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Taege, N.* ; Britsemmer, J.H.* ; Israel, A. ; Krause, C.* ; Junge, S.* ; Feuchtinger, A. ; Ussar, S. ; Pfluger, P.T. ; Gemoll, T.* ; Schriever, S.C. ; Kirchner, H.*

A Novel mechanism for depot-specific leptin gene expression regulation and its persistence after weight loss.

iScience 29:115101 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Leptin gene (Lep) expression correlates with fat mass but differs between epididymal and inguinal fat depots in obesity. We investigated whether DNA methylation of a Lep enhancer (RS1) and the long non-coding RNA lncOb epigenetically regulate this depot-specific expression. We analyzed DNA methylation, Lep and lncOb expression in fat depots across metabolic states in male C57BL/6 mice using CRISPR-dCas9-KRAB-mediated repression, methylation-sensitive luciferase assays, and mass spectrometry. Under obesogenic conditions, RS1 methylation increased specifically in hypertrophic adipocytes of epididymal fat, repressing Lep transcription. This methylation persisted after long-term weight loss. LncOb expression correlated with Lep levels but was reduced in epididymal fat during obesity and remained suppressed post-weight loss. Together, our findings demonstrate that adipocyte Lep expression is dynamically regulated by depot-specific epigenetic mechanisms that become dysregulated in obesity and resist reversal by weight loss, providing a unifying molecular mechanism for depot-specific Lep expression differences in a state of obesity.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Human Metabolism ; Epigenetics; Visceral Adipose-tissue; Adipocyte Size; Fat Depots; Obesity; Mouse; Resistance; Secretion; Insulin; Risk
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Journal iScience
Quellenangaben Volume: 29, Issue: 4, Pages: , Article Number: 115101 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Reviewing status Peer reviewed
Institute(s) Adipocytes & Metabolism (ADM)
CF Pathology & Tissue Analytics (CF-PTA)
Institute of Diabetes and Obesity (IDO)
Grants German Research Foundation DFG
European Research Council ERC-CoG Yoyo-LepReSens