同一靶点双重机制！《自然·代谢》揭开GIPR‘激活抑制’均能减重奇迹

Core Insights - A groundbreaking study published in the journal Nature reveals the biological mechanism behind why individuals regain weight after losing it, highlighting the phenomenon of "inflammatory memory" in fat cells [5][7]. Group 1: Research Findings - The research, led by a team from ETH Zurich, discovered that even after successful weight loss, human fat cells retain an epigenetic "memory" of their previous obese state, which contributes to weight regain [7]. - Using high-precision single-cell RNA sequencing (snRNA-seq), the study compared fat tissue samples from humans and mouse models, finding significant transcriptional changes in fat tissue post-weight loss [7]. - Notably, the "pro-inflammatory memory" in macrophages is particularly persistent, remaining even after weight normalization, indicating a lasting inflammatory signal [7]. Group 2: Implications for Weight Management - The study suggests that the longer an individual has been obese, the stronger the impact of this "fat memory," which may explain why long-term obese individuals find it harder to maintain weight loss [7]. - While weight loss can eliminate some senescent cells and reverse immune dysregulation, it does not fully eradicate the pro-inflammatory memory in macrophages, indicating that future weight loss therapies may need to target this inflammatory memory mechanism for effective long-term weight management [7]. - This scientific breakthrough could shift the understanding of obesity treatment from simple weight loss to more complex strategies aimed at "resetting cellular memory," offering new hope for billions affected by obesity globally [7].