Why weight loss is only half the battle: the epigenetic memory of adipose tissue

Abstract

Section snippets

Context

Obesity is a major driver of chronic diseases, including type 2 diabetes, cardiovascular disease, and metabolic dysfunction-associated steatotic liver disease (MASLD), posing significant public health challenges¹. While weight loss (WL) through dietary, pharmacological, or surgical interventions offers metabolic improvements, sustaining these benefits is notoriously difficult due to the phenomenon of "yo-yo" or oscillatory weight rebound effect2, 3. Early studies attributed this phenomenon to

Objectives, Methods and Findings

The study analysed subcutaneous AT (scAT) and omental AT (omAT) biopsies from 18 lean individuals (who have never had obesity) and 20 individuals with obesity (without diabetes) before (T0) and 2 yr after (T1) bariatric surgery (BaS) from three independent studies⁹. Only those who achieved at least a 25% reduction in body mass index post-BaS (the WL cohort) were included. Despite no major differences in the snRNA-seq cellular composition between T0 and T1, a significant number of differentially

Significance of Findings

Collectively, these results indicate that prior nutritional states leave a lasting epigenetic imprint on adipocytes, influencing their future response to feeding and contributing to rebound obesity. Epigenetic changes, including histone modifications and chromatin accessibility, were key drivers of these differences, emphasizing how prior metabolic states can influence adipocyte function and promote long-term obesity outcomes.Notably, while these obesogenic imprints appear stable in AT, similar

Declaration of Competing Interest

None

Acknowledgement:

This work was supported by the National Medical Research Council (NMRC), Singapore (reference number: CIRG22jul-0025, NMRC/OFLCG/003/2018) and National Research Foundation, Singapore (ref number: NRF-CRP26-2021-0005).