PPARγ Activation Rescues High‑Fat Diet‑Induced Obesity Exacerbated Food Allergy by Maintaining Intestinal Homeostasis

High-fat diet (HFD)-induced obesity has been suggested to be a potential risk factor for the increasing incidence of food allergies, yet the underlying mechanisms remain unknown. Here, we investigated the causal role of peroxisome proliferator-activated receptor gamma (PPARγ) in HFD-induced obesity exacerbated food allergy using both in vitro and in vivo approaches. In bone marrow‑derived mast cells (BMMCs), pharmacological inhibition of PPARγ enhanced IgE‑mediated degranulation and IL‑4 secretion without affecting IgE‑FcεRI binding, indicating that PPARγ negatively regulates mast cell activation independently of the initial receptor engagement. In HFD‑fed mice with ovalbumin‑induced food allergy, oral administration of the PPARγ agonist rosiglitazone alleviated allergic reactions by reducing mucosal mast cell activation, without significantly altering IgE levels. Mechanistically, PPARγ activation restored intestinal barrier integrity, expanded RORγt⁺ regulatory T cells in mesenteric lymph nodes, and reversed gut dysbiosis, particularly by restoring Ligilactobacillus abundance. Collectively, these findings establish that PPARγ suppression is a causal mediator of obesity‑exacerbated food allergy and highlight PPARγ as a potential target for preventive strategies against allergic disease in the context of obesogenic dietary patterns.