Diet shapes the balance between health and disease, and the detrimental consequences of prolonged high-fat diet (HFD) consumption, including obesity, metabolic dysfunction and chronic inflammation, are well established. However, how HFD affects the immune system at an early stage, and how these initial changes influence the host, remains poorly understood, particularly from the perspective of CD4⁺ T cells. Here, we profiled CD4⁺ T cells across multiple organs of mice fed a normal diet or HFD for 5 weeks. t-SNE analysis of flow cytometry data revealed that intestinal CD4⁺ T cells underwent the most pronounced remodeling among the tissues examined, with a marked reduction in RORγt⁺ Foxp3⁺ regulatory T (Treg) cells. Bulk RNA sequencing of intestinal tissue further uncovered extensive changes in transcriptomic signatures associated with immune cell infiltration, inflammation and tissue regeneration. To connect these tissue-level changes with RORγt⁺ Treg cells, we integrated the HFD-induced intestinal transcriptome with a RORγt⁺ Treg cell gene signature using NicheNet analysis and identified a set of putative ligand–receptor networks. These results provide indirect evidence that, from an early phase of HFD feeding, RORγt⁺ Treg cells communicate with intestinal tissue cells through ligand–receptor interactions, which may initiate early changes in the gut.