While the existing literature indicates contribution of different vascular cell types (SMC, EC, macrophages) to leptin-induced atherogenesis, more systematic approaches using cell-specific LepR knockouts and lineage tracing strategies in the background of atherosclerotic models (ApoE-/-, LDL-R-/-) are required to elucidate the fundamental molecular mechanisms by which hyperleptinemia drives lesion pathogenesis in obesity and related metabolic complications. This evidence concerns the gene LEPR and obesity due to melanocortin 4 receptor deficiency.