Fat cells have long-lasting (epigenetic) memory

Treating obesity requires significant weight loss through various types of interventions (diet, lifestyle, medication, and surgery). However, one of the challenges is that people tend to gain weight back over time. Exactly why this return to obesity occurs is not clear. Metabolic and transcriptional memory have already been reported in some mouse and human cell types, and epigenetic mechanisms are expected to play a role in this memory. However, most human studies have focused on analyzes in large tissues or whole blood, so it remains unclear whether individual cells retain metabolic memory and the underlying mechanisms. In a recent study using single nuclear RNA sequencing (snRNA-seq), von Meyenn and colleagues found that adipose tissue from humans and mice retained transcription patterns after weight loss and that obesity-induced epigenetic changes persisted in adipocytes from mice their function was negatively affected.

Transcriptional changes during obesity were most pronounced in adipocytes, adipose progenitor cells, and endothelial cells, and adipocytes consistently maintained these changes from T0 to T1. In adipocytes, signaling pathways associated with adipocyte metabolism and function were persistently downregulated, while signaling pathways associated with fibrosis and apoptosis were persistently upregulated. These results suggest that obesity induces transcriptional (obesogenic) changes in adipocytes and that these changes persist after significant weight loss.