[PDF][PDF] Leptin deficiency shifts mast cells toward anti-inflammatory actions and protects mice from obesity and diabetes by polarizing M2 macrophages
Y Zhou, X Yu, H Chen, S Sjöberg, J Roux, L Zhang… - Cell metabolism, 2015 - cell.com
Cell metabolism, 2015•cell.com
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 …
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 …
Summary
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.
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