2026-P: Myeloid Sirtuin 6 Is a Molecular Switch of White Adipose Tissue Browning

Abstract

Emerging evidence reveals that cold exposure enhances alternative activation of macrophages. We recently reported that myeloid sirtuin 6 (Sirt6) drives macrophage phenotypes into M2 type. However, its role in adaptive thermogenesis has not been explored. In this study, we demonstrate that myeloid Sirt6 ablation attenuates thermogenic responses in subcutaneous adipose tissue (scWAT) during cold exposure. Compared with wild type mice, myeloid Sirt6 KO (mS6KO) mice displayed a lower core body temperature and were glucose intolerant in response to cold exposure. Accordingly, expression levels of thermogenic proteins and number of multilocular lipid droplets were decreased in scWAT of mS6KO mice. Mechanistically, the infiltration of M2 macrophages in scWAT was impaired in mS6KO mice, which contributed to the suppression of lipolysis in adipocytes. Together, these results establish myeloid Sirt6 as a critical determinant of beige cell formation in scWAT. Disclosure Y. Lee: None.