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p38α Deficiency in T Cells Ameliorates Diet-Induced Obesity, Insulin Resistance and Adipose Tissue Senescence

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posted on 29.03.2022, 19:24 by Deyun Meng, Baohua Zhang, Yanyan Wang, Tingting Zheng, Ran Hu, Bin Wang, Kinya Otsu, Ying Wang, Gonghua Huang
Adipose tissue-resident T cells play vital roles in regulating inflammation and metabolism in obesity, but the underlying mechanisms remain unclear. Here, we showed that high-fat diet (HFD) feeding enhances p38 activity in adipose-resident T cells. T cell-specific deletion of p38a, an essential subunit of p38 expressed in most of immune cells, protected mice from HFD-induced obesity, hepatic steatosis, adipose tissue inflammation and insulin resistance. Mice with p38a deletion in T cells exhibited higher energy expenditure. Mechanistically, p38a promoted T cell glycolysis through mTOR signaling, leading to enhanced Th1 differentiation. Accordingly, genetic deletion of p38a alleviated the ongoing diet-induced obesity. Unexpectedly, p38a signaling in T cells promoted adipose tissue senescence during obesity and aging. Taken together, our results identify p38a in T cells as an essential regulator of obesity, insulin resistance and adipose tissue senescence, and p38a may be a therapeutic target for obese- or aging-associated diseases.

Funding

This work was supported by the National Natural Science Foundation of China (31670897, 91642104, and 81471528 to G.H., and 82001702 to T.Z.), the National Key R&D Program of China (2018YFC0115900 to G.H.) and the British Heart Foundation (CH/11/3/29051 to K.O.).

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