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

Autor: Hinte LC; Laboratory of Nutrition and Metabolic Epigenetics, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Biomedicine Programme, Life Science Zurich Graduate School, Zurich, Switzerland., Castellano-Castillo D; Laboratory of Nutrition and Metabolic Epigenetics, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Medical Oncology Department, Virgen de la Victoria University Hospital, Málaga Biomedical Research Institute (IBIMA)-CIMES-UMA, Málaga, Spain., Ghosh A; Laboratory of Nutrition and Metabolic Epigenetics, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Functional Genomics Center Zurich, ETH Zurich and University Zurich, Zurich, Switzerland.; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland., Melrose K; Laboratory of Nutrition and Metabolic Epigenetics, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Biomedicine Programme, Life Science Zurich Graduate School, Zurich, Switzerland., Gasser E; Laboratory of Nutrition and Metabolic Epigenetics, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland., Noé F; Laboratory of Nutrition and Metabolic Epigenetics, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Functional Genomics Center Zurich, ETH Zurich and University Zurich, Zurich, Switzerland.; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland., Massier L; Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Zentrum München, University of Leipzig and University Hospital Leipzig, Leipzig, Germany., Dong H; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Stem Cell Bio Regenerative Med Institute, Stanford University, Stanford, CA, USA., Sun W; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Department of Bioengineering, Stanford University, Stanford, CA, USA., Hoffmann A; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Zentrum München, University of Leipzig and University Hospital Leipzig, Leipzig, Germany., Wolfrum C; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland., Rydén M; Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden., Mejhert N; Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden., Blüher M; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Zentrum München, University of Leipzig and University Hospital Leipzig, Leipzig, Germany.; Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany., von Meyenn F; Laboratory of Nutrition and Metabolic Epigenetics, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. ferdinand.vonmeyenn@hest.ethz.ch.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Nov 18. Date of Electronic Publication: 2024 Nov 18.
DOI: 10.1038/s41586-024-08165-7
Abstrakt: Reducing body weight to improve metabolic health and related comorbidities is a primary goal in treating obesity 1,2 . However, maintaining weight loss is a considerable challenge, especially as the body seems to retain an obesogenic memory that defends against body weight changes 3,4 . 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.
Competing Interests: Competing interests M.B. received honoraria as a consultant and speaker from Amgen, AstraZeneca, Bayer, Boehringer-Ingelhiem, Lilly, Novo Nordisk and Sanofi. M.R. received honoraria as a consultant and speaker from AstraZeneca, Boehringer-Ingelheim, Lilly, Novo Nordisk and Sanofi. The other authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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