《Nature》权威发布：减肥究竟怎样重构你的脂肪生态系统？

Core Viewpoint - The article discusses a groundbreaking study that reveals the changes in the adipose tissue microenvironment during obesity and weight loss, providing insights for clinical interventions and metabolic health management [18]. Group 1: Overview of Adipose Tissue Remodeling - The study constructed a single-cell atlas of adipose tissue from 70 subjects, analyzing 171,247 cells, including 25 severely obese individuals (pre- and post-surgery) and 24 healthy weight individuals, focusing on subcutaneous abdominal fat [8]. - In obese individuals, there is an abnormal accumulation of immune cells (macrophages, lymphocytes) and a decrease in mature adipocytes, indicating cell apoptosis or insufficient new cell formation; these abnormalities significantly improve after weight loss [8]. Group 2: Abnormal Activation of Macrophages - The proportion of macrophages in adipose tissue increases from 14% to 31% during obesity, particularly lipid-associated macrophages (LAMs), which show enhanced expression of lipid metabolism and inflammation markers [10]. - Weight loss reduces the macrophage proportion to 18% and decreases the expression of inflammation-related genes, although some metabolic activation may not fully reverse, suggesting an epigenetic "memory" [10]. Group 3: Newborn Adipocytes and Metabolic Adaptation - Eight types of mature adipocytes were identified, with "stress-type" (AD3) and "fibrotic-type" (AD6) significantly increasing in obesity, while "lipid-synthesis-type" (AD5) decreases; weight loss effectively reduces the stress-type cells and restores the lipid-synthesis-type [12]. - Obese adipocytes show insufficient fatty acid and branched-chain amino acid (BCAA) breakdown, while weight loss enhances adipocyte metabolic flux, promoting lipid cycling and BCAA breakdown, which improves insulin sensitivity [12]. Group 4: Reversal of Multi-Cellular "Stress" State - Adipose precursor cells (APCs) identify multiple subtypes, with the "stress-type" (APC3) increasing in obesity; weight loss reduces the proportion of stress-type and fibrotic APCs and downregulates hypoxia and anti-adipogenic signals [14]. - In vascular cells, capillary endothelial and wall cells exhibit "stress-type" subpopulations, expressing genes related to vascular disease and fibrosis, which are effectively reduced after weight loss [14]. Group 5: Weight Loss Delays Cellular Aging - Weight loss downregulates multiple cellular aging markers (e.g., CDKN1A/p21), reducing the aging characteristics of adipose, precursor, and vascular cells [16]. - Transcriptional regulation shows that stress and aging cells share a common network that drives cell cycle arrest and inflammation signaling, which can be effectively shut down or alleviated by weight loss [16].