减重药物界最大谜团破解！同一受体"激活"或"抑制"都能减肥？《自然·代谢》揭秘GIPR双重作用机制的生命科学革命

Core Insights - A groundbreaking study published in the journal Nature reveals the biological mechanisms 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 the ETH Zurich team 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 remains persistent, indicating that inflammatory signals continue to exist even when body weight normalizes [7]. Group 2: Implications for Weight Management - The study indicates that the longer an individual has been obese, the stronger the impact of this "fat memory," explaining why long-term obese individuals are more prone to weight regain after dieting [7]. - While weight loss can eliminate some senescent cells and reverse immune dysregulation, it does not fully eradicate the pro-inflammatory memory in macrophages, suggesting 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 a simple "weight loss" approach to a more complex "cellular memory reset" strategy, offering new hope for billions affected by obesity globally [7].