High fat diet promotes asthma by inhibiting the differentiation of regulatory T cells via E3 ubiquitin ligase ITCH

Abstract

Obesity, a rising global health issue, has been linked to the exacerbation of asthma, increasing both the risk of onset and disease severity. High-fat diet (HFD) has been shown to influence immune responses and worsen asthma in murine models, although the exact mechanisms remain unclear. In our study, we found that HFD significantly reduced the population of regulatory T cells (Tregs) in the lungs and led to increased eosinophilic inflammation in asthma. HFD was linked to alterations in lipid metabolism, particularly through the activation of the lipogenic enzyme acetyl-CoA carboxylase (ACC1) and inhibition of fatty acid oxidation. Additionally, treatment with Etomoxir, a CPT-1a inhibitor, diminished Treg proportions and Foxp3 expression. We also revealed that the E3 ubiquitin ligase ITCH, which regulates Treg function, was downregulated at the protein level under HFD conditions, despite unchanged mRNA levels. Overall, our research findings highlight the impact of high-fat diets on Treg function and immune regulation, providing insights for potential therapeutic strategies targeting lipid metabolism in inflammatory diseases like asthma.

Keywords: Asthma; High fat diet; ITCH; Treg.