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