《Nature》重磅发布：脂肪的“记忆”与“遗忘”：新研究揭秘减重如何逆转衰老的细胞机制

Core Insights - The article emphasizes the importance of understanding obesity through advanced scientific techniques, particularly single-nucleus RNA sequencing and spatial transcriptomics, which provide a detailed view of cellular changes in adipose tissue [6][7][12] Group 1: Research Findings - The study included three groups: 24 healthy individuals, and 25 obese individuals before and after weight loss surgery, revealing that weight loss surgery reduced the average BMI from 45.2 to 35.2, significantly improving fasting insulin and insulin resistance [7] - Analysis of over 170,000 cells identified more than 20 different cell states, showing a clear distinction in cellular organization between healthy and obese individuals, with a notable increase in macrophages in obese tissue [7][8] - In obese individuals, macrophages constituted 31% of adipose tissue, compared to 14% in healthy individuals, indicating a shift in immune cell dynamics [8] Group 2: Cellular Dynamics - The study identified two subtypes of lipid-associated macrophages (LAMs) in obese tissue: adaptive LAMs, which efficiently process lipids, and inflammatory LAMs, which are associated with insulin resistance [8][9] - The proportion of "stress-type" adipocytes in obese tissue was found to be 55%, which dropped to 14% post-weight loss, indicating a significant reduction in unhealthy adipocyte types [9][10] - The research linked obesity to cellular senescence, revealing that "stress-type" adipocytes express high levels of the senescence marker p21, which were largely eliminated after weight loss [10] Group 3: Implications for Treatment - The findings suggest that weight loss is not only about reducing fat but also involves a systemic cleansing of senescent cells, enhancing overall tissue health [12] - The persistence of inflammatory macrophages post-weight loss raises concerns about potential metabolic rebound, highlighting the need for preventive strategies [12] - The research provides insights into potential future treatments for obesity, focusing on targeting dysfunctional cells and signaling pathways rather than solely addressing energy balance [12]