Cardiotrophin-1 Is a Key Regulator of Glucose and Lipid Metabolism

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 treat...

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Bibliographic Details
Published in:Cell metabolism 2011-08, Vol.14 (2), p.242-253
Main 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
Format: Article
Language:English
Subjects:
Adipose Tissue, White - metabolism
Animals
Body Weight
Cytokines - deficiency
Cytokines - metabolism
Cytokines - pharmacology
Eating
Energy Metabolism
Fatty Acids - metabolism
Glucose - metabolism
Hypercholesterolemia - genetics
Insulin Resistance - genetics
Lipid Metabolism - drug effects
Mice
Mice, Inbred C57BL
Mice, Transgenic
Obesity - genetics
Oxidation-Reduction
Phosphorylation
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Summary: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. ► Mature ct-1 −/− mice develop obesity, insulin resistance, and hypercholesterolemia ► rCT-1 promotes fat utilization in WAT and boosts FFA oxidation in muscle by AMPKα2 ► rCT-1 has glucose-lowering effects and increases insulin-stimulated pAKT in muscle ► rCT-1 treatment reduces body weight and corrects insulin resistance in obese mice
ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2011.05.013