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Cardiotrophin-1 is a key regulator of glucose and lipid metabolism
Authors:Moreno-Aliaga María J  Pérez-Echarri Nerea  Marcos-Gómez Beatriz  Larequi Eduardo  Gil-Bea Francisco Javier  Viollet Benoit  Gimenez Ignacio  Martínez J Alfredo  Prieto Jesús  Bustos Matilde
Institution:Department of Nutrition, Food Sciences, Physiology and Toxicology, University of Navarra, 31008 Pamplona, Spain.
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.
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