title: Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipases.
abstract: Cardiotrophin-1 (CT-1) is a cytokine with antiobesity properties and with a role in lipid metabolism regulation and adipose tissue function. The aim of this study was to analyze the molecular mechanisms involved in the lipolytic actions of CT-1 in adipocytes. Recombinant CT-1 (rCT-1) effects on the main proteins and signaling pathways involved in the regulation of lipolysis were evaluated in 3T3-L1 adipocytes and in mice. rCT-1 treatment stimulated basal glycerol release in a concentration- and time-dependent manner in 3T3-L1 adipocytes. rCT-1 (20 ng/ml for 24 h) raised cAMP levels, and in parallel increased protein kinase (PK)A-mediated phosphorylation of perilipin and hormone sensitive lipase (HSL) at Ser660. siRNA knock-down of HSL or PKA, as well as pretreatment with the PKA inhibitor H89, blunted the CT-1-induced lipolysis, suggesting that the lipolytic action of CT-1 in adipocytes is mainly mediated by activation of HSL through the PKA pathway. In ob/ob mice, acute rCT-1 treatment also promoted PKA-mediated phosphorylation of perilipin and HSL at Ser660 and Ser563, and increased adipose triglyceride lipase (desnutrin) content in adipose tissue. These results showed that the ability of CT-1 to regulate the activity of the main lipases underlies the lipolytic action of this cytokine in vitro and in vivo, and could contribute to CT-1 antiobesity effects.
authors.affiliation: Departments of Nutrition, Food Science, and Physiology University of Navarra, Pamplona, Navarra, Spain Centre for Nutrition Research, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Yoldi
authors.affiliation: Departments of Nutrition, Food Science, and Physiology University of Navarra, Pamplona, Navarra, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Fernández-Galilea
authors.affiliation: Departments of Nutrition, Food Science, and Physiology University of Navarra, Pamplona, Navarra, Spain Centre for Nutrition Research, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Laiglesia
authors.affiliation: Gene Therapy and Hepatology, CIMA, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Larequi
authors.affiliation: Gene Therapy and Hepatology, CIMA, University of Navarra, Pamplona, Navarra, Spain CIBERehd Institute of Health Carlos III, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
authors.affiliation: Departments of Nutrition, Food Science, and Physiology University of Navarra, Pamplona, Navarra, Spain Centre for Nutrition Research, University of Navarra, Pamplona, Navarra, Spain CIBERobn, Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martínez
authors.affiliation: Gene Therapy and Hepatology, CIMA, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Bustos
authors.affiliation: Departments of Nutrition, Food Science, and Physiology University of Navarra, Pamplona, Navarra, Spain Centre for Nutrition Research, University of Navarra, Pamplona, Navarra, Spain CIBERobn, Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Moreno-Aliaga
mesh_terms: D041721:3T3-L1 Cells; D052438:Adipocytes, White / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000819:agonists / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D020868:Gene Silencing; D008049:Lipase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000096:biosynthesis / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D002787:Sterol Esterase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D000217:Acyltransferases
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D016207:Cytokines; D020536:Enzyme Activators; D008049:Lipase; D000070778:Perilipin-1; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D002787:Sterol Esterase; C508072:G0S2 protein, mouse; C092073:cardiotrophin 1; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases
keywords: adipocytes; adipose triglyceride lipase; cell signaling; cytokines; hormone-sensitive lipase; obesity; perilipin; protein kinase A