Medici, V. (Valentina)

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    Role of cardiotrophin-1 in the regulation of metabolic circadian rhythms and adipose core clock genes in mice and characterization of 24-h circulating CT-1 profiles in normal-weight and overweight/obese subjects
    (Wiley, 2017) López-Yoldi, M. (Miguel); Stanhope, K.L. (K.L.); Garaulet, M. (M.); Chen, G.X. (Guoxia X.); Marcos-Gomez, B. (Beatriz); Carrasco-Benso, M.P. (Maria Paz); Santa-Maria, E. (Eva); Escoté-Miró, X. (Xavier); Lee, V. (Vivien); Nunez, M. (Marinelle V.); Medici, V. (Valentina); Martinez-Anso, E. (Eduardo); Sainz, N. (Neira); Huerta, A. (Ana); Laiglesia-González, L.M. (Laura María); Prieto, J. (Jesús); Bustos, M. (Matilde); Havel, P.J. (P. J.); Moreno-Aliaga, M. J. (María Jesús); Martinez, J.A. (José Alfredo)
    Cardiotrophin (CT)-1 is a regulator of glucose and lipid homeostasis. In the present study, we analyzed whether CT-1 also acts to peripherally regulate metabolic rhythms and adipose tissue core clock genes inmice.Moreover, the circadian pattern of plasma CT-1 levels was evaluated in normal-weight and overweight subjects. The circadian rhythmicity of oxygen consumption rate (VO2) was disrupted in aged-obese CT-1-deficient (CT-12/2) mice (12 mo). Although circadian rhythms of VO2 were conserved in young-lean CT-12/2 mice (2 mo), CT-1 deficiency caused a phase shift of the acrophase. Most of the clock genes studied (Clock, Bmal1, and Per2) displayed a circadian rhythm in adipose tissue of both wild-type (WT) and CT-12/2 mice. However, the pattern was altered in CT-12/2 mice toward a lower percentage of the rhythm or lower amplitude, especially for Bmal1 and Clock. Moreover, CT-1 mRNA levels in adipose tissue showed significant circadian fluctuations in young WT mice. In humans, CT-1 plasma profile exhibited a 24-h circadian rhythm in normal-weight but not in overweight subjects. The 24-h pattern of CT-1 was characterized by a pronounced increase during the night (from 02:00 to 08:00). These observations suggest a potential role for CT-1 in the regulation ofmetabolic circadian rhythms.—Lopez-Yoldi,M., Stanhope, K. L., Garaulet,M., Chen, X. G.,Marcos-G ´ omez, ´ B., Carrasco-Benso, M. P., Santa Maria, E. M., Escote, X., Lee, V., Nunez, M. V., Medici, V., Mart ´ ´ınez-Anso, E., S ´ ainz, N., ´ Huerta,A.E.,Laiglesia,L.M.,Prieto, J.Mart´ınez, J.A.,Bustos,M.,Havel,P. J.,Moreno-Aliaga,M. J. Role of cardiotrophin-1 (CT-1) in the regulation of metabolic circadian rhythms and adipose core clock genes in mice and characterization of 24-h circulating CT-1 profiles in normal-weight and overweight/obese subjects