Core Viewpoint - The article discusses a recent study published in *Nature* by a team from ETH Zurich, which reveals that the transcriptional changes in fat cells during obesity persist even two years after successful weight loss, indicating a phenomenon referred to as "fat memory" [7][11][22]. Group 1: Research Findings - The study analyzed fat tissue samples from participants who underwent weight loss surgery, showing that many differentially expressed genes (DEGs) during obesity remained dysregulated two years post-weight loss [11][13]. - In mouse experiments, previously obese mice exhibited a significantly enhanced ability to absorb sugars and fats, leading to faster weight regain when re-exposed to a high-fat diet [8][24]. - The research found that the longer the duration of obesity, the poorer the recovery of gene expression post-weight loss, suggesting that "fat memory" is influenced by the duration of obesity [21][25]. Group 2: Cellular and Molecular Mechanisms - Single-nucleus RNA sequencing revealed that the composition of cell types in the fat tissue did not change significantly between the time points, but many obesity-related DEGs remained altered [13][20]. - The study highlighted that the transcriptional dysregulation was most pronounced in adipocytes, adipocyte progenitor cells, and endothelial cells, with downregulation of fat metabolism pathways and upregulation of fibrosis and apoptosis-related pathways [14][20]. - The findings suggest that epigenetic changes account for 57-62% of downregulated DEGs and 68-75% of upregulated DEGs, indicating that epigenetic mechanisms play a crucial role in "fat memory" [22].