In Fall 2014, the focus of The Python Project shifted from heart and liver to adipose tissue with the aim of identifying the role of genes that regulate how fatty acids are stored and released from adipose tissue. The Burmese python can eat a meal up to 75% of their body weight, and after feeding, lipids accumulate in the serum at a concentration that would be lethal to a mammal. The source of the lipids is currently unclear. Although it is likely that a significant amount of lipids comes from the meal itself, the increase occurs at a time when the meal is only partially digested, suggested a second source of lipids. Adipose tissue is a likely candidate despite the relatively low amount of stored fat the Burmese python has. To better understand the role of adipose tissue as either a source of serum lipids or destination for dietary lipids, students in Fall 2014 examined expression of a set of genes that regulate fatty acid transport and metabolism in fat bodies harvested from fasted pythons and at several time point after feeding.*
Lipid metabolism is an important mechanism by which organisms break down fatty acids into smaller compounds in order to yield energy for cellular processes. Many different enzymes in the body catalyze this metabolism, and abnormalities in these enzymes cause a buildup of lipids that can ultimately result in metabolic disorders in humans, and damage organs. By examining expression of adipokines, for example, released from adipose tissue at various days post-fed, we should be able to better understand the python’s cell signaling mechanisms that are important in infection, inflammation, and immune response. Adipokines may also help us understand how the python does not become obese or develop metabolic syndrome, which is characterized by insulin resistance, diabetes mellitus, and cardiovascular disease, after eating a meal that can be up to 75% the body weight of the animal. Humans who have a high number of circulating triglycerides are usually obese, and either have or will develop some or all of the metabolic syndrome characteristics.*
Students in Fall 2014 measured genes that encode adipokines and enzymes that are involved in both the storage and release of lipids from adipose tissue. They found that genes that mediate the storage of excess lipids after feeding like Diglyceride acyltransferase (DGAT) are decreased, likely to provide energy to organs that are participating in digestion. However, enzymes that participate in the liberation of lipids from adipose tissue like Carnitine Palmitoyl Transferase 1A (CPT1A), and Patatin-like Phospholipase Domain Containing 2 (PNPLA2) lipase were dramatically increased at one day after feeding, whereas those that participate . This was the earliest time point examined and coincides with when the serum lipids are highest in the python. Because digestion takes place between one and six days after feeding it seems likely that at least some of the lipids observed in the serum at one day after feeding originate in the adipose tissue. Interestingly, for the third semester, we were unable to measure cytokines like interleukins and interferon, suggesting that a lack of these proteins could prevent the development of disorders resulting from systemic inflammation when serum lipids are high.
*Adapted from the final research paper of Danielle Krause, student in the Fall 2014 Python Project.