Partial depletion of CD206-positive M2-like macrophages induces proliferation of beige progenitors and enhances browning after cold stimulation

Beige adipocytes are an inducible form of thermogenic adipocytes that become interspersed within white adipose tissue (WAT) depots in response to cold exposure. Previous studies have shown that type 2 cytokines and M2 macrophages induce cold-induced browning in inguinal WAT (ingWAT) by producing catecholamines. Exactly how the conditional and partial depletion of CD206⁺ M2-like macrophages regulates the cold-induced browning of ingWAT, however, remains unknown. We examined the role of CD206⁺ M2-like macrophages in the cold-induced browning of WAT using genetically engineered CD206DTR mice, in which CD206⁺ M2-like macrophages were conditionally depleted. The partial depletion of CD206⁺ M2-like enhanced UCP1 expression in ingWAT, as shown by immunostaining, and also upregulated the expression of Ucp1 and other browning-related marker genes in ingWAT after cold exposure. A flow cytometry analysis showed that the partial depletion of CD206⁺ M2-like macrophages caused an increase in the number of beige progenitors in ingWAT in response to cold. Thus, we concluded that CD206⁺ M2-like macrophages inhibit the proliferation of beige progenitors and that the partial depletion of CD206⁺ M2-like macrophages releases this inhibition, thereby enhancing browning and insulin sensitivity.