PXD040233

PXD040233 is an original dataset announced via ProteomeXchange.

Title	Bicyclol attenuates high fat diet-induced nonalcoholic fatty liver disease/nonalcoholic steatohepatitis through modulating multiple pathways in mice.
Description	The pathological progression of nonalcoholic fatty liver disease (NAFLD) is driven by multiple factors, and nonalcoholic steatohepatitis (NASH) represents its progressive form. In our previous studies, we found that bicyclol had beneficial effects on NAFLD/NASH. Here we aim to investigate the underlying molecular mechanisms of the bicyclol effect on NAFLD/NASH induced by high-fat diet (HFD) feeding. A mice model of NAFLD/NASH induced by HFD-feeding for 8 weeks was used. As a pretreatment, bicyclol (200 mg/kg) was given to mice by oral gavage twice daily. Hematoxylin and eosin (H&E) stains were processed to evaluate hepatic steatosis, and hepatic fibrous hyperplasia was assessed by Masson staining. Biochemistry analyses were used to measure serum aminotransferase, serum lipids, and lipids in liver tissues. Proteomics and bioinformatics analyses were performed to identify the signaling pathways and target proteins. The real-time RT-PCR and Western blot analyses were performed to verify the proteomics data. As a result, bicyclol had a markedly protective effect against NAFLD/NASH by suppressing the increase of serum aminotransferase, hepatic lipid accumulation and alleviating histopathological changes in liver tissues. Proteomics analyses showed that bicyclol remarkably restored major pathways related to immunological responses and metabolic processes altered by HFD feeding. Consistent with our previous results, bicyclol significantly inhibited inflammation and oxidative stress pathway related indexes (SAA1, GSTM1 and RDH11). Furthermore, the beneficial effects of bicyclol were closely associated with the signaling pathways of bile acid metabolism (NPC1, SLCOLA4 and UGT1A1), cytochrome P450-mediated metabolism (CYP2C54, CYP2C70 and CYP3A25), biological processes such as metal ion metabolism (Ceruloplasmin and Metallothionein-1), angiogenesis (ALDH1A1) and immunological responses (IFI204 and IFIT3). These findings suggested that bicyclol is a potential preventive agent for NAFLD/NASH by targeting multiple mechanisms in future clinical investigations.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:00:06.246.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD040233
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Benhong Xu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-17 04:11:14	ID requested
1	2023-03-23 02:49:19	announced
⏵ 2	2023-11-14 09:00:06	announced	2023-11-14: Updated project metadata.

10.6019/PXD040233;

submitter keyword: Bicyclol, Multiple pathways, Proteomics, NAFLD, NASH

Benhong Xu
contact affiliation	Shenzhen Center for Disease Control and Prevention
contact email	xubenhong@szcdc.net
lab head
Benhong Xu
contact affiliation	Shenzhen Center for Disease Control and Prevention
contact email	xubenhong@szcdc.net
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040233
     1. Label: PRIDE project
     2. Name: Bicyclol attenuates high fat diet-induced nonalcoholic fatty liver disease/nonalcoholic steatohepatitis through modulating multiple pathways in mice.