The Secor Laboratory of Evolutionary and Integrative Physiology

at the University of Alabama

 

Python model

 

The Burmese python (Python molurus), native to southeast Asia, and is one of the largest snakes species in the world reaching lengths of 7 meters and a mass exceeding 100 kg. The development of the Burmese python as a research model evolved from a study on the digestive responses of the infrequently feeding snake, the sidewinder rattlesnake (Crotalus cerastes). In a study coauthored by Eric Stein, Jared Diamond, and myself we discovered that sidewinders dramatically upregulate intestinal performance after feeding and then downregulate intestinal function and morphology once digestion was completed. This response was matched with an unprecedented increase (8-fold) in metabolic rate during digestion. While these findings were exciting and sparked ideas for new studies, sidewinders can only be obtained from the wild and as rattlesnakes are venomous. Given the efforts needed to acquire more sidewinders for research and the management issues and risks of housing and working with a venomous snake, I searched for an alternative snake to study. I compared postfeeding responses of several species of snakes and found the Burmese python, which also feeds infrequently in the wild, to exhibit similar magnitudes of physiological responses as the sidewinders. Additionally, Burmese pythons are not venomous, generally very docile, and are produced commercially for the pet trade. They are easy to maintain, can be feed once every week or two, and like rodents can be housed in commercial rack systems.

 

Since 1993, my studies on the Burmese pythons have explored a variety of physiological responses to long-term fasting and feeding. For the python, fasting triggers an integrative downregulation of tissue performance. We have proposed that this response serves to reduce their metabolism, thereby decreasing energy expenditure during their long bouts between meals. Support for this hypothesis is that the standard metabolic rates of the Burmese pythons (as well as other snakes that feed infrequently) are lower than those snakes that feed frequently and don't widely regulate intestinal performance with feeding and fasting. Given that during fasting physiological performance in pythons is downregulated, performance is then rapidly upregulated with feeding. The magnitude by which the python regulates performance with feeding is much greater than the changes documented with feeding for more traditional animal research models (mice, rats, rabbits).

 

 

 

Our work and those of our collaborators have focused on three integrative responses of the python to feeding; metabolic, gastrointestinal, and cardiovascular.

 

Metabolic: The large postprandial increase in metabolic rate for the Burmese python was first observed by Francis Benedict at the turn of the twentieth century. We likewise found the python to exhibit the largest relative scope in postprandial metabolism of any studied organism. In fact the magnitude of their postprandial metabolism was found to increase with meals size, such that when digesting meals equaling their body mass, they experience a 44-fold increase in metabolic rate. The only known prior example of such of an increase in metabolism was that experienced by racehorses during a full gallop. Whereas high rates of metabolism experienced during exercise are short-lived for most organisms, pythons can maintain elevated levels of metabolism for days during digestion. We have explored the possible mechanisms for fueling such high levels of metabolism and have found python to experience tremendous postfeeding increases (> 150-fold) in plasma concentration of triglycerides (> 1500 mg/dL). Originating from body fat stores and the meal, these circulating lipids would be valuable source of energy for fueling meal digestion.

 


Gastrointestinal: Feeding triggers the quiescent stomach and small intestine to rapidly upregulate performance. Within hours, the stomach begins to produce hydrochloric acid resulting in a drop of gastric pH from 7.5 to 2. Gastric pH is maintained around 1.5 for the duration (as much as 10 days) of gastric breakdown. Simultaneously, the small intestine responds both morphologically and functionally. Within 24 hours after feeding the intestinal has doubled in mass, as intestinal enterocytes increase in volume by 50%. Functional surface area is increased with the lengthening of the villi and the unprecedented 5-fold increase in the length of the microvilli. Matched with these trophic responses is the rapid upregulation of nutrient transport as amino acid and glucose transport rates increase by 5 to 10-fold. These integrative responses generate a 10 to 20-fold increase in total small intestinal performance to absorb nutrients. Given that mammal models can regulate intestinal performance over a 2-fold range, the python is an unmatched model for studying the underlying mechanisms responsible for trophic and functional responses of the small intestine.

 


Cardiovascular
: The large demand for digestive performance in the python is supported by the postprandial upregulation in their cardiovascular performance. During digestion, python experience a 4 to 5-fold increase in cardiac output, whereas during exercise cardiac output in these snakes increases by only 3 to 4-fold. As demand on the gut is increased with larger meals, pythons respond by further increasing cardiac output until it reaches a plateau with meals larger than 35% of their body mass. As expected, blood flow to the gut increases for the python, superior mesenteric flow and hepatic portal flow increase as much as 11- and 16-fold, respectively, which is the large relative increase yet documented for the postprandial gut. For the python, we have documented a 40% increase in heart mass after feeding, as well as increases in cardiac metabolism and metabolic machinery. The advantage of the python model for studies in cardiac performance is that the metabolic demand that generates the increase in performance is digestion, which is non-fatiguing. In contrast, studies that use exercise to elevate cardiac performance are hindered by the physiological limitations of fatigue-prone skeletal muscles. Therefore we can maintained elevated levels of cardiac performance (without fatiguing) in these snakes, as well as demonstrate that their cardiac performance can exceed that during exercise, and thus is not a limiting factor in determining maximum rates of metabolism experienced during exercise. The python' rapid postprandial heart growth provides a unique opportunity to examine the signals and mechanisms underlying cardiac hypertrophy. Cardiac hypertrophy occurs in response to either volume overload (physiological cardiac hypertrophy) or pressure overload (pathological cardiac hypertrophy). Physiological cardiac hypertrophy characterizes heart growth of athletes, whereas pathological cardiac hypertrophy is a feature of human heart disease. Given the interest in deciphering the signals and mechanisms of human cardiac hypertrophy, we are developing the python as a new model of cardiac hypertrophy.

 

 

The Burmese python is certainly not on the top of most scientists' list of research models, but by possessing the unique capacity to widely regulate physiological performance beyond that experienced by mammal models; they are unmatched for exploring the signaling mechanisms and cellular pathways of tissue response. Consider that they are relatively easy to care for (less costly than similar-size mammals), amendable to a variety of surgical treatments, and only need to eat to generate a response. Interest in this research model has expanded in the past decade with this python being used in research laboratory in California, Colorado, Canada, Denmark, France, and Germany.