瑞士苏黎世联邦理工学院Ferdinand von Meyenn小组发现，脂肪组织在减重后保留肥胖的表观遗传记忆。2024年11月18日，国际知名学术期刊《自然》在线发表了这一成果。

通过使用单核RNA测序，研究人员发现人类和小鼠的脂肪组织在显著减重后仍然保留细胞转录变化。此外，研究人员发现小鼠脂肪细胞的表观基因组在肥胖引起的改变持续存在，这些改变负面影响其功能和对代谢刺激的反应。携带这种肥胖记忆的小鼠表现出加速的反弹性体重增加，且表观遗传记忆能够解释脂肪细胞在进一步高脂饮食下对转录的失调反应。

总之，这些研究结果表明，小鼠脂肪细胞以及可能是其他细胞类型中存在一种肥胖记忆，这种记忆主要基于稳定的表观遗传变化。这些变化似乎使细胞在肥胖环境中为病理性反应做准备，从而导致常见的“溜溜球”效应。未来针对这些变化的治疗可能会改善长期的体重管理和健康结局。

据介绍，减少体重以改善代谢健康和相关并发症是治疗肥胖的主要目标。然而，保持减重是一个相当大的挑战，特别是由于身体似乎保留着一种肥胖记忆，抵抗体重变化。克服这一障碍以实现长期治疗成功非常困难，因为支撑这一现象的分子机制仍然很大程度上未知。

附：英文原文

Title: Adipose tissue retains an epigenetic memory of obesity after weight loss

Author: Hinte, Laura C., Castellano-Castillo, Daniel, Ghosh, Adhideb, Melrose, Kate, Gasser, Emanuel, No, Falko, Massier, Lucas, Dong, Hua, Sun, Wenfei, Hoffmann, Anne, Wolfrum, Christian, Rydn, Mikael, Mejhert, Niklas, Blher, Matthias, von Meyenn, Ferdinand

Issue&Volume: 2024-11-18

Abstract: Reducing body weight to improve metabolic health and related comorbidities is a primary goal in treating obesity1,2. However, maintaining weight loss is a considerable challenge, especially as the body seems to retain an obesogenic memory that defends against body weight changes3,4. Overcoming this barrier for long-term treatment success is difficult because the molecular mechanisms underpinning this phenomenon remain largely unknown. Here, by using single-nucleus RNA sequencing, we show that both human and mouse adipose tissues retain cellular transcriptional changes after appreciable weight loss. Furthermore, we find persistent obesity-induced alterations in the epigenome of mouse adipocytes that negatively affect their function and response to metabolic stimuli. Mice carrying this obesogenic memory show accelerated rebound weight gain, and the epigenetic memory can explain future transcriptional deregulation in adipocytes in response to further high-fat diet feeding. In summary, our findings indicate the existence of an obesogenic memory, largely on the basis of stable epigenetic changes, in mouse adipocytes and probably other cell types. These changes seem to prime cells for pathological responses in an obesogenic environment, contributing to the problematic ‘yo-yo’ effect often seen with dieting. Targeting these changes in the future could improve long-term weight management and health outcomes.

DOI: 10.1038/s41586-024-08165-7

Source: https://www.nature.com/articles/s41586-024-08165-7