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Hinte, L.C.* ; Castellano-Castillo, D.* ; Ghosh, A.* ; Melrose, K.* ; Gasser, E.* ; Noé, F.* ; Massier, L. ; Dong, H.* ; Sun, W.* ; Hoffmann, A. ; Wolfrum, C.* ; Rydén, M.* ; Mejhert, N.* ; Blüher, M. ; von Meyenn, F.*

Adipose tissue retains an epigenetic memory of obesity after weight loss.

Nature, DOI: 10.1038/s41586-024-08165-7 (2024)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Reducing body weight to improve metabolic health and related comorbidities is a primary goal in treating obesity1,2. However, maintaining weight loss is a considerable challenge, especially as the body seems to retain an obesogenic memory that defends against body weight changes3,4. Overcoming this barrier for long-term treatment success is difficult because the molecular mechanisms underpinning this phenomenon remain largely unknown. Here, by using single-nucleus RNA sequencing, we show that both human and mouse adipose tissues retain cellular transcriptional changes after appreciable weight loss. Furthermore, we find persistent obesity-induced alterations in the epigenome of mouse adipocytes that negatively affect their function and response to metabolic stimuli. Mice carrying this obesogenic memory show accelerated rebound weight gain, and the epigenetic memory can explain future transcriptional deregulation in adipocytes in response to further high-fat diet feeding. In summary, our findings indicate the existence of an obesogenic memory, largely on the basis of stable epigenetic changes, in mouse adipocytes and probably other cell types. These changes seem to prime cells for pathological responses in an obesogenic environment, contributing to the problematic 'yo-yo' effect often seen with dieting. Targeting these changes in the future could improve long-term weight management and health outcomes.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Insulin-resistance; Bariatric Surgery; Dna Methylation; Gene-expression; Chromatin; Identity; Package; Brown
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Zeitschrift Nature
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Förderungen European Foundation for the Study of Diabetes
European Research Council Starting Grant
Basel Research Centre for Child Health (Multi-Investigator Project 2020)
Deutsche Forschungsgemeinschaft
Margareta af Ugglas foundation
Swedish Research Council
European Research Council Synergy Grant
Novo Nordisk Foundation
Knut and Alice Wallenberg's Foundation (Wallenberg Clinical Scholar)
Center for Innovative Medicine
Swedish Society for Medical Research
Swedish Diabetes Foundation
Stockholm County Council
Strategic Research Program in Diabetes at Karolinska Institutet
ETH Zurich core funding