Research Article

Cellular & Molecular Immunology advance online publication 19 June 2017; doi: 10.1038/cmi.2017.36

CD4+ T cells memorize obesity and promote weight regain
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Jianghuan Zou1, Beibei Lai1, Mingzhu Zheng2, Qin Chen1, Shujun Jiang1, Anying Song1, Zan Huang1, Peiliang Shi1, Xin Tu1, Di Wang2, Linrong Lu2, Zhaoyu Lin1 and Xiang Gao1

  1. 1State 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, Nanjing, Jiangsu 210061, China
  2. 2Institute of Immunology, Program in Molecular and Cellular Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China

Correspondence: X Gao, Ph.D, and Z Lin, Ph.D, 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, Nanjing, Jiangsu 210061, China. E-mail: gaoxiang@nju.edu.cn or linzy@nju.edu.cn

Received 15 March 2017; Revised 20 April 2017; Accepted 20 April 2017
Advance online publication 19 June 2017

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Abstract

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.

Keywords:

CD4+ T cell; immunodeficiency; metabolism; obesity memory; weight regain