Central regulation of CO2-induced metabolic changes of adipose tissue and its alterations in endothelial dysfunction

Project Description:

In preliminary work on the interplay between the brain and peripheral metabolism we could show that the exposure to increased CO2 levels leads to an impaired thermogenesis in brown adipose tissue (BAT) that subsequently led to a decrease of the body temperature. This effect was markedly potentiated in mice lacking a proper blood flow response to CO2 in the brain. Additionally, we have established a technique to measure BAT perfusion and by using this technique could confirm the effect of CO2 exposure on BAT activity.

The aim of the project is to figure out which mechanisms lead to the reduction of BAT activity upon CO2 exposure and whether this has any effect on metabolism. In addition to the investigations on normal mice, we will use transgenic mice that lack a proper central blood flow response to CO2 to examine the effects of an impaired removal of CO2 from the brain tissue.

Experimental Methods:

  • Working with genetically modified mice
  • Brain area-specific modulation of activity by virus-mediated and chemical approaches
  • Phenotyping of mice including measurement of thermogenesis, energy expenditure, and physical exercise
  • Perfusion measurements in brain and brown adipose tissue
  • Measurement of sympathetic nerve activity of brown fat-innervating nerves
  • Immunohistochemical and protein amount analyses