دورية أكاديمية
أعرض في EDS

Ligand dependent interaction between PC-TP and PPARδ mitigates diet-induced hepatic steatosis in male mice.

التفاصيل البيبلوغرافية
العنوان: Ligand dependent interaction between PC-TP and PPARδ mitigates diet-induced hepatic steatosis in male mice.
المؤلفون: Druzak SA; Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, USA., Tardelli M; Joan & Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Mays SG; Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, USA., El Bejjani M; Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, USA., Mo X; Department of Chemical Biology and Pharmacology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, USA., Maner-Smith KM; Emory Integrated Lipidomics and Metabolomics Core, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, USA., Bowen T; Emory Integrated Lipidomics and Metabolomics Core, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, USA., Cato ML; Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, USA., Tillman MC; Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, USA., Sugiyama A; Joan & Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, NY, USA.; Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Xie Y; Joan & Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, NY, USA.; Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Fu H; Department of Chemical Biology and Pharmacology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, USA., Cohen DE; Joan & Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, NY, USA.; Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Ortlund EA; Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, USA. eortlun@emory.edu.
المصدر: Nature communications [Nat Commun] 2023 May 12; Vol. 14 (1), pp. 2748. Date of Electronic Publication: 2023 May 12.
نوع المنشور: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: PPAR delta*/genetics , Fatty Liver*/genetics , Fatty Liver*/prevention & control , Fatty Liver*/metabolism, Male ; Animals ; Mice ; Phosphatidylcholines/metabolism ; Ligands ; Liver/metabolism ; Diet
مستخلص: Phosphatidylcholine transfer protein (PC-TP; synonym StarD2) is a soluble lipid-binding protein that transports phosphatidylcholine (PC) between cellular membranes. To better understand the protective metabolic effects associated with hepatic PC-TP, we generated a hepatocyte-specific PC-TP knockdown (L-Pctp -/- ) in male mice, which gains less weight and accumulates less liver fat compared to wild-type mice when challenged with a high-fat diet. Hepatic deletion of PC-TP also reduced adipose tissue mass and decreases levels of triglycerides and phospholipids in skeletal muscle, liver and plasma. Gene expression analysis suggest that the observed metabolic changes are related to transcriptional activity of peroxisome proliferative activating receptor (PPAR) family members. An in-cell protein complementation screen between lipid transfer proteins and PPARs uncovered a direct interaction between PC-TP and PPARδ that was not observed for other PPARs. We confirmed the PC-TP- PPARδ interaction in Huh7 hepatocytes, where it was found to repress PPARδ-mediated transactivation. Mutations of PC-TP residues implicated in PC binding and transfer reduce the PC-TP-PPARδ interaction and relieve PC-TP-mediated PPARδ repression. Reduction of exogenously supplied methionine and choline reduces the interaction while serum starvation enhances the interaction in cultured hepatocytes. Together our data points to a ligand sensitive PC-TP- PPARδ interaction that suppresses PPAR activity.
(© 2023. The Author(s).)
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معلومات مُعتمدة: F31 DK126435 United States DK NIDDK NIH HHS; T32 GM008602 United States GM NIGMS NIH HHS; R01 DK048873 United States DK NIDDK NIH HHS; T32 GM008367 United States GM NIGMS NIH HHS; UL1 TR002378 United States TR NCATS NIH HHS
المشرفين على المادة: 0 (PPAR delta)
0 (Phosphatidylcholines)
0 (Ligands)
تواريخ الأحداث: Date Created: 20230512 Date Completed: 20230515 Latest Revision: 20230612
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10182070
DOI: 10.1038/s41467-023-38010-w
PMID: 37173315
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-023-38010-w