PXD030954

PXD030954 is an original dataset announced via ProteomeXchange.

Title	Liver Proteomic Profile in Mice on a High-Fat Diet
Description	Nonalcoholic fatty liver disease (NAFLD) is becoming a primary cause of liver damage in Western society. Nonalcoholic steatohepatitis (NASH) is an advanced stage of NAFLD and may lead to liver cancer. Our previous long-term murine studies have shown the beneficial role of Aquamin, a red marine algae-derived (calcium, magnesium, additional trace elements-rich) supplement, in reducing liver injury and decreasing liver tumor incidence. The main objective of the study was to determine how manifestations and effects of NASH can be mitigated using Aquamin. We hypothesized that mice on a high-fat Western diet (HFWD) with minerals would exhibit less liver injury than mice on a HFWD without minerals. Methods: Two cohorts of MS-NASH mice (8-week-old) were placed on a HFWD with and without minerals for 16 weeks. An additional cohort of MS-NASH mice on the same HFWD was treated with obeticholic acid (OCA). C57BL/6 mice on a regular chow were included as a control. During the in-life phase of the study, weight changes were assessed weekly. At termination, livers were histologically assessed for steatosis and fibrosis by using hematoxylin and eosin, and picrosirius red staining. Liver tissue samples were also subjected to tandem mass tag (TMT) mass-spectroscopic proteomics for protein expression profile in individual mice. Results: Mice on HFWD gained more weight than mice on control diet, but there was no overall change in weight for mice on HFWD, irrespective of interventions. On histological assessment, there was no difference in steatosis between the two high-fat groups, but mice on Aquamin showed reduced picrosirius red staining or collagen deposition as compared to placebo on HFWD mice. Regarding proteomic profile, there was a clear distinction among control and HFWD groups. Placebo (on HFWD) mice were used for comparison. Aquamin intervention altered 91 proteins while OCA altered 84 proteins in liver samples with a 2-fold change. Of these, 57 proteins were common between Aquamin and OCA. Most of the proteins were upregulated. Aquamin upregulated 39 unique pathways (with a p-value <0.05) as assessed by the Reactome database. Some of the pathways significantly impacted by Aquamin were formation of cornified envelope; keratinization; gap junction assembly; type I hemidesmosome assembly; apoptosis-related; plasma lipoprotein assembly, remodeling and clearance; and hedgehog “off” state pathways. Proteins downregulated by OCA are mainly involved in the synthesis of bile acids and bile salts. Conclusion: The addition of dietary minerals may play a protective role in interfering with downstream advancement from steatosis to NASH. Our studies provide mechanistic insight into how mineral supplementation may contribute to the reduction in liver injury and tumor formation (one of the most devastating consequences) of fatty liver disease in the context of HFWD-induced steatosis.
HostingRepository	PRIDE
AnnounceDate	2022-06-02
AnnouncementXML	Submission_2022-06-02_05:57:19.997.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Muhammad Aslam
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-14 00:50:53	ID requested
⏵ 1	2022-06-02 05:57:20	announced

Varani J, McClintock SD, Knibbs RN, Harber I, Zeidan D, Jawad-Makki MAH, Aslam MN, Liver Protein Expression in NASH Mice on a High-Fat Diet: Response to Multi-Mineral Intervention. Front Nutr, 9():859292(2022) [pubmed]

submitter keyword: Liver Cancer, NASH, NAFLD, minerals, high fat, CCN3

Muhammad N Aslam
contact affiliation	Department of Pathology The University of Michigan 1150 W Medical Center Dr Ann Arbor, MI 48109, USA
contact email	mnaslam@med.umich.edu
lab head
Muhammad Aslam
contact affiliation	University of Michigan
contact email	mnaslam@umich.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030954
     1. Label: PRIDE project
     2. Name: Liver Proteomic Profile in Mice on a High-Fat Diet