We demonstrated that, within a short period (8 weeks), an HFD (60% of daily intake) leads to significant changes in metabolism and triggers the development of MetS, with impacts on allodynia and motor activity, as well as changes in the BBB, GFAP, and CX43 intensity and ultrastructural modifications in key brain regions, including the hippocampus, cerebellum, and hypothalamus. Here, GJA1 is linked to metabolic syndrome.