RETN and Insulin resistance: In addition to leptin dysregulation, several other contributors—including insulin resistance, mitochondrial dysfunction, oxidative stress, proinflammatory adipokines such as MCP-1 and resistin, and gut microbiota-derived endotoxins—are implicated in driving peripheral and central inflammation (Deopurkar et al., 2010; Guillemot-Legris and Muccioli, 2017).