CD301b+ Mononuclear Phagocytes Maintain Positive Energy Balance through Secretion of Resistin-like Molecule Alpha

• Published in: Immunity (Cambridge, Mass.) Mass.), 2016-09, Vol.45 (3), p.583-596
• Main Authors: Kumamoto, Yosuke, Camporez, Joao Paulo G., Jurczak, Michael J., Shanabrough, Marya, Horvath, Tamas, Shulman, Gerald I., Iwasaki, Akiko
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; adipose tissue macrophage; alternatively activated macrophage; Animals; Cytokines; Energy Metabolism - physiology; Female; Genes; Genotype & phenotype; Glucose; glucose metabolism; Homeostasis; Insulin; Insulin - metabolism; Insulin resistance; Insulin Resistance - physiology; Intercellular Signaling Peptides and Proteins - metabolism; Lectins, C-Type - metabolism; Macrophages - metabolism; Male; Metabolic disorders; Metabolites; Mice; Mice, Inbred C57BL; Obesity; Phagocytes - metabolism; Proteins; Rodents
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2016.08.002

Mononuclear phagocytes (MNPs) are a highly heterogeneous group of cells that play important roles in maintaining the body’s homeostasis. Here, we found CD301b (also known as MGL2), a lectin commonly used as a marker for alternatively activated macrophages, was selectively expressed by a subset of CD11b+CD11c+MHCII+ MNPs in multiple organs including adipose tissues. Depleting CD301b+ MNPs in vivo led to a significant weight loss with increased insulin sensitivity and a marked reduction in serum Resistin-like molecule (RELM) α, a multifunctional cytokine produced by MNPs. Reconstituting RELMα in CD301b+ MNP-depleted animals restored body weight and normoglycemia. Thus, CD301b+ MNPs play crucial roles in maintaining glucose metabolism and net energy balance. [Display omitted] •In vivo depletion of CD301b+ MNPs results in reduced food intake and weight loss•Depletion of CD301b+ MNPs reduces blood glucose and increases insulin sensitivity•CD301b+ MNP-depleted mice have decreased serum RELMα concentration•Reconstitution of RELMα restores body weight and normoglycemia Mononuclear phagocytes play an integral role in the regulation of whole-body metabolism. Kumamoto et al. demonstrated that CD301b+ mononuclear phagocytes in adipose tissues secrete resistin-like molecule alpha (RELM-α) to maintain positive energy balance.