Inhibition of glycosphingolipid synthesis reverses skin inflammation and hair loss in ApoE−/− mice fed western diet

Djahida Bedja, Wenwen Yan, Viren Lad, Domenica Iocco, Nickash Sivakumar, Veera Venkata Ratnam Bandaru, Subroto B Chatterjee

Research output: Contribution to journalArticle

Abstract

Sphingolipids have been accorded numerous biological functions however, the effects of feeding a western diet (diet rich in cholesterol and fat) on skin phenotypes, and color is not known. Here, we observed that chronic high-fat and high-cholesterol diet intake in a mouse model of atherosclerosis (ApoE−/−) decreases the level of ceramides and glucosylceramide. At the expense of increased levels of lactosylceramide due to an increase in the expression of lactosylceramide synthase (GalT-V). This is accompanied with neutrophil infiltration into dermis, and enrichment of tumor necrosis factor-stimulated gene-6 (TSG-6) protein. This causes skin inflammation, hair discoloration and loss, in ApoE−/− mice. Conversely, inhibition of glycosphingolipid synthesis, by D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), unbound or encapsulated in a biodegradable polymer (BPD) reversed these phenotypes. Thus, inhibition of glycosphingolipid synthesis represents a unique therapeutic approach relevant to human skin and hair Biology.

Original languageEnglish (US)
Article number11463
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Glycosphingolipids
Alopecia
Apolipoproteins E
Cholesterol
Glucosylceramides
Inflammation
Skin Pigmentation
Phenotype
Skin
Sphingolipids
Neutrophil Infiltration
Ceramides
High Fat Diet
Dermis
Hair
Atherosclerosis
Polymers
Tumor Necrosis Factor-alpha
Fats
Diet

ASJC Scopus subject areas

  • General

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Inhibition of glycosphingolipid synthesis reverses skin inflammation and hair loss in ApoE−/− mice fed western diet. / Bedja, Djahida; Yan, Wenwen; Lad, Viren; Iocco, Domenica; Sivakumar, Nickash; Bandaru, Veera Venkata Ratnam; Chatterjee, Subroto B.

In: Scientific Reports, Vol. 8, No. 1, 11463, 01.12.2018.

Research output: Contribution to journalArticle

Bedja, Djahida ; Yan, Wenwen ; Lad, Viren ; Iocco, Domenica ; Sivakumar, Nickash ; Bandaru, Veera Venkata Ratnam ; Chatterjee, Subroto B. / Inhibition of glycosphingolipid synthesis reverses skin inflammation and hair loss in ApoE−/− mice fed western diet. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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