The management of obesity involves substantial weight loss through different types of interventions (dietary, lifestyle, pharmaceutical and surgery), but one of its challenges is that individuals tend to regain weight over time. Why exactly this return to obesity occurs is not understood. Metabolic and transcriptional memory has been previously reported in some mouse and human cell types, and it is expected that epigenetic mechanisms play a part in such memory. But most human studies have focused on analyses in bulk tissues or whole blood, so it remains unclear whether individual cells retain a metabolic memory, and the underlying mechanisms. In a recent study that uses single-nucleus RNA sequencing (snRNA-seq), von Meyenn and colleagues found that human and mouse adipose tissues retain transcriptional patterns after weight loss and that, in mouse adipocytes, obesity-induced epigenetic alterations persisted and negatively affected their function.

Transcriptional changes during obesity were most pronounced in adipocytes, adipose progenitor cells and endothelial cells, and adipocytes consistently retained those changes from T0 to T1. In adipocytes, pathways linked to adipocyte metabolism and function were persistently downregulated, whereas pathways linked to fibrosis and apoptosis were persistently upregulated. These results indicate that obesity induces transcriptional (obesogenic) changes in adipocytes and that these changes are maintained following substantial weight loss.