Thermogenic Adipocytes Promote M2 Macrophage Polarization through CNNM4-Mediated Mg Secretion.

ABSTRACT: M2 macrophages promote adipose tissue thermogenesis which dissipates energy in the form of heat to combat obesity. However, the regulation of M2 macrophages by thermogenic adipocytes is unclear. Here, it is identified magnesium (Mg) as a thermogenic adipocyte-secreted factor to promote M2 macrophage polarization. Mg transporter Cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4) induced by ADRB3-PKA-CREB signaling in thermogenic adipocytes during cold exposure mediates Mg efflux and Mg in turn binds to the DFG motif in mTOR to facilitate mTORC2 activation and M2 polarization in macrophages. In obesity, downregulation of CNNM4 expression inhibits Mg secretion from thermogenic adipocytes, which leads to decreased M2 macrophage polarization and thermogenesis. As a result,

SUBMITTER: Zhang A 

PROVIDER: S-EPMC11653670 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature