Melanocortin agonists stimulate lipolysis in human adipose tissue explants but not in adipocytes

Abstract

BackgroundThe central melanocortin system is broadly involved in the regulation of mammalian nutrient utilization. However, the function of melanocortin receptors (MCRs) expressed directly in peripheral metabolic tissues is still unclear. The objective of this study was to investigate the lipolytic capacity of MC1-5R in differentiated adipocytes versus intact white adipose tissue.ResultsNon-selective MCR agonist α-MSH, MC5R-selective agonist PG-901 and MC4R-selective agonist LY2112688 significantly stimulated lipolysis in intact white adipose tissue, whereas stimulation of MCRs in differentiated adipocytes failed to do so. The lipolytic response of MC5R was decreased in intact human white adipose tissue when co-treating with β-adrenergic antagonist propranolol, suggesting that the effect may be dependent on neuronal innervation via noradrenalin release.ConclusionWhen developing an anti-obesity therapeutic drug with selective MC4R/MC5R properties, effects on lipolysis in white adipose tissue may be physiologically relevant.

Melanocortin receptor agonists MCR1‐5 protect photoreceptors from high‐glucose damage and restore antioxidant enzymes in primary retinal cell culture

“…BMS-470539 and PG-901 were used as MCR 1 and MCR 5 agonist, respectively, although PG901 also binds with antagonistic activity MC3R and MC4R [20,21]. Compounds were supplied by Professor Grieco (Pharmacy Department, University of Naples Federico II).…”

The Effect Sizes of PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 Variants on Type 2 Diabetes Mellitus Risk among the Western Saudi Population: A Cross-Sectional Prospective Study

“…The melanocortin 4 receptor (MC4R) gene, located at chromosome 18q21, encodes a G protein-coupled receptor that binds to the α-melanocyte-stimulating hormone. It plays a role in fatty acid metabolism in the liver (promoting lipolysis) and lowering insulin secretion in the pancreas [26]. MC4R is expressed in the hypothalamus in response to the leptin signaling pathways [27,28].…”

“…MC4R is expressed in the hypothalamus in response to the leptin signaling pathways [27,28]. It is believed that MC4R induces lipolysis directly in rabbit adipocytes [29] and at a minimum level in subcutaneous adipocytes of obese humans [30], mediated by the intracellular response to neuronal signals [26]. Association signals were identified between MC4R exonic variants and different levels of obesity.…”

Polymorphisms and mutations in the melanocortin-3 receptor and their relation to human obesity

“…Hypercorticosteronemia is also known to result in increased bone resorption and decreased bone deposition [44], and so the elevated corticosterone could potentially explain decreased linear growth of Mc3r -deficient mouse models. A study from Moller et al demonstrated mRNA expression of MC3R in human subcutaneous adipocytes, albiet to a lesser extent than MC1R, MC2R , or MC5R [23]. Additionally You et al showed mRNA expression of Mc3r in rat brain, liver and adipose tissue [45].…”