gut microbiota; however, the 
      underlying mechanisms remain elusive. We first investigated the effects of 
      cyanidin 3-glucoside and its phenolic metabolites on high-fat diet induced MAFLD 
      in C57BL/6J mice, and protocatechuic acid (PCA) showed a significant positive 
      effect. Next, regulation of PCA on lipid metabolism and gut microbiota were 
      explored by MAFLD mouse model and fecal microbiota transplantation (FMT) 
      experiment. Dietary PCA reduced intraperitoneal and hepatic fat deposition with 
      lower levels of transaminases (AST & ALT) and inflammatory cytokines (IL-1beta, 
      IL-2, IL-6, TNF-alpha & MCP-1), but higher HDL-c/LDL-c ratio. Characterization of gut 
      microbiota indicated that PCA decreased the Firmicutes/Bacteroidetes ratio mainly 
      by reducing the relative abundance of genus Enterococcus, which was positively 
      correlated with the levels of LDL-c, AST, ALT and most of the up-regulated 
      hepatic lipids by lipidomics analysis. FMT experiments showed that Enterococcus 
      faecalis caused hepatic inflammation, fat deposition and insulin resistance with 
      decreased expression of carnitine palmitoyltransferase-1 alpha (CPT1alpha), which can 
      be reversed by PCA through inhibiting Enterococcus faecalis. Transcriptomics 
      analysis suggested that Enterococcus faecalis caused a significant decrease in 
      the expression of fibroblast growth factor 1 (Fgf1), and PCA recovered the 
      expression of Fgf1 with insulin-like growth factor binding protein 2 (Igfbp2), 
      insulin receptor substrate 1 (Irs1) and insulin receptor substrate 2 (Irs2). 
      These results demonstrated that high proportion of gut Enterococcus faecalis 
      accelerates MAFLD with decreased expression of CPT1alpha and Fgf1, which can be 
      prevented by dietary supplementation of PCA.
FAU - Tan, Jijun
AU  - Tan J
AD  - Hunan Collaborative Innovation Center for Utilization of Botanical Functional 
      Ingredients, College of Animal Science and Technology, Hunan Agricultural 
      University, Changsha, China.
FAU - Hu, Ruizhi
AU  - Hu R
AD  - Hunan Collaborative Innovation Center for Utilization of Botanical Functional 
      Ingredients, College of Animal Science and Technology, Hunan Agricultural 
      University, Changsha, China.
FAU - Gong, Jiatai
AU  - Gong J
AD  - Hunan Collaborative Innovation Center for Utilization of Botanical Functional 
      Ingredients, College of Animal Science and Technology, Hunan Agricultural 
      University, Changsha, China.
FAU - Fang, Chengkun
AU  - Fang C
AD  - Hunan Collaborative Innovation Center for Utilization of Botanical Functional 
      Ingredients, College of Animal Science and Technology, Hunan Agricultural 
      University, Changsha, China.
FAU - Li, Yanli
AU  - Li Y
AD  - Hunan Collaborative Innovation Center for Utilization of Botanical Functional 
      Ingredients, College of Animal Science and Technology, Hunan Agricultural 
      University, Changsha, China.
FAU - Liu, Ming
AU  - Liu M
AD  - Animal Science and Technology College, Beijing University of Agriculture, 
      Beijing, P. R China.
FAU - He, Ziyu
AU  - He Z
AD  - The United Graduate School of Agricultural Sciences, Faculty of Agriculture, 
      Kagoshima University, Kagoshima, Japan.
FAU - Hou, De-Xing
AU  - Hou DX
AD  - The United Graduate School of Agricultural Sciences, Faculty of Agriculture, 
      Kagoshima University, Kagoshima, Japan.
FAU - Zhang, Hongfu
AU  - Zhang H
AD  - State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese 
      Academy of Agricultural Sciences, Beijing, China.
FAU - He, Jianhua
AU  - He J
AD  - Hunan Collaborative Innovation Center for Utilization of Botanical Functional 
      Ingredients, College of Animal Science and Technology, Hunan Agricultural 
      University, Changsha, China.
FAU - Wu, Shusong
AU  - Wu S
AUID- ORCID: 0000-0003-3532-1165
AD  - Hunan Collaborative Innovation Center for Utilization of Botanical Functional 
      Ingredients, College of Animal Science and Technology, Hunan Agricultural 
      University, Changsha, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Gut Microbes
JT  - Gut microbes
JID - 101495343
RN  - 36R5QJ8L4B (protocatechuic acid)
RN  - 0 (Cholesterol, LDL)
RN  - 104781-85-3 (Fibroblast Growth Factor 1)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Cholesterol, LDL
MH  - Fibroblast Growth Factor 1/metabolism/pharmacology
MH  - *Gastrointestinal Microbiome
MH  - Mice, Inbred C57BL
MH  - *Non-alcoholic Fatty Liver Disease/etiology
MH  - Liver/metabolism
MH  - Diet, High-Fat/adverse effects
PMC - PMC10392757
OTO - NOTNLM
OT  - Enterococcus faecalis
OT  - gut microbiota
OT  - insulin
OT  - nonalcoholic fatty liver disease
OT  - protocatechuic acid
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2023/07/28 19:11
MHDA- 2023/07/28 19:12
PMCR- 2023/07/28
CRDT- 2023/07/28 12:13
PHST- 2023/07/28 19:12 [medline]
PHST- 2023/07/28 19:11 [pubmed]
PHST- 2023/07/28 12:13 [entrez]
PHST- 2023/07/28 00:00 [pmc-release]
AID - 2238959 [pii]
AID - 10.1080/19490976.2023.2238959 [doi]
PST - ppublish
SO  - Gut Microbes. 2023 Jan-Dec;15(1):2238959. doi: 10.1080/19490976.2023.2238959.