Dehydroabietic acid alleviates high fat diet-induced insulin resistance and hepatic steatosis through dual activation of PPAR-γ and PPAR-α.

Xie, Z; Gao, G; Wang, H; Li, E; Yuan, Y; Xu, J; Zhang, Z; Wang, P; Fu, Y; Zeng, H; Song, J; Hölscher, C; Chen, H

Dehydroabietic acid alleviates high fat diet-induced insulin resistance and hepatic steatosis through dual activation of PPAR-γ and PPAR-α.

Xie, Z Gao, G Wang, H Li, E Yuan, Y Xu, J Zhang, Z Wang, P Fu, Y Zeng, H Song, J Hölscher, C Chen, H

Permalink

Publisher:: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Publication Type:: Journal Article
Citation:: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2020, 127
Issue Date:: 2020-07

Open Access

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is open access.

The embargo period expires on 1 Jul 2022

Adobe PDF

Download Published VersionAdobe PDF (4.4 MB)

View on publisher's site

View statistics

Full metadata record

Field	Value	Language
dc.contributor.author	Xie, Z
dc.contributor.author	Gao, G
dc.contributor.author	Wang, H
dc.contributor.author	Li, E
dc.contributor.author	Yuan, Y
dc.contributor.author	Xu, J
dc.contributor.author	Zhang, Z
dc.contributor.author	Wang, P
dc.contributor.author	Fu, Y
dc.contributor.author	Zeng, H
dc.contributor.author	Song, J
dc.contributor.author	Hölscher, C
dc.contributor.author	Chen, H https://orcid.org/0000-0001-6883-3752
dc.date.accessioned	2020-11-17T02:46:01Z
dc.date.available	2020-04-08
dc.date.available	2020-11-17T02:46:01Z
dc.date.issued	2020-07
dc.identifier.citation	Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2020, 127
dc.identifier.issn	0753-3322
dc.identifier.issn	1950-6007
dc.identifier.uri	http://hdl.handle.net/10453/144082
dc.description.abstract	Dual-PPAR-α/γ agonist has the dual potentials to improve insulin resistance (IR) and hepatic steatosis associated with obesity. This study aimed to investigate whether dehydroabietic acid (DA), a naturally occurred compound, can bind to and activate both PPAR-γ and PPAR-α to ameliorate IR and hepatic steatosis in high-fat diet (HFD)-fed mice.. We found that DA formed stable hydrogen bonds with the ligand-binding domains of PPAR-γ and PPAR-α. DA treatment also promoted 3T3-L1 differentiation via PPAR-γ activation, and mitochondrial oxygen consumption in HL7702 cells via PPAR-α activation. In HFD-fed mice, DA treatment alleviated glucose intolerance and IR, and reduced hepatic steatosis, liver injury markers (ALT, AST), and lipid accumulation, and promoted mRNA expression of PPAR-γ and PPAR-α signaling elements involved in IR and lipid metabolism in vivo and in vitro, and inhibited mRNA expression of pro-inflammatory factors. Therefore, DA is a dual-PPAR-α/γ and PPAR-γ partial agonist, which can attenuate IR and hepatic steatosis induced by HFD-consumption in mice.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
dc.relation.ispartof	Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
dc.relation.isbasedon	10.1016/j.biopha.2020.110155
dc.rights	info:eu-repo/semantics/embargoedAccess
dc.subject	1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	Oncology & Carcinogenesis
dc.title	Dehydroabietic acid alleviates high fat diet-induced insulin resistance and hepatic steatosis through dual activation of PPAR-γ and PPAR-α.
dc.type	Journal Article
utslib.citation.volume	127
utslib.location.activity	France
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
utslib.copyright.embargo	2022-07-01T00:00:00+1000Z
dc.date.updated	2020-11-17T02:45:55Z
pubs.publication-status	Published
pubs.volume	127

Abstract:

Dual-PPAR-α/γ agonist has the dual potentials to improve insulin resistance (IR) and hepatic steatosis associated with obesity. This study aimed to investigate whether dehydroabietic acid (DA), a naturally occurred compound, can bind to and activate both PPAR-γ and PPAR-α to ameliorate IR and hepatic steatosis in high-fat diet (HFD)-fed mice.. We found that DA formed stable hydrogen bonds with the ligand-binding domains of PPAR-γ and PPAR-α. DA treatment also promoted 3T3-L1 differentiation via PPAR-γ activation, and mitochondrial oxygen consumption in HL7702 cells via PPAR-α activation. In HFD-fed mice, DA treatment alleviated glucose intolerance and IR, and reduced hepatic steatosis, liver injury markers (ALT, AST), and lipid accumulation, and promoted mRNA expression of PPAR-γ and PPAR-α signaling elements involved in IR and lipid metabolism in vivo and in vitro, and inhibited mRNA expression of pro-inflammatory factors. Therefore, DA is a dual-PPAR-α/γ and PPAR-γ partial agonist, which can attenuate IR and hepatic steatosis induced by HFD-consumption in mice.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/144082