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

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.