title: Apelin inhibits adipogenesis and lipolysis through distinct molecular pathways.
abstract: Apelin is an adipokine secreted by adipocytes. Co-expression of apelin and apelin receptor (APJ) in adipocytes implies the autocrine regulations of apelin on adipocyte functions through yet unknown molecular mechanisms. In the present study, we provide evidence that apelin, through its interaction with APJ receptor, inhibits adipogenesis of pre-adipocytes and lipolysis in mature adipocytes. The detailed molecular pathways underlying apelin signaling is proposed based on our experimental observations. Specifically, we show that apelin suppresses adipogenesis through MAPK kinase/ERK dependent pathways. And by preventing lipid droplet fragmentation, apelin inhibits basal lipolysis through AMP kinase dependent enhancement of perilipin expression and inhibits hormone-stimulated acute lipolysis through decreasing perilipin phosphorylation. Apelin induced decrease of free fatty acid release can be attributed to its dual inhibition on adipogenesis and lipolysis. This study suggests that the autocrine signaling of apelin may serve as a novel therapeutic target for obesity and other metabolic disorders.
authors: Division of Bioengineering, Nanyang Technological University, Singapore 637457, Singapore.
authors: Aung
authors: A
authors: Than
authors: Yiqi
authors: Y
authors: Cheng
authors: Li-Chern
authors: LC
authors: Foh
authors: Melvin Khee-Shing
authors: MK
authors: Leow
authors: Su Chi
authors: SC
authors: Lim
authors: Yon Jin
authors: YJ
authors: Chuah
authors: Yuejun
authors: Y
authors: Kang
authors: Peng
authors: P
authors: Chen
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis; D054392:Adipokines; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D019898:Autocrine Communication; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D025461:Feedback, Physiological; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050356:Lipid Metabolism; D008066:Lipolysis; D020935:MAP Kinase Signaling System; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D050151:Subcutaneous Fat / Q000166:cytology
chemical_list: D054392:Adipokines; D000073861:Apelin; D000075244:Apelin Receptors; C402826:Apln protein, mouse; C491285:Aplnr protein, mouse; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; D002352:Carrier Proteins; D005419:Flavonoids; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; D000070778:Perilipin-1; D010750:Phosphoproteins; D043562:Receptors, G-Protein-Coupled; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one