Histological and transcriptomic analyses of lipedema SAT confirm adipocyte hypertrophy, interstitial fibrosis, microvascular alterations and a predominance of CD68+/CD163+ macrophages, together with dysregulation of transcription factors such as CEBPD and KLF4 and of genes involved in adipogenesis, extracellular matrix remodelling and myeloid cell activation (e.g., CSF1R, TREM2, MAFB, C1Q, C2, CD84, CD209), delineating a typical picture of “sick fat” that differs from both simple obesity and lymphedema [56,57]. Here, C2 is linked to obesity due to melanocortin 4 receptor deficiency.