SOSTDC1 downregulation in CD4⁺ T cells confers protection against obesity-induced insulin resistance.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-04-01 DOI:10.1016/j.celrep.2025.115496

Dehai Li, Jing Zhu, Mingyue Zhang, Qiping Shi, Rong Guo, Daming Zhang, Pei Zheng, Hua Zhang, Guangqiang Li, Jie Wu, Guodong Sun, Qiong Wen, Jingyi Tan, Zonghua Liu, Xindong Liu, Hengwen Yang, Hongyun Lu, Guangchao Cao, Zhinan Yin, Qian Wang

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引用次数: 0

Abstract

Adipose-resident T cells play a crucial role in the development of obesity-induced insulin resistance. However, the specific mechanisms, particularly those involving non-immune cytokines, remain unclear. Here, we report significantly elevated levels of sclerostin domain-containing protein 1 (SOSTDC1) in individuals with type 2 diabetes (T2D), showing positive correlations with fasting glucose and HbA1c. T cell-specific Sostdc1-deficient mice exhibit resistance to age-induced adipose lipid accumulation and glucose dysregulation at 12 months and protect against obesity-induced insulin resistance without affecting proinflammatory macrophage infiltration or adipose inflammation. Mechanistically, SOSTDC1 disrupts the lipid balance in adipocytes by promoting lipogenesis and inhibiting lipolysis through the LRP5/6-β-catenin pathway. Furthermore, T cell receptor (TCR) signaling significantly amplifies SOSTDC1 secretion in CD4⁺ T cells. In summary, our study uncovers an additional mechanism by which T cells contribute to obesity and insulin resistance, suggesting that inhibiting SOSTDC1 could be a promising immunotherapeutic strategy for metabolic disorders.

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.