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

Miguel López-Yoldi, Kimber Stanhope, Marta Garaulet, X. Guoxia Chen, Beatriz Marcos-Gómez, María Paz Carrasco-Benso, Eva M Santa Maria, Xavier Escoté, Vivien Lee, Marinelle V. Nunez, Valentina Medici, Eduardo Martínez-Ansó, Neira Sáinz, Ana E. Huerta, Laura M. Laiglesia, Jesús Prieto, J. Alfredo Martínez, Matilde Bustos, Peter J Havel, Maria J. Moreno-Aliaga

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Cardiotrophin (CT)-1 is a regulator of glucose and lipid homeostasis. In the present study, we analyzed whetherCT-1 also acts to peripherally regulate metabolic rhythms andadipose 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-1-/-) mice (12 mo). Although circadian rhythms of VO2 were conserved in young lean CT-1-/- mice (2 mo), CT-1 deficiency caused a phase shift of the acrophase. Most of the clock genes studied (Clock, Bmal1, andPer2) displayed a circadian rhythm in adipose tissue of both wild-type (WT) and CT-1-/- mice. However, the pattern was altered in CT-1-/- mice toward a lower percentage of the rhythm or lower amplitude, especially for Bmal1 and Clock.Moreover, CT-1mRNA 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.

Original languageEnglish (US)
Pages (from-to)1639-1649
Number of pages11
JournalFASEB Journal
Volume31
Issue number4
DOIs
StatePublished - Apr 1 2017

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Keywords

  • Adipose tissue
  • Bmal1
  • Cry1
  • Obesity
  • Per2

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

López-Yoldi, M., Stanhope, K., Garaulet, M., Chen, X. G., Marcos-Gómez, B., Carrasco-Benso, M. P., Maria, E. M. S., Escoté, X., Lee, V., Nunez, M. V., Medici, V., Martínez-Ansó, E., Sáinz, N., Huerta, A. E., Laiglesia, L. M., Prieto, J., Martínez, J. A., Bustos, M., Havel, P. J., & Moreno-Aliaga, M. J. (2017). 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. FASEB Journal, 31(4), 1639-1649. https://doi.org/10.1096/fj.201600396RR