State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, 12 Xuefu Road, Pukou District, 210061, Nanjing, China, Jiangsu.
Institute of Immunology, Program in Molecular and Cellular Biology, Zhejiang University School of Medicine, 310058, Hangzhou, China, Zhejiang.
Cell Mol Immunol. 2018 Jun;15(6):630-639. doi: 10.1038/cmi.2017.36. Epub 2017 Jun 19.
Body weight regain often causes failure of obesity therapies while the underlying mechanism remains largely unknown. In this study, we report that immune cells, especially CD4+ T cells, mediate the 'memory' of previous obese status. In a weight gain-loss-regain model, we found that C57BL/6J mice with an obesity history showed a much faster rate of body weight regain. This obesity memory could last for at least 2 months after previously obese mice were kept at the same body weight as non-obese mice. Surprisingly, such obesity memory was abrogated by dexamethasone treatment, whereas immunodeficient Rag1 and H2A mice failed to establish such memory. Rag1 mice repossessed the obesity memory when immune cells or CD4+ T cells isolated from previously obese mice were transferred. Furthermore, depletion of CD4+ T cells led to obesity memory ablation. Taken together, we conclude that CD4+ T cells mediate obesity memory and promote weight regain.
体重反弹常常导致肥胖症治疗失败，但其潜在机制仍不清楚。在这项研究中，我们报告称免疫细胞，特别是 CD4+T 细胞，介导了先前肥胖状态的“记忆”。在体重增加-减少-再增加模型中，我们发现具有肥胖史的 C57BL/6J 小鼠体重恢复速度要快得多。这种肥胖记忆至少可以持续 2 个月，即使先前肥胖的小鼠与非肥胖小鼠保持相同的体重。令人惊讶的是，地塞米松治疗可以消除这种肥胖记忆，而免疫缺陷 Rag1 和 H2A 小鼠则无法建立这种记忆。当将先前肥胖小鼠的免疫细胞或 CD4+T 细胞转移到 Rag1 小鼠中时，它们重新获得了肥胖记忆。此外，耗尽 CD4+T 细胞会导致肥胖记忆消失。综上所述，我们得出结论，CD4+T 细胞介导肥胖记忆并促进体重反弹。
