We are pleased to talk with Dr. Courtney Kurtz, Associate Professor of Biology at the University of Wisconsin, Oshkosh about her research on hibernation and how her research might lead to treatments for obesity.
Ground squirrels are a natural model organism for many physiological processes. Can you tell us why you use ground squirrels in your research?
Ground squirrels are hibernators. They spend the majority of the winter in a state of torpor. This state is characterized by low metabolism and body temperature and, for many species like our model organism, no food intake. These animals live off of their fat reserves in order to stay alive through the winter. As such, they spend the majority of their active season (summer) putting on fat mass in preparation for the next hibernation season. This rapid adiposity has been shown to lead to insulin resistance late in the active season (Florant et al, 1985), very similar to what is seen in obese humans. We are examining the mechanisms of the rapid adiposity that ground squirrels undergo year after year. Our research has shown similar physiological mechanisms between fattening ground squirrels and obese humans (and other rodents). In addition, unlike laboratory mice and rats and more similar to humans, ground squirrels are not inbred and have a diverse microbiota. If we can attenuate the fattening of these ground squirrels with different interventions, these treatments may translate well to humans.
How does hibernation in ground squirrels compare to other hibernators?
Some hibernators, like chipmunks, store food for consumption during the winter arousals. Others, like bears, undergo less dramatic changes in body temperature due to their large size. Ground squirrels do not store food and instead fast throughout the winter. They periodically arouse to euthermic temperatures during the hibernation season (like many other hibernators). These torpor-arousal cycles induce dramatic fluctuations in body temperature, blood flow and white blood cell counts. One of the biggest advantages of using our species, the 13-lined ground squirrel (Ictidomys tridecemlineatus), is its size. These animals are about the size of a small rat and are therefore perfect for laboratory research.
The gut is increasingly recognized as an important contributor to both health and disease. What pathways are you studying?
We are examining the role of the gut microbiota and the gut immune system in the development of the rapid adiposity we see in the squirrels. In humans and other rodent models, obesity is induced by shifts in microbial populations in the gut. This leads to subclinical inflammation in the intestine and increased permeability of the gut barrier. This permeability allows bacterial products to enter the bloodstream and leads to inflammation in other tissues. Of particular interest are the so-called “metabolic tissues” – adipose, liver and skeletal muscle. Inflammation in these sites can promote fat accumulation and lead to the development of insulin resistance. So, although we see physiological changes in other organs, it all starts in the gut.
What is 5-Aminosalicylic Acid and how does that change gut permeability and overall health?
5-Aminosalicylic acid is a nonsteroidal anti-inflammatory drug that is gut-specific. In other words, it is not easily absorbed into the bloodstream and has primarily local responses in the gut. A study in mice (Luck et al, 2015) showed beneficial effects of this drug in obese mice. The mice on 5-ASA had a reduction in inflammatory markers in the intestine and the adipose. They also exhibited less gut permeability and better tolerance to glucose. We wanted to see if this drug would be as effective in an outbred, genetically diverse population.
What implications might your research have on other populations of mammals including humans?
We are hoping that our research will lead to new treatments for obese humans, particularly during the development of that obesity. Ground squirrels are evolutionarily programmed to fatten in the summer months – they have a strong drive to gain fat mass. If these treatments can work to curb this adiposity in the ground squirrels, they will hopefully have the same effects in humans that do not have that same “drive”.
What is your lab working on right now?
We are still working on manipulating the gut immune system to curb ground squirrel adiposity. Right now, we are analyzing data comparing 5-ASA to a steroid. These drugs both have anti-inflammatory effects in the gut but work via different mechanisms. Our goal is to determine which is a better treatment in this model. We are analyzing cytokines (pro- and anti-inflammatory) in the gut, adipose, liver and skeletal muscle of these animals. We’re also examining histology and glucose tolerance test results to determine whether the steroid worked as well as the 5-ASA.