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Duteil, D.* ; Tosic, M.* ; Willmann, D.* ; Georgiadi, A. ; Kanouni, T.* ; Schuele, R.*

Lsd1 prevents age-programed loss of beige adipocytes.

Proc. Natl. Acad. Sci. U.S.A. 114, 5265-5270 (2017)
Publ. Version/Full Text Research data DOI
Aging is accompanied by major changes in adipose tissue distribution and function. In particular, with time, thermogenic-competent beige adipocytes progressively gain a white adipocyte morphology. However, the mechanisms controlling the age-related transition of beige adipocytes to white adipocytes remain unclear. Lysine-specific demethylase 1 (Lsd1) is an epigenetic eraser enzyme positively regulating differentiation and function of adipocytes. Here we show that Lsd1 levels decrease in aging inguinal white adipose tissue concomitantly with beige fat cell decline. Accordingly, adipocyte-specific increase of Lsd1 expression is sufficient to rescue the age-related transition of beige adipocytes to white adipocytes in vivo, whereas loss of Lsd1 precipitates it. Lsd1 maintains beige adipocytes by controlling the expression of peroxisome proliferator-activated receptor a (Ppara), and treatment with a Ppara agonist is sufficient to rescue the loss of beige adipocytes caused by Lsd1 ablation. In summary, our data provide insights into the mechanism controlling the age-related beige-to-white adipocyte transition and identify Lsd1 as a regulator of beige fat cell maintenance.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Aging ; Lsd1 ; Adipocyte ; Ppara ; Beige Fat; White Adipose-tissue; Activated-receptor-alpha; Brown Adipocytes; Transcription; Cells; Mice; Adipogenesis; Distinct; Origins; Lineage
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 114, Issue: 20, Pages: 5265-5270 Article Number: , Supplement: ,
Publisher National Academy of Sciences
Publishing Place Washington
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Cancer (IDC)