The Paradox of Ectopic Melanin Synthesis in Adipose: Potential Mechanism, Benefits and Perspectives in Abating Obesity Complications

Obesity and related non-communicable diseases (NCDs) are global health challenges prevalent worldwide. Intervention became imperative for creative natural measures to minimize NCDs. The chronic state of inflammation and oxidative stress are the land mark signatures for obesity driven NCDs. In this description study, we try to decipher and rationalize the new puzzle of ectopic melanin synthesis in adipose by formulating analytical view from extensive literature review. Oxidative stressed adipose triggers structural homeostasis program to initiate renovation of adipose tissue for self-healing. These processes are induced by rewiring interactions of signalling pathways for promoting adipocytes survival or replenishing them from their precursors. We postulate that melanogenesis and adipogenesis are co-driven by sharing interactive molecular signalling mechanisms. Cross-talk between melanogenesis and adipogenesis occurs through Wnt/β-catenin pathway and its interaction with Sox signalling molecules; through PPAR-γ and C/EBP-α. Activating these signalling pathways stimulate adipogenesis to relief the oxidative stress induced cell damages. Ectopic melanin synthesis and adipogenesis concurrently occur as adaptative response to hypertrophic induced oxidative stress and ROS as second messengers. Therefore, the activation of melanin synthesis probably is a natural preventive measure to slow down or minimizes hyperplasia and ameliorates consequent obesity complications. In conclusion; before we recommend using analogs of melanin inducers as therapeutic strategy, we advocate the use of the melanin intermediates as antioxidants or antiinflammatory agents in obesity research and therapy. This descriptive study is based on very limited amount of preliminary data and at times several levels of assumptions are made. The hypothesis of melanin production in adipose tissue having a role to prevent complications of obesity is unconventional and challenges current dogma.