Pan Xiao-Xi, Yao Kang-Li, Yang Yong-Feng, Ge Qian, Zhang Run, Gao Ping-Jin, Ruan Cheng-Chao, Wu Fang
Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Cell Dev Biol. 2021 Mar 4;9:637424. doi: 10.3389/fcell.2021.637424. eCollection 2021.
Aging-associated chronic inflammation is a key contributing factor to a cluster of chronic metabolic disorders, such as cardiovascular disease, obesity, and type 2 diabetes. Immune cells particularly T cells accumulate in adipose tissue with advancing age, and there exists a cross talk between T cell and preadipocyte, contributing to age-related adipose tissue remodeling. Here, we compared the difference in morphology and function of adipose tissue between young (3-month-old) and old (18-month-old) mice and showed the phenomenon of brown adipose tissue (BAT) "whitening" in old mice. Flow cytometry analysis suggested an increased proportion of T cells in BAT of old mice comparing with the young and exhibited senescent characteristics. We take advantage of coculture system to demonstrate directly that senescent T cells inhibited brown adipocyte differentiation of preadipocytes in adipose tissue. Mechanistically, both and studies suggested that senescent T cells produced and released a higher level of IFN-γ, which plays a critical role in inhibition of preadipocyte-to-brown adipocyte differentiation. Taken together, the data indicate that senescent T cell-derived IFN-γ is a key regulator in brown adipocyte differentiation.
衰老相关的慢性炎症是导致一系列慢性代谢紊乱的关键因素，如心血管疾病、肥胖症和2型糖尿病。免疫细胞尤其是T细胞会随着年龄的增长在脂肪组织中积累，并且T细胞与前脂肪细胞之间存在相互作用，这导致了与年龄相关的脂肪组织重塑。在此，我们比较了年轻（3个月大）和年老（18个月大）小鼠脂肪组织在形态和功能上的差异，并展示了老年小鼠棕色脂肪组织（BAT）“变白”的现象。流式细胞术分析表明，与年轻小鼠相比，老年小鼠BAT中T细胞的比例增加且呈现衰老特征。我们利用共培养系统直接证明衰老的T细胞会抑制脂肪组织中前脂肪细胞向棕色脂肪细胞的分化。从机制上讲， 和 研究均表明衰老的T细胞产生并释放更高水平的干扰素-γ，这在抑制前脂肪细胞向棕色脂肪细胞分化中起关键作用。综上所述，数据表明衰老T细胞来源的干扰素-γ是棕色脂肪细胞分化的关键调节因子。
