Characterization of Murine Melanocortin Receptors Mediating Adipocyte Lipolysis and Examination of Signalling Pathways Involved

Cathrine Laustrup Møller (1) , Kirsten Raun , Marianne Lambert Jacobsen , Thomas Åskov Pedersen , Birgitte Holst (1) , Kilian W. Conde-Frieboes , Birgitte Schjellerup Wulff

1 Department of Neuroscience and Pharmacology (Blegdamsvej 3B

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 a-melanocyte stimulating hormone (a-MSH) generated from proopiomelanocortin (POMC), as well as synthetic MSHanalogues 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' monophosphateactivated 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 a-MSH, NDPa- 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.

Mots clés: Melanocortin receptor 1-5; lipolysis; NEFA; adipocytes; real time PCR; Western blotting; signalling; cAMP; extracellular signal-regulated kinase (ERK); protein kinase B (PKB); Jun-amino-terminal kinase (JNK); adenosine 5′ monophosphate-activated protein kinase (AMPK); 3T3-L1 cells; isolated mouse epididymal adipocytes.; isolated mouse epididymal adipocytes

Domaines: Biochimie, Biologie Moléculaire

Cathrine Laustrup Møller, Kirsten Raun, Marianne Lambert Jacobsen, Thomas Åskov Pedersen, Birgitte Holst, et al.. Characterization of Murine Melanocortin Receptors Mediating Adipocyte Lipolysis and Examination of Signalling Pathways Involved. Molecular and Cellular Endocrinology, 2011, 341 (1-2), pp.9. ⟨10.1016/j.mce.2011.03.010⟩. ⟨hal-00719880⟩