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
  • 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].
PMID: 28096235 DOI: 10.1096/fj.201600396RR
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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