Zhou, YiYu, XueqingChen, HuimeiSjöberg, SaraRoux, JoséphineZhang, LijunIvoulsou, Al-HabibBensaid, FaridLiu, JianTordjman, JoanClement, KarineLee, Chih-HaoLibby, PeterShi, Guo-PingHotamisligil, GokhanLiu, Conglin2018-12-192015-12Zhou, Yi, Xueqing Yu, Huimei Chen, Sara Sjöberg, Joséphine Roux, Lijun Zhang, Al-Habib Ivoulsou, et al. 2015. “Leptin Deficiency Shifts Mast Cells toward Anti-Inflammatory Actions and Protects Mice from Obesity and Diabetes by Polarizing M2 Macrophages.” Cell Metabolism 22 (6): 1045–58. https://doi.org/10.1016/j.cmet.2015.09.013.1550-4131http://nrs.harvard.edu/urn-3:HUL.InstRepos:37939884Mast cells (MCs) contribute to the pathogenesis of obesity and diabetes. This study demonstrates that leptin deficiency slants MCs toward anti-inflammatory functions. MCs in the white adipose tissue (WAT) of lean humans and mice express negligible leptin. Adoptive transfer of leptin-deficient MCs expanded ex vivo mitigates diet-induced and pre-established obesity and diabetes in mice. Mechanistic studies show that leptin-deficient MCs polarize macrophages from M1 to M2 functions because of impaired cell signaling and an altered balance between pro-and anti-inflammatory cytokines, but do not affect T cell differentiation. Rampant body weight gain in ob/ob mice, a strain that lacks leptin, associates with reduced MC content in WAT. In ob/ob mice, genetic depletion of MCs exacerbates obesity and diabetes, and repopulation of ex vivo expanded ob/ob MCs ameliorates these diseases.en-USCell BiologyPhysiologyMolecular BiologyJournal Article2018-12-1910.1016/j.cmet.2015.09.013