TY - JOUR TI - DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production AU - Zhou, Haiyan AU - Peng, Xinyi AU - Hu, Jie AU - Wang, Liwen AU - Luo, Hairong AU - Zhang, Junyan AU - Zhang, Yacheng AU - Li, Guobao AU - Ji, Yujiao AU - Zhang, Jingjing AU - Bai, Juli AU - Liu, Meilian AU - Zhou, Zhiguang AU - Liu, Feng T2 - Nature Communications AB - Adipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases. DA - 2021/01/12/ PY - 2021 DO - 10.1038/s41467-020-20665-4 DP - www.nature.com VL - 12 IS - 1 SP - 326 LA - en SN - 2041-1723 UR - https://www.nature.com/articles/s41467-020-20665-4 Y2 - 2021/01/13/00:52:06 ER -