1. Academic Validation
  2. Bone marrow immune cells respond to fluctuating nutritional stress to constrain weight regain

Bone marrow immune cells respond to fluctuating nutritional stress to constrain weight regain

  • Cell Metab. 2023 Sep 7;S1550-4131(23)00304-2. doi: 10.1016/j.cmet.2023.08.009.
Hai-Yan Zhou 1 Xu Feng 1 Li-Wen Wang 1 Rui Zhou 1 Heng Sun 1 Xin Chen 1 Ren-Bin Lu 1 Yan Huang 1 Qi Guo 1 Xiang-Hang Luo 2
Affiliations

Affiliations

  • 1 Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
  • 2 Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China; Key Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Hunan 410008, China. Electronic address: xianghangluo@csu.edu.cn.
Abstract

Weight regain after weight loss is a major challenge in the treatment of obesity. Immune cells adapt to fluctuating nutritional stress, but their roles in regulating weight regain remain unclear. Here, we identify a stem cell-like CD7+ monocyte subpopulation accumulating in the bone marrow (BM) of mice and humans that experienced dieting-induced weight loss. Adoptive transfer of CD7+ monocytes suppresses weight regain, whereas inducible depletion of CD7+ monocytes accelerates it. These cells, accumulating metabolic memories via epigenetic adaptations, preferentially migrate to the subcutaneous white adipose tissue (WAT), where they secrete fibrinogen-like protein 2 (FGL2) to activate the protein kinase A (PKA) signaling pathway and facilitate beige fat thermogenesis. Nevertheless, CD7+ monocytes gradually enter a quiescent state after weight loss, accompanied by increased susceptibility to weight regain. Notably, administration of FMS-like tyrosine kinase 3 ligand (FLT3L) remarkably rejuvenates CD7+ monocytes, thus ameliorating rapid weight regain. Together, our findings identify a unique bone marrow-derived metabolic-memory immune cell population that could be targeted to combat obesity.

Keywords

CD7+ monocytes; bone marrow; obesity; thermogenesis; weight regain.

Figures
Products
Inhibitors & Agonists