title: Cardiotrophin-1 is a key regulator of glucose and lipid metabolism.
abstract: Cardiotrophin-1 (CT-1) is a member of the gp130 family of cytokines. We observed that ct-1(-/-) mice develop mature-onset obesity, insulin resistance, and hypercholesterolemia despite reduced calorie intake. Decreased energy expenditure preceded and accompanied the development of obesity. Acute treatment with rCT-1 decreased blood glucose in an insulin-independent manner and increased insulin-stimulated AKT phosphorylation in muscle. These changes were associated with stimulation of fatty acid oxidation, an effect that was absent in AMPKα2(-/-) mice. Chronic rCT-1 treatment reduced food intake, enhanced energy expenditure, and induced white adipose tissue remodeling characterized by upregulation of genes implicated in the control of lipolysis, fatty acid oxidation, and mitochondrial biogenesis and genes typifying brown fat phenotype. Moreover, rCT-1 reduced body weight and corrected insulin resistance in ob/ob and in high-fat-fed obese mice. We conclude that CT-1 is a master regulator of fat and glucose metabolism with potential applications for treatment of obesity and insulin resistance.
authors.affiliation: Department of Nutrition, Food Sciences, Physiology and Toxicology, University of Navarra, 31008 Pamplona, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Moreno-Aliaga
authors.forename: Nerea
authors.initials: N
authors.lastname: Pérez-Echarri
authors.forename: Beatriz
authors.initials: B
authors.lastname: Marcos-Gómez
authors.forename: Eduardo
authors.initials: E
authors.lastname: Larequi
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Gil-Bea
authors.forename: Benoit
authors.initials: B
authors.lastname: Viollet
authors.forename: Ignacio
authors.initials: I
authors.lastname: Gimenez
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martínez
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
authors.forename: Matilde
authors.initials: M
authors.lastname: Bustos
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D016207:Cytokines / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D004435:Eating; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006937:Hypercholesterolemia / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics; D010084:Oxidation-Reduction; D010766:Phosphorylation
chemical_list: D016207:Cytokines; D005227:Fatty Acids; C092073:cardiotrophin 1; D005947:Glucose