Author(s):
Rodrigues, Adriana 
; Almeida, Henrique ; Gouveia, Alexandra
Date: 2009
Persistent ID: http://hdl.handle.net/10216/20511
Origin: Repositório Aberto da Universidade do Porto
Subject(s): Ciências da Saúde
Document details
Melanocortin signalling in fat cells
Description
Melanocortin peptides and their receptors have long been known to affect the central control of food intake and body weight, thus playing a critical role in the development of obesity [1]. The melanocortin 5 receptor (MC5R) has been directly linked with lipid metabolism in peripheral tissues: MC5R deletion in mouse generates defects in sebaceous gland secretion [1] and MC5R stimulation increases fatty acid oxidation in muscle cells [2]. In this study, we tackled the role of MC5R in lipolysis and adipocyte function using the well established model of differentiated mouse 3T3-L1 adipocytes. Cell-signalling based experiments were performed after adipocyte treatment with alpha-melanocyte-stimulating hormone (alpha-MSH) and compared with the MC5R specific activation previously described in HEK293 [3] and HeLa cells stably transfected with MC5R-GFP. Adipocyte response to alpha-MSH resulted in a loss of cytoplasmatic lipid content and release of glycerol into the cell medium by an ERK1/2 dependent mechanism. Moreover, downstream of ERK1/2, alpha-MSH induces p90RSK and CREB phosphorylation and c-Fos expression. The correlation between alpha-MSH action in 3T3-L1 adipocytes and the specific signalling pathways underlying MC5R activation, strongly suggests that lipolysis is mediated by this receptor. [1] Cone RD (2006) Endocr Rev 27(7):736:49 [2] An et al (2007) J Biol Chem 282(5):2862-70 [3] Rodrigues et al (2009) Mol Cell Endocrinol 303:74-81 [resumo]
Melanocortin peptides and their receptors have long been known to affect the central control of food intake and body weight, thus playing a critical role in the development of obesity [1]. The melanocortin 5 receptor (MC5R) has been directly linked with lipid metabolism in peripheral tissues: MC5R deletion in mouse generates defects in sebaceous gland secretion [1] and MC5R stimulation increases fatty acid oxidation in muscle cells [2]. In this study, we tackled the role of MC5R in lipolysis and adipocyte function using the well established model of differentiated mouse 3T3-L1 adipocytes. Cell-signalling based experiments were performed after adipocyte treatment with alpha-melanocyte-stimulating hormone (alpha-MSH) and compared with the MC5R specific activation previously described in HEK293 [3] and HeLa cells stably transfected with MC5R-GFP. Adipocyte response to alpha-MSH resulted in a loss of cytoplasmatic lipid content and release of glycerol into the cell medium by an ERK1/2 dependent mechanism. Moreover, downstream of ERK1/2, alpha-MSH induces p90RSK and CREB phosphorylation and c-Fos expression. The correlation between alpha-MSH action in 3T3-L1 adipocytes and the specific signalling pathways underlying MC5R activation, strongly suggests that lipolysis is mediated by this receptor. [1] Cone RD (2006) Endocr Rev 27(7):736:49 [2] An et al (2007) J Biol Chem 282(5):2862-70 [3] Rodrigues et al (2009) Mol Cell Endocrinol 303:74-81 [resumo]
Document Type
Article
Language English
Language English
| Financiadores do RCAAP | |||||||
|
|
|
|
|
|
||