Signaling pathways implicated in alpha-melanocyte stimulating hormone-induced lipolysis in 3T3-L1 adipocytes.
Melanocortins, besides their central roles, have also recently been reported to regulate adipocyte metabolism. In this study, we attempted to characterize the mechanism underlying alpha-melanocyte-stimulating hormone (MSH)-induced lipolysis, and compared it with that of the adrenocorticotrophin hormone (ACTH) in 3T3-L1 adipocytes. Similar to ACTH, MSH treatment resulted in the release of glycerol into the cell supernatant. The activity of hormone-sensitive lipase, a rate-limiting enzyme, which is involved in lipolysis, was significantly increased by MSH treatment. In addition, a variety of kinases, including protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) were also phosphorylated as the result of MSH treatment, and their specific inhibitors caused a reduction in MSH-induced glycerol release and HSL activity, indicating that MSH-induced lipolysis was mediated by these kinases. These results suggest that PKA and ERK constitute the principal signaling pathways implicated in the MSH-induced lipolytic process via the regulation of HSL in 3T3-L1 adipocytes.
Cho
Kyung-Joo
KJ
Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon 305-600, Korea.
Shim
Jung-Hyun
JH
Cho
Min-Chul
MC
Choe
Yong-Kyung
YK
Hong
Jin-Tae
JT
Moon
Dong-Chul
DC
Kim
Jong-Wan
JW
Yoon
Do-Young
DY
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D006868:Hydrolysis / Q000187:drug effects; D008066:Lipolysis / Q000187:drug effects*; D051379:Mice; D009579:Nitrobenzoates / Q000378:metabolism; D010641:Phenotype; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics; D018043:Receptors, Corticotropin / Q000235:genetics; D044101:Receptors, Melanocortin; D015398:Signal Transduction / Q000187:drug effects*; D000521:alpha-MSH / Q000494:pharmacology*
D009579:Nitrobenzoates; D012333:RNA, Messenger; D044103:Receptor, Melanocortin, Type 2; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C086971:melanocortin 5 receptor; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone; D011494:Protein Kinases; D015056:1-Methyl-3-isobutylxanthine; C017566:4-nitroperbenzoic acid