Expression and Localization of Melanocortin‐1 Receptor in Human Adipose Tissues of Severely Obese Patients

Abstract

The melanocortin system is a key regulator in the hypothalamus of energy intake and expenditure. It is frequently linked with obesity and apparently modulates sympathetic outflow to white adipose tissues. The role of the melanocortins within adipose tissues, however, is not entirely clear. This study was aimed at determining the quantitative expression of the five melanocortin receptors (MC1-R to MC5-R) in subcutaneous and omental fat of obese patients and non-obese subjects. Expression of MC1-R to MC5-R, proopiomelanocortin, agouti signaling protein, leptin, leptin receptor, and uncoupling protein-1 was investigated in human fat samples by quantitative reverse transcription-polymerase chain reaction. MC1-R expression was also studied in preadipocytes, adipocytes, and monocytic THP-1 cells and by immunohistochemical localization in adipose tissues. Notable expression was found for MC1-R, whereas no mRNA for MC2-R and MC3-R was detected; MC4-R and MC5-R mRNA was occasionally detectable but at very low levels. MC1-R mRNA in subcutaneous fat was increased in obese patients as compared with controls; omental fat of both groups had slightly higher MC1-R expression than subcutaneous fat and did not differ between patient groups. Immunohistochemical analysis of the MC1-R in adipose tissue sections showed that MC1-R expression was higher in macrophages but also present in adipocytes. The expression of MC1-R and the lack of MC2-R in human adipose tissues indicate that the melanocortins may regulate cell proliferation and/or inflammatory signals rather than lipolysis. Also, the increased expression of MC1-R in subcutaneous fat of obese subjects may reflect one aspect of the pathophysiology of obesity.