Depletion of CD2M2-Like Macrophages Promotes the Browning of the White Adipose Tissue

We have previously shown that CD2M2-like macrophages constitute a microenvironment for adipocyte progenitors (APs), in a Tgfβ-dependent manner, to retain systemic insulin sensitivity by tuning the quiescence/proliferation balance of APs to adapt to changes in nutritional status. Previously we generated CD206DTR transgenic mice and CD206-CreERT2/ Tgfβ1 flox/flox (Tgfβ1 KO) mice to determine the role of CD2M2-like macrophages a role of CD206+ cell specific Tgfβ1 respectively, in the APs proliferation. Previous reports have shown that M2-like macrophages play a key role in the browning of WAT via activation of type 2 cytokines production during cold exposure. These findings revealed the relationship between the occurrence of beige adipocytes and M2-like macrophage recruitment. In order to investigate the role of CD2M2-like macrophages in the induction of browning into the WAT, we extended our study to see the browning phenomenon by using CD206DTR and Tgfβ1 KO mice. Here, we show that depletion of CD2M2-like macrophages promotes the browning of WAT. We report that cold stimulation resulted in the generation of smaller adipocytes, upregulation of UCP1 and CD137 , a marker for beige progenitors, in the WAT of CD206-ablated mice. Flow cytometry analysis further confirmed enhanced beige progenitors in the WAT. Since blocking of Tgfβ is known to promote browning of the WAT. Mechanistically, we assume that enhanced browning into the WAT of CD206DTR mice might be due to the deletion of Tgfβ1 from CD206-M2-like macrophages. Taken together, we concluded that CD2M2-like macrophages induce the proliferation of beige progenitors in the WAT, which may serve as effective therapeutic tools for the prevention and treatment of obesity. Disclosure A. Nawaz: Research Support; Spouse/Partner; Kobayashi Foundation, Kobayashi Foundation, Kobayashi Foundation. S. Fujisaka: Research Support; Self; Mochida Pharmaceutical Co., Ltd., Eli Lilly and Company, MSD K.K., Toyama First Bank. I. Usui: None. K. Yagi: None. T. Nakagawa: None. T. Kado: None. K. Tobe: Research Support; Self; Bristol-Myers Squibb Company, Takeda Pharmaceutical Company, Teijin Pharma Limited, Japan Diabetes Society, Eli Lilly and Company, MSD K.K., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Pfizer Inc., Astellas Parma Inc, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Novo Nordisk Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Tsumura u0026 Co., Ono Pharmaceutical Co., Ltd., Novartis Pharma K.K., Sumitomo Dainippon Pharma Co. Y. Igarashi: None. K. Okabe: None. K. Saeki: None.