Cardiotrophin-1 Regulates Adipokine Production in 3T3-L1 Adipocytes and Adipose Tissue From Obese Mice.
Cardiotrophin-1 (CT-1) belongs to the IL-6 family of cytokines. Previous studies of our group revealed that CT-1 is a key regulator of glucose and lipid metabolism. The aim of the present study was to analyze the in vitro and in vivo effects of CT-1 on the production of several adipokines involved in body weight regulation, nutrient metabolism, and inflammation. For this purpose, 3T3-L1 adipocytes were incubated with recombinant protein CT-1 (rCT-1) (1-40 ng/ml) for 1 and 18 h. Moreover, the acute effects of rCT-1 administration (0.2 mg/kg, i.v.) for 30 min and 3 h on adipokines levels were also evaluated in high-fat fed obese mice. In 3T3-L1 adipocytes, rCT-1 treatment downregulated the expression and secretion of leptin, resistin, and visfatin. However, rCT-1 significantly stimulated apelin mRNA and secretion. rCT-1 (18 h) also promoted the activation by phosphorylation of AKT, ERK 1/2, and STAT3. Interestingly, pre-treatment with the PI3K inhibitor LY294002 reversed the stimulatory effects of rCT-1 on apelin expression, suggesting that this pathway could be mediating the effects of rCT-1 on apelin production. In contrast, acute administration of rCT-1 (30 min and 3 h) to diet-induced obese mice downregulated leptin and resistin, without significantly modifying apelin or visfatin mRNA in adipose tissue. Furthermore, CT-1 null mice exhibited altered expression of adipokines in adipose tissue. The present study demonstrates that rCT-1 modulates the production of adipokines in vitro and in vivo, suggesting that the regulation of the secretory function of adipocytes could be involved in the metabolic actions of this cytokine. J. Cell. Physiol. 232: 2469-2477, 2017. © 2016 Wiley Periodicals, Inc.
Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Navarra, Spain.|Centre for Nutrition Research, University of Navarra, Pamplona, Navarra, Spain.
Miguel
M
López-Yoldi
Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Navarra, Spain.
Beatriz
B
Marcos-Gomez
Department of Hepatology and Gene Therapy, CIMA, University of Navarra, Pamplona, Navarra, Spain.
María Asunción
MA
Romero-Lozano
Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Navarra, Spain.|Centre for Nutrition Research, University of Navarra, Pamplona, Navarra, Spain.
Neira
N
Sáinz
Department of Hepatology and Gene Therapy, CIMA, University of Navarra, Pamplona, Navarra, Spain.|CIBERehd, Institute of Health Carlos III, Madrid, Spain.
Jesús
J
Prieto
Department 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.|IdiSNA, Navarra's Health Research Institute, Pamplona, Spain.
Jose Alfredo
JA
Martínez
Department of Hepatology and Gene Therapy, CIMA, University of Navarra, Pamplona, Navarra, Spain.
Matilde
M
Bustos
Department 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.|IdiSNA, Navarra's Health Research Institute, Pamplona, Spain.
Maria J
MJ
Moreno-Aliaga
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D000073861:Apelin; D016207:Cytokines / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D052243:Resistin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D052243:Resistin; C499623:Retn protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C092073:cardiotrophin 1; D054409:Nicotinamide Phosphoribosyltransferase; C495867:nicotinamide phosphoribosyltransferase, mouse; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases