PXD013423-2

PXD013423 is an original dataset announced via ProteomeXchange.

Title	Hepatocyte Deletion of Triglyceride-Synthesis Enzyme DGAT2 Reduces Steatosis without Increasing Inflammation or Fibrosis
Description	Non-alcoholic fatty liver disease (NAFLD) is characterized by excess lipid accumulation in hepatocytes and reprepresents a huge public health problem owing to its propensity to progress to non-alcoholic steatohepatitis (NASH), fibrosis, and liver failure. The lipids stored in hepatic steatosis are primarily triglycerides (TGs) synthesized by two acyl CoA:diacylglycerol acyltransferase (DGAT) enzymes. Either DGAT1 or DGAT2 catalyzes this reaction, and these enzymes have been suggested to differentially utilize exogenous or endogenously synthesized fatty acids, with DGAT2 being linked to storage of fatty acids from de novo lipogenesis, a process that is increased in NAFLD. However, whether DGAT2 is more responsible for lipid accumulation in NAFLD and the progression to fibrosis is currently unknown. Also, it is unresolved whether DGAT2 can be safely inhibited as a therapy for NAFLD. Here we induced NAFLD-like disease in mice by feeding a diet rich in fructose, saturated fat, and cholesterol and found that hepatocyte-specfici Dgat2 deficiency reduced expression of de novo lipogenesis genes and lowered liver TGs by ~70%. Importantly, the reduction of steatosis was not accompanied by increased inflammation or fibrosis, and insulin and glucose metabolism were unchanged. Conclusion: This study suggests that hepatic DGAT2 deficiency successfully reduced diet-induced hepatic steatosis and supports the development of DGAT2 inhibitors as a therapeutic strategy for treating NAFLD and preventing downstream consequences.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:05:16.234.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zon Weng Lai
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-04-09 04:08:53	ID requested
1	2020-05-26 14:04:15	announced
⏵ 2	2024-10-22 05:05:17	announced	2024-10-22: Updated project metadata.

10.1002/hep.30765;

Gluchowski NL, Gabriel KR, Chitraju C, Bronson RT, Mejhert N, Boland S, Wang K, Lai ZW, Farese RV, Walther TC, Hepatocyte Deletion of Triglyceride-Synthesis Enzyme Acyl CoA: Diacylglycerol Acyltransferase 2 Reduces Steatosis Without Increasing Inflammation or Fibrosis in Mice. Hepatology, 70(6):1972-1985(2019) [pubmed]

submitter keyword: Triacylglycerol, liver, diacylglycerol, nonalcoholic fatty liver disease, steatohepatitis, dietary lipids

Tobias Walther
contact affiliation	Harvard T. H. Chan School of Public Health
contact email	twalther@hsph.harvard.edu
lab head
Zon Weng Lai
contact affiliation	Harvard T. H. Chan School of Public Health
contact email	zlai@hsph.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013423
     1. Label: PRIDE project
     2. Name: Hepatocyte Deletion of Triglyceride-Synthesis Enzyme DGAT2 Reduces Steatosis without Increasing Inflammation or Fibrosis