The increased incidence of malignant melanoma in obese individuals is due to impaired melanogenesis and melanocyte DNA repair

Abstract

Obese individuals have a higher incidence of malignant melanoma (MM). We here suggest that the higher incidence is caused by a reduction of melanogenesis and a decreased capacity of melanocytes DNA repair. These effects are caused by an increase in the haematic levels of melanocyte stimulating hormone (MSH) antagonists, namely of the protein attractin, the melanocyte concentrating hormone (MCH), the agouti related protein (ASRP) and perhaps also agouti protein (ASIP), determining a lower activity of circulating MSH and of melanocortotropin receptors (MCRs) 1 and 4. MCR1 is fundamental in melanocyte DNA repair and melanogenesis, and a reduction of its activity could well account for the increased incidence of MM. All these changes are ultimately caused by the leptin resistance normally present on obese individuals, that is a low effectiveness of leptin in spite of its high circulating level.