重磅揭秘！《自然》解析：减肥如何彻底改变你体内的“脂肪世界”？

Core Viewpoint - The article discusses the significant health risks associated with obesity, emphasizing that abdominal fat is a "hidden killer" linked to various metabolic diseases. It highlights the potential for rapid health improvements through weight loss and presents new research that uncovers the cellular changes in adipose tissue during obesity and subsequent weight loss [6][18]. Group 1: Fat Tissue Remodeling Overview - A comprehensive single-cell atlas of adipose tissue was constructed, analyzing over 171,000 cells from 25 severely obese individuals (pre- and post-weight loss) and 24 healthy individuals, focusing on abdominal subcutaneous fat. The analysis revealed an influx of immune cells in obese adipose tissue and a significant reduction in mature adipocyte proportions, indicating cell death or insufficient renewal. Weight loss effectively alleviated these pathological changes [8][10]. Group 2: Macrophage "Memory Effect" - In obesity, the proportion of macrophages in adipose tissue increased from 14% to 31%, primarily comprising lipid-associated macrophages (LAMs). These macrophages exhibited a globally activated metabolic state. Post-weight loss, macrophage numbers decreased to 18%, and inflammatory gene expression significantly downregulated, although the metabolic activation state did not fully revert, suggesting a potential "epigenetic memory" [10][12]. Group 3: Adipocyte Metabolism "Reboot" - Eight subtypes of mature adipocytes were identified, with stress-type and fibrotic-type cells significantly increasing in obese individuals, while lipid-synthesis-type cells decreased. Weight loss led to a substantial reduction in stress-type cells and a normalization of lipid-synthesis-type cells. Metabolic pathway analysis indicated that weight loss enhanced global metabolic flux in adipocytes, potentially improving insulin sensitivity [12][14]. Group 4: Decline of Multi-Cellular "Stress Ecological Niche" - The proportion of stress-type adipose precursor cells (APCs) increased in obese individuals, while weight loss significantly reduced these and fibrotic-type APCs. The vascular system also showed stress-type subpopulations, which were diminished post-weight loss, indicating a reversal of abnormal gene expression associated with vascular complications [14][15]. Group 5: "Counterclockwise" Aging Program - Remarkably, weight loss significantly downregulated various aging markers in multiple cell types, reducing the aging score and the number of p21-positive cells. This "rejuvenation" effect was particularly notable in metabolic, precursor, and vascular cells. Molecular mechanism analysis revealed a conserved transcription factor network in stressed aging cells, which weight loss effectively "shut down," restoring cellular health programs [17][18].