PUBLICATION

Esculetin Alleviates Nonalcoholic Fatty Liver Disease on High-Cholesterol-Diet-Induced Larval Zebrafish and FFA-Induced BRL-3A Hepatocyte

Authors

Ma, J., Deng, Y., Yang, T., Li, M., Shang, J.

ID

ZDB-PUB-230122-23

Date

2023

Source

International Journal of Molecular Sciences 24(2): (Journal)

Registered Authors

Li, Maoru, Ma, Ji, Shang, Jing

Keywords

antioxidant, esculetin, lipid-lowering, non-alcoholic fatty liver disease

MeSH Terms

Animals
Cholesterol/metabolism
Diet, High-Fat
Hepatocytes/metabolism
Hypercholesterolemia*/metabolism
Larva
Liver/metabolism
Non-alcoholic Fatty Liver Disease*/metabolism
Zebrafish

(all 9)

PubMed

36675107 Full text @ Int. J. Mol. Sci.

Abstract

Non-alcoholic fatty liver disease (NAFLD), defined in recent years as metabolic-associated fatty liver disease (MAFLD), is one of the most common liver diseases in the world, with no drugs on market. Esculetin (ESC) is an active compound discovered in a variety of natural products that modulates a wide range of metabolic diseases and is a potential drug for the treatment of NAFLD. In this study, we used an HCD-induced NAFLD larval zebrafish model in vivo and an FFA-induced BRL-3A hepatocyte model in vitro to evaluate the anti-NAFLD effect of ESC. Lipid lowering, anti-oxidation and anti-inflammation effects were revealed on ESC and related gene changes were observed. This study provides a reference for further study and development of ESC as a potential anti-NAFLD/MAFLD drug.

Genes / Markers

Marker	Marker Type	Name
cpt1aa	GENE	carnitine palmitoyltransferase 1Aa (liver)
fasn	GENE	fatty acid synthase
il1b	GENE	interleukin 1, beta
il6	GENE	interleukin 6 (interferon, beta 2)
keap1a	GENE	kelch-like ECH-associated protein 1a
mmp9	GENE	matrix metallopeptidase 9
nfe2l2a	GENE	nfe2 like bZIP transcription factor 2a
ppardb	GENE	peroxisome proliferator-activated receptor delta b
pparg	GENE	peroxisome proliferator-activated receptor gamma
srebf1	GENE	sterol regulatory element binding transcription factor 1

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Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
cpt1aa	AB	high cholesterol	Days 21-29	whole organism	RTPCR	Figure 3
cpt1aa	AB	high cholesterol, chemical treatment by environment: esculetin	Days 21-29	whole organism	RTPCR	Figure 3
fasn	AB	high cholesterol	Days 21-29	whole organism	RTPCR	Figure 3
fasn	AB	high cholesterol, chemical treatment by environment: esculetin	Days 21-29	whole organism	RTPCR	Figure 3
il1b	AB	high cholesterol, chemical treatment by environment: esculetin	Days 21-29	whole organism	RTPCR	Figure 3
il1b	AB	high cholesterol	Days 21-29	whole organism	RTPCR	Figure 3
il6	AB	high cholesterol, chemical treatment by environment: esculetin	Days 21-29	whole organism	RTPCR	Figure 3
il6	AB	high cholesterol	Days 21-29	whole organism	RTPCR	Figure 3
ppardb	AB	high cholesterol	Days 21-29	whole organism	RTPCR	Figure 3
ppardb	AB	high cholesterol, chemical treatment by environment: esculetin	Days 21-29	whole organism	RTPCR	Figure 3

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB	high cholesterol	Days 21-29	gut lipid increased amount, abnormal	Figure 1
AB	high cholesterol	Days 21-29	liver fatty, abnormal	Figure 1
AB	high cholesterol	Days 21-29	whole organism cpt1aa expression decreased amount, abnormal	Figure 3
AB	high cholesterol	Days 21-29	whole organism fasn expression increased amount, abnormal	Figure 3
AB	high cholesterol	Days 21-29	whole organism il1b expression increased amount, abnormal	Figure 3
AB	high cholesterol	Days 21-29	whole organism il6 expression increased amount, abnormal	Figure 3
AB	high cholesterol	Days 21-29	whole organism ppardb expression decreased amount, abnormal	Figure 3
AB	high cholesterol	Days 21-29	whole organism pparg expression decreased amount, abnormal	Figure 3
AB	high cholesterol	Days 21-29	whole organism srebf1 expression increased amount, abnormal	Figure 3
AB	high cholesterol	Days 21-29	whole organism tnfa expression increased amount, abnormal	Figure 3

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Mutations / Transgenics

Human Disease / Model

Human Disease	Fish	Conditions	Evidence
metabolic dysfunction-associated steatotic liver disease	AB	high cholesterol	TAS

Sequence Targeting Reagents

Fish

Fish
AB

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Ma et al., 2023 ZDB-PUB-230122-23 PMID:36675107

Esculetin Alleviates Nonalcoholic Fatty Liver Disease on High-Cholesterol-Diet-Induced Larval Zebrafish and FFA-Induced BRL-3A Hepatocyte

Ma et al., 2023

ZDB-PUB-230122-23
PMID:36675107