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

Yi Zhou; Xueqing Yu; Huimei Chen; Sara Sjöberg; Joséphine Roux; Lijun Zhang; Al-Habib Ivoulsou; Farid Bensaid; Cong-Lin Liu; Jian Liu; Joan Tordjman; Karine Clement; Chih-Hao Lee; Gokhan S Hotamisligil; Peter Libby; Guo-Ping Shi

doi:10.1016/j.cmet.2015.09.013

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

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

Authors

Yi Zhou¹, Xueqing Yu², Huimei Chen³, Sara Sjöberg⁴, Joséphine Roux⁴, Lijun Zhang⁴, Al-Habib Ivoulsou⁴, Farid Bensaid⁴, Cong-Lin Liu⁴, Jian Liu⁵, Joan Tordjman⁶, Karine Clement⁶, Chih-Hao Lee⁷, Gokhan S Hotamisligil⁷, Peter Libby⁴, Guo-Ping Shi⁸

Affiliations

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.

Publication types

Research Support, N.I.H., Extramural
Comment

MeSH terms

Animals
Diabetes Mellitus
Humans
Leptin / deficiency*
Macrophages
Mast Cells*
Mice
Mice, Inbred C57BL
Mice, Obese
Obesity

Substances

Leptin

Abstract

Publication types

MeSH terms

Substances

Grants and funding