Adipose tissue retains an epigenetic ‘memory’ of obesity, even after substantial weight loss. These lasting changes impair fat cell function and heighten susceptibility to weight regain, potentially contributing to the ‘yo-yo’ effect. Targeting this memory could be key to achieving lasting metabolic health and improved longevity.
November 2024 – Nature
Key takeaways
- Obesity leaves a lasting cellular imprint: Fat tissue maintains transcriptional and epigenetic changes even after substantial weight loss, particularly within adipocytes. These changes are not fully reversed by weight loss, suggesting that obesity leaves a cellular memory that continues to influence fat cell function and metabolic health long-term
- Adipocytes are primed for dysfunction: Following weight loss, formerly obese adipocytes exhibit impaired metabolic gene expression and increased markers of inflammation and fibrosis. This persistent dysfunction may compromise fat tissue’s ability to maintain healthy metabolic processes and increase vulnerability to chronic disease as people age
- Epigenetic alterations drive weight regain: Mice that previously experienced obesity showed faster weight regain and stronger metabolic disruption when re-exposed to a high-fat diet. These effects were underpinned by persistent epigenetic modifications in fat cells, including changes in histone markers and chromatin accessibility that predispose to inflammation and impaired adipogenesis
- New therapeutic targets for weight stability: By identifying epigenetic marks linked to obesogenic memory, this research opens up potential strategies to disrupt this memory and promote long-term weight stability. Such interventions could improve healthspan by supporting better metabolic function and reducing the cyclical burden of weight loss and regain
Read the article at: Hinte, Laura C., et al. “Adipose tissue retains an epigenetic memory of obesity after weight loss.” Nature, vol. 636, 2024, pp. 457–465. https://doi.org/10.1038/s41586-024-08165-7
