title: Characterization of murine melanocortin receptors mediating adipocyte lipolysis and examination of signalling pathways involved.
abstract: The melanocortin receptors (MCRs) belong to the G-protein coupled receptors (family A). So far, 5 different subtypes have been described (MC1R-MC5R) and of these MC2R and MC5R have been proposed to act directly in adipocytes and regulate lipolysis in rodents. Using ACTH and α-melanocyte stimulating hormone (α-MSH) generated from proopiomelanocortin (POMC), as well as synthetic MSH analogues to stimulate lipolysis in murine 3T3-L1 adipocytes it is shown that MC2R and MC5R are lipolytic mediators in differentiated 3T3-L1 adipocytes. Involvement of cAMP, phosphorylated extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (PKB), adenosine 5' monophosphate activated protein kinase (AMPK) and Jun-amino-terminal kinase (JNK) in MCR mediated lipolysis were studied. Interestingly, results obtained in 3T3-L1 cells suggest that lipolysis stimulated by α-MSH, NDP-α-MSH, MT-II, SHU9119 and PG-901 is mediated through MC5R in a cAMP independent manner. Finally, we identify essential differences in MCR mediated lipolysis when using 3T3-L1 cells compared to primary adipocytes.
authors: Diabetes Biology and Pharmacology, Novo Nordisk A/S, Novo Nordisk Park, 2760 Maaloev, Denmark. ACML@novonordisk.com
authors: Cathrine Laustrup
authors: CL
authors: Møller
authors: Kirsten
authors: K
authors: Raun
authors: Marianne Lambert
authors: ML
authors: Jacobsen
authors: Thomas Åskov
authors: TÅ
authors: Pedersen
authors: Birgitte
authors: B
authors: Holst
authors: Kilian W
authors: KW
authors: Conde-Frieboes
authors: Birgitte Schjellerup
authors: BS
authors: Wulff