Deficiency of heat shock protein A12A promotes browning of white adipose tissues in mice.

Browning of white adipose tissues (WAT) is critical for a variety of physiological and pathophysiological events. Given the limited understanding in molecular control of WAT browning, further research is needed. Heat shock protein A12A is a new member of multigene Hsp70 family. This study investigated the effect of on the browning of WAT. WAT Browning in mice was induced by cold exposure for 5 days. We observed that nuclear Hduanyu184212A content was increased in WAT after cold exposure, while deficiency of Hduanyu184212A (Hspa12a^-/-) promoted the cold-induced browning of WAT in mice compared to wild type (WT) littermates. Accordingly, Hspa12a^-/- mice showed attenuation of body temperature drop and increase of thermogenic gene expression compared to WT mice after cold exposure. However, in vitro experiments demonstrated that Hduanyu184212A deficiency in primary white adipocytes did not affect their browning and thermogenic gene expression. Further loss- and functional studies revealed that Hduanyu184212A deficiency promoted whereas Hduanyu184212A overexpression impeded M2 macrophage polarization. Importantly, the conditioned medium (CM) from Hspa12a^-/- bone marrow-derived macrophages (BMDMs) enhanced the browning of primary white adipocytes when compared to the CM from WT BMDMs. The data identified macrophage Hduanyu184212A as a novel regulator of WAT browning through a paracrine mechanism. Targeting Hduanyu184212A might provide meaningful advances for the management of browning-associated physiological events such as hypothermia adaptation and pathophysiological disorders such as obesity and cancer-related cachexia.

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