High fat diets rich in fish oil promote hair loss via epidermal fatty acid binding-mediated immunoregulation

While fats are essential nutrients in healthy diets, how dietary fats affect immune cell function and overall health are not well understood. We fed mice various high-fat diets (HFD) which mimicked human diets rich in different fatty acid (FA) components. Surprisingly, we observed that mice consuming the fish oil diet exhibited the most severe hair loss compared to those consuming other diets, which supported the evidence that people in regions with a high intake of fish had a tendency of increased hair loss. Mechanistically, omega-3 FAs in fish oil promoted atypical expansion of skin CD8+γδ+ T cells which inhibited hair follicle stem cell activity. We further identified that the epidermal fatty acid binding protein (E-FABP) was pivotal in promoting omega-3 FA-induced CD8+γδ+ T cells by activating the reactive oxygen species (ROS)/IL-36 signaling pathway in dermis macrophages. Our findings have implications for the prevention, etiology and therapy of hair loss in humans, including these with alopecia areata. Transcriptional profile of mice on low fat diet (LFD), fish oil diet, or cocoa butter diet for both wild type (WT) and epidermal fatty acid binding protein (E-FABP) knockout mice with n=3 in each group.