The role of the SCN clock in the regulation of leptin signaling in the brain

Project Description:

In mammals, a master circadian clock in the suprachiasmatic nucleus (SCN) synchronizes different central and peripheral tissue clocks to organize physiology and behavior across the 24-h day cycle. The adipokine hormone leptin is a major regulator of appetite and energy expenditure, acting via hypothalamic circuits. In obesity the brain becomes leptin resistant while at the same time circadian rhythms become disrupted. We hypothesize that circadian coordination of SCN-derived and feeding state-related signals determines the efficiency of leptin signaling to the brain, thus shielding the brain from a loss of leptin sensitivity and preserving its weight-controlling function under high-fat diet conditions.

 

Experimental Methods:

  • Working with genetically modified mice (knock-out mice), including breeding strategies
  • Phenotyping of mice including measurement of sleep-wake behavior, food intake, thermogenesis, energy expenditure and body weight
  • Organotypic slice cultures with long-term luminescence recordings
  • Immunohistochemical analyses
  • DNA and RNA extraction
  • PCR, qPCR, in-situ hybridization