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  2. 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

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 J. 2017 Apr;31(4):1639-1649. doi: 10.1096/fj.201600396RR.
Miguel López-Yoldi 1 2 Kimber L Stanhope 3 Marta Garaulet 4 X Guoxia Chen 3 Beatriz Marcos-Gómez 1 María Paz Carrasco-Benso 4 Eva M Santa Maria 5 Xavier Escoté 1 2 Vivien Lee 3 Marinelle V Nunez 3 Valentina Medici 3 Eduardo Martínez-Ansó 6 Neira Sáinz 1 2 Ana E Huerta 1 2 Laura M Laiglesia 1 2 Jesús Prieto 5 6 J Alfredo Martínez 1 2 7 8 Matilde Bustos 6 Peter J Havel 3 Maria J Moreno-Aliaga 9 2 7 8
Affiliations

Affiliations

  • 1 Department of Nutrition, Food Science, and Physiology, University of Navarra, Pamplona, Spain.
  • 2 Centre for Nutrition Research, University of Navarra, Pamplona, Spain.
  • 3 Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
  • 4 Department of Physiology, Faculty of Biology, University of Murcia, Murcia, Spain.
  • 5 Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd) and Institute of Health Carlos III, Madrid, Spain.
  • 6 Department of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
  • 7 Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain; and.
  • 8 Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
  • 9 Department of Nutrition, Food Science, and Physiology, University of Navarra, Pamplona, Spain; [email protected].
Abstract

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 in mice. 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, and Per2) 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-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 of metabolic circadian rhythms.-López-Yoldi, M., Stanhope, K. L., Garaulet, M., Chen, X. G., Marcos-Gómez, B., Carrasco-Benso, M. P., Santa Maria, E. M., 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. 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.

Keywords

Bmal1; Cry1; Per2; adipose tissue; obesity.

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