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Cell Metab. 2015 Dec 1;22(6):1045-58. doi: 10.1016/j.cmet.2015.09.013. Epub 2015 Oct 17.

Leptin Deficiency Shifts Mast Cells toward Anti-Inflammatory Actions and Protects Mice from Obesity and Diabetes by Polarizing M2 Macrophages.

Author information

1
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Nephrology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
2
Department of Nephrology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China. Electronic address: yuxq@mail.sysu.edu.cn.
3
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Research Institute of Nephrology, Nanjing University School of Medicine, Nanjing 210002, China.
4
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
5
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Biological Sciences, School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei 230009, China.
6
INSERM, U 872, Paris, F-75006 France, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, UMRS 872, Paris, F-75006 France; Université Paris Descartes, UMRS 872, Paris, F-75006 France.
7
Department of Genetics and Complex Diseases, School of Public Health, Harvard University, Boston, MA 02115, USA.
8
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: gshi@rics.bwh.harvard.edu.

Abstract

Mast 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.

PMID:
26481668
PMCID:
PMC4670585
DOI:
10.1016/j.cmet.2015.09.013
[Indexed for MEDLINE]
Free PMC Article

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