Neuroendocrine Control of Energy Balance

lab bench




Associate Professor of Nutritional Neuroscience

Project Summary

During the 10 weeks I participated in the PURM program this summer, I had the privilege of working in the laboratory of Dr. Matthew Hayes, as well as in collaboration with Dr. Bart DeJonghe, in their neuroscience and biobehavioral laboratories. These labs focus mainly on neural signaling pathways for chemotherapy, antiemetic treatments, and energy balance. For my project specifically, we investigated the role of the PGC1a transcription coactivator gene in energy balance. 

In previously established literature, the PGC1a transcription coactivator gene has shown to positively regulate mitochondrial metabolism, while also eliminating harmful reactive oxidative species (which are the cause for many neurodegenerative disorders). This occurs mainly in tissue with high metabolic activity such as the heart, skeletal-muscle fibres immediately involved in exercise, and the liver, making PGC1a an overall excellent target for studying oxidative metabolism. Organisms that have had the PGC1a gene selectively removed, suffer from dyslipidemia, fatty liver disease and experience extreme difficulty with exercise.  

We investigated how PGC1a is related to feeding behavior and energy balance by examining brain activation in Liver-specific PGC1a gene knockout mice [lPGC1 mice], compared to normal wild-type mice, following a peripheral injection of Cholecystokinin (CCK), a digestion and satiety peptide hormone involved in both the gastrointestinal system and in neurological pathways of energy balance. To do this, we assessed the expression of a protein, Fos, using immunohistochemistry to quantify the brain locations and numbers of neurons activated to CCK treatment.

We hypothesized that lPGC1 mice would express less Fos protein than wild type mice following CCK injection if these mutant animals were less sensitive to satiation signals. Were our hypothesis to be supported, this would mean that in addition to metabolic abnormalities in these mice, they could also be characterized to altered energy balance regulation. However, the difference between two did not follow the trend that we predicted in a significant way. Our results showed that while both strains of mice showed increased Fos expression after CCK injection [compared to vehicle saline injection], the Fos expression was comparable between strains. 

Given these data, liver PGC1a deficiency does not seem to negatively impact neuronal input to the brain from satiation signals, or at least one key signal [CCK]. Continuing to characterize potential deficits in signaling in lPGC1a mice can further the role of this gene in health. Although our findings were not expected, the experience of working in the lab consistently throughout the summer has been invaluable to me. By analyzing specific regions of the brain, learning about what solutions keep them in the optimal condition for storage and processing, studying the different regions so that I can recognize the different areas when processing them, and looking at those sliced sections under a fluorescent microscope, I have learned much more about brain anatomy than I ever thought I would. The responsibility of this summer’s independent project has helped me become intimately familiar with all of our labs’ protocols, understand them at the molecular level, and has truly shown me how the biobehavioral labs’ techniques interact to take scientists from hypothesis to conclusion. In classes during the academic year, we learn about the results of others’ discoveries and how they have impacted the way we learn. Whereas, in the lab, I learn how to reach my own discovery.