Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression

Transl Psychiatry. 2017 Dec 8;7(12):1269. doi: 10.1038/s41398-017-0023-4.


Obesity and depression are major public health concerns, and there is increasing evidence that they share etiological mechanisms. CREB-regulated transcription coactivator 1 (CRTC1) participates in neurobiological pathways involved in both mood and energy balance regulation. Crtc1 -/- mice rapidly develop a depressive-like and obese phenotype in early adulthood, and are therefore a relevant animal model to explore possible common mechanisms underlying mood disorders and obesity. Here, the obese phenotype of male and female Crtc1 -/- mice was further characterized by investigating CRTC1's role in the homeostatic and hedonic regulation of food intake, as well as its influence on daily locomotor activity. Crtc1 -/- mice showed a strong gender difference in the homeostatic regulation of energy balance. Mutant males were hyperphagic and rapidly developed obesity on normal chow diet, whereas Crtc1 -/- females exhibited mild late-onset obesity without hyperphagia. Overeating of mutant males was accompanied by alterations in the expression of several orexigenic and anorexigenic hypothalamic genes, thus confirming a key role of CRTC1 in the central regulation of food intake. No alteration in preference and conditioned response for saccharine was observed in Crtc1 -/- mice, suggesting that mutant males' hyperphagia was not due to an altered hedonic regulation of food intake. Intriguingly, mutant males exhibited a hyperphagic behavior only during the resting (diurnal) phase of the light cycle. This abnormal feeding behavior was associated with a higher diurnal locomotor activity indicating that the lack of CRTC1 may affect circadian rhythmicity. Collectively, these findings highlight the male-specific involvement of CRTC1 in the central control of energy balance and circadian locomotor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology*
  • Depression / genetics
  • Depression / physiopathology*
  • Disease Models, Animal
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology*
  • Female
  • Hyperphagia / genetics
  • Hyperphagia / physiopathology
  • Hypothalamus / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Motor Activity / genetics
  • Motor Activity / physiology*
  • Obesity / genetics
  • Obesity / physiopathology
  • Sex Factors
  • Transcription Factors / genetics*


  • Crtc1 protein, mouse
  • Transcription Factors