alfa-MSH signalling via melanocortin 5 receptor promotes lipolysis and impairs re-esterification in adipocytes

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Rodrigues, Adriana (Author) FCNAUP; Almeida, Henrique (Author) FCNAUP; Gouveia, Alexandra (Author) FCNAUP

Journal

Title: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

Vol. 1831 No. 7

Pages: 1267-1275

ISSN: 1388-1981

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 29 Citations

ISI Web of Science

Scopus - 31 Citations

Scientific classification

FOS: Medical and Health sciences > Health sciences

CORDIS: Health sciences

Other information

Authenticus ID: P-006-9K0

DOI: 10.1016/j.bbalip.2013.04.008

Abstract (EN): The melanocortin system has a clear effect on the mobilisation of stored lipids in adipocytes. The aim of the current study was to investigate the role of melanocortin 5 receptor (MC5R) on alpha-melanocyte-stimulating hormone (alpha-MSH)-induced lipolysis in 3T3-L1 adipocytes. To this end, MC5R expression was decreased by small interfering RNA (siRNA), which significantly impaired the alpha-MSH stimulation of lipolysis, as determined by glycerol and nonesterified fatty-acid (NEFA) quantification. The functional role of alpha-MSH/MC5R on triglyceride (TG) hydrolysis was mediated by hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), perilipin 1 (PLIN1) and acetyl-CoA carboxylase (ACC). Immunofluorescence microscopy revealed that phosphorylated HSL clearly surrounded lipid droplets in alpha-MSH-stimulated adipocytes, whereas PLIN1 left the immediate periphery of lipids. These observations were lost when the expression of MC5R was suppressed. In 3T3-L1 adipocytes, alpha-MSH-activated MC5R signals through the cAMP/PKA and MAPK/ERK1/2 pathways. PICA was fundamental for HSL and PLIN1 activation and lipolysis regulation. ERK1/2 inhibition strongly interfered with the release of NEFAs but not glycerol. In addition, the intracellular TG levels, which were decreased after MC5R activation, were restored after ERK1/2 inhibition, indicating that these kinases are involved in NEFA re-esterification rather than lipolysis regulation. This notion is also supported by the observation that the alpha-MSH-mediated activation of phosphoenolpyruvate carboxykinase (PEPCK) was abolished in the presence of ERK1/2 inhibitors. Altogether, these results indicate that alpha-MSH-activated MC5R regulates two tightly coupled pathways in adipocytes: lipolysis and re-esterification. The global effect is a decrease in adipocyte fat mass, which is important for strategies to ameliorate obesity.

Language: English

Type (Professor's evaluation): Scientific

Notes: <a href="http://gateway.isiknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS&DestLinkType=FullRecord&KeyUT=:000320497100009">Indexado na ISI Web of Science</a>