Characterization of murine melanocortin receptors mediating adipocyte lipolysis and examination of signalling pathways involved

Cathrine Laustrup Møller, Kirsten Raun, Marianne Lambert Jacobsen, Thomas Åskov Pedersen, Birgitte Holst, Kilian W Conde-Frieboes, Birgitte Schjellerup Wulff

    28 Citations (Scopus)

    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.

    Original languageEnglish
    JournalMolecular and Cellular Endocrinology
    Volume341
    Issue number1-2
    Pages (from-to)9-17
    Number of pages9
    ISSN0303-7207
    DOIs
    Publication statusPublished - 20 Jul 2011

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