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. Epub 2017 Jan 17.

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.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism*
  • Adipose Tissue / physiology
  • Adolescent
  • Adult
  • Animals
  • CLOCK Proteins / genetics*
  • CLOCK Proteins / metabolism
  • Circadian Rhythm*
  • Cytokines / blood
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / blood
  • Obesity / metabolism*
  • Oxygen Consumption

Substances

  • Cytokines
  • cardiotrophin 1
  • CLOCK Proteins