以下文章来源于肥胖世界ObesityWorld ，作者肥胖世界 肥胖世界ObesityWorld . 《肥胖世界》Obesity World - 同步传真肥胖及代谢国际新学术进展，为医学减重临床、教研人员搭建一座与国际接轨的桥梁，「每医健」旗下内容平台。 全球已有超10亿人被肥胖困扰。许多人以为"胖"仅是外表问题，殊不知腹部脂肪的异常实际上是代谢疾病的"隐形杀手"——它悄然引发胰岛素 抵抗、糖尿病、心血管疾病，甚至提高癌症风险。令人惊奇的是，减重能迅速扭转这些健康危机：血糖平稳了、血压下降了、血管恢复弹性 了。但科学界一直未能破解这一谜团：脂肪组织内部到底经历了什么变化？是细胞数量减少了？还是基因表达重新"洗牌"了？ 为揭开这一谜团，伦敦帝国理工学院的Tricia Tan和William R. Scott领导的研究团队运用单细胞核测序技术分析了70人超过17万个脂肪细胞， 并结合前沿空间转录组学，首次绘制了肥胖状态下脂肪组织的"病变地图"，以及减重如何让它实现"凤凰涅槃"。 一、脂肪组织重塑全景图 研究团队构建了迄今最全面的脂肪组织单细胞图谱，涵盖171,247个细胞，样本来自25名极度肥胖者（术前及减重后） ...

Core Insights - The article discusses the global obesity crisis, highlighting that over 1 billion people are affected by obesity, which is linked to various metabolic diseases and health risks [6][8]. - It emphasizes the importance of understanding the changes in adipose tissue during weight loss, revealing new insights into the mechanisms behind obesity and potential therapeutic approaches [18]. Group 1: Adipose Tissue Remodeling - A comprehensive single-cell atlas of adipose tissue was created, analyzing over 171,000 cells from 25 severely obese individuals and 24 healthy individuals, focusing on subcutaneous abdominal fat [8]. - The study found an influx of immune cells, particularly macrophages and lymphocytes, in obese adipose tissue, while the proportion of mature adipocytes decreased, indicating cell death or insufficient renewal [8][10]. - Weight loss effectively alleviated these pathological changes in adipose tissue [8]. Group 2: Macrophage Memory Effect - The proportion of macrophages in adipose tissue increased from 14% to 31% in obesity, with lipid-associated macrophages (LAMs) being predominant [10]. - Metabolic analysis showed that obese macrophages exhibited a globally hypermetabolic state, activating various metabolic pathways [10]. - After weight loss, macrophage numbers significantly decreased to 18%, and inflammatory gene expression was downregulated, but the hypermetabolic state did not fully reverse, suggesting an "epigenetic memory" [10]. Group 3: Fat Cell Metabolism Reboot - Eight subtypes of mature adipocytes were identified, with stress and fibrotic types increasing in obesity, while lipid synthesis types decreased [12]. - Weight loss led to a significant reduction in stress-type adipocytes and a restoration of lipid synthesis-type cells [12]. - Enhanced metabolic flux in adipocytes post-weight loss was linked to improved insulin sensitivity [12]. Group 4: Decline of Stress Ecological Niche - The study identified an increase in stress-type adipose precursor cells (APCs) in obese individuals, which were associated with hypoxia [14]. - Weight loss significantly reduced the proportion of stress-type and fibrotic APCs, downregulating hypoxia and anti-adipogenic signals [14]. - The vascular system also showed stress-type subpopulations, which were reduced after weight loss [14]. Group 5: Reversal of Aging Programs - Remarkably, weight loss significantly downregulated various senescence markers across multiple cell types, reducing the aging score and the number of p21-positive cells [17]. - The study revealed a conserved transcription factor network in senescent cells that drives a vicious cycle of cell cycle arrest and senescence-associated secretory phenotype (SASP) [17]. - Weight loss effectively "shut down" this network, rebooting cellular health programs [17].