Our long-term programs aim to examine why there is an apparent dichotomy in the regulation of gastrointestinal performance among ectotherms and to identify how tissues are able to respond both functionally and structurally to changes in demand. For the first program, we take a comparative approach working with a wide array of fishes, amphibians, and reptiles to explore the correlation between feeding habits with regulation of gastrointestinal performance and metabolic rate. To investigate the underlying mechanisms of how tissue respond, we rely primarily on our model system, the Burmese python and employ a variety of tissue, cellular and molecular techniques to describe the signaling and cellular mechanisms of tissue plasticity. The following briefly describes the major studies being undertaken in my laboratory and our collaborative projects.
- Adaptive interplay between feeding ecology and digestive physiology:
This long-term project investigates the adaptive interplay between feeding ecology and digestive physiology among fishes, amphibians and reptiles. The work strives to demonstrate the link between feeding frequency and the magnitude by which digestive performance is regulated. This program has involved over 55 different species of fishes, amphibians, and reptiles, and has found that species that feed relatively frequently in the wild regulate their intestinal performance very modestly, whereas those species that naturally experience long intervals between meals regulate their intestinal performance over a much greater range. We have found that the capacity to widely regulate intestinal performance has evolved independently at least five times among amphibians and reptiles. It is hypothesized that the selective pressure underlying the evolution of the wide regulation of gastrointestinal performance for infrequently feeding vertebrates resides in the conservation of energy during long periods of fasting. We continue to explore gastrointestinal responses to fasting and feeding with a recent focus on fishes and several snake families (boidae, pythonidae, and colubridae) that exhibit a broad continuum of feeding habits.
- Specific dynamic action:
- Specific dynamic action is the cumulative energy expended on all processes involved in meal digestion and assimilation, and is characterized by the postprandial increase in metabolic rate. We have characterized the SDA responses for over 60 species of amphibians and reptiles with a focus on identifying the effects of meal size, meal type, meal composition, body temperature, and body size on this physiological response. We have found among a variety of taxa that larger meals and meals more difficult to digest generate larger SDA responses.
- Allometry of digestive performance:
Body mass has a significant effect on the size and performance of all organs, as well as on metabolic rate. Whereas much attention has been on the allometry of tissues size and resting and maximum rates of metabolism, few studies have explored the scaling of digestive performance or metabolism, either intraspecifically or interspecifically. Several of our projects are aimed at characterizing the allometry of specific dynamic action (cost of digestion) and intestinal performance (total intestinal nutrient uptake capacity) interspecifically for anurans and colubrid snakes, and intraspecifically for the marine toad (Bufo marinus) and diamondback water snake (Nerodia rhombifer).
- Determinants of individual variation in metabolic rates:
- Biologists are well familiar with the individual variation in metabolic rates that are independent of activity, body size and temperature. We hypothesize that individual differences in the mass of certain organs is an important underlying source of the individual variation in metabolic rates. This hypothesis is based on the knowledge that organs differ in their metabolic rate. We are testing the prediction that those individuals with larger than predicted organs of high metabolic rates (heart, kidney, liver) will exhibit higher than predicted standard and activity metabolic rates. We are investigating this interaction between organ size and metabolic rates using the diamondback water snake (Nerodia rhombifer).
Integrative mechanisms of tissue response
- Regulation of gastric acid production:
- Mammals constantly produce gastric acid and hence continuously maintain a very acidic environment within their stomach even during periods of fasting. In contrast, pythons shut down acid production upon the completion of digestion and then rapidly turn on acid production with feeding. Pythons produce enough acid to breakdown an intact meal while maintaining a gastric pH of 1.5 for 4-8 days. Once all of the meal has exited the stomach, acid production ceases, and gastric pH return to normality. The snake’s ability to widely regulate acid production maybe unique among animals, therefore we are examining the morphological and cellular changes of the python's gastric epithelium that underlie this trait.
- Mechanisms underlying the regulation of intestinal performance:
- For the python, feeding triggers the dramatic upregulate of small intestinal capacity to transport nutrients, a product of a doubling of small intestinal mass and 5- to 10-fold increases in mass-specific rates of nutrient uptake. Highlights of the morphological response are a doubling of enterocyte volume and a 5-fold increase in microvillus length. Functionally, python intestines are sensitive to digestive demand, increasing rates of nutrient transport rates with larger meals. While there are many proximal signals known to trigger intestinal response, it appears for the python that luminal nutrients, specifically amino acids, are responsible for inducing the upregulation of performance. A NSF-funded project investigated the cellular mechanisms underlying the regulation of python intestinal performance, with a specific focus on whether the modulation of microvilli length is the key mechanism by which intestinal function is altered.
- Capacity of cardiovascular performance:
- Matching the python's large postprandial increase in metabolism and digestive performance is an increase in their cardiovascular performance. During the digestion of a rodent meal equaling 25% of the snake's body mass, pythons experience 3.5-fold increase in heart rate and a 5-fold increase in cardiac output. Both of these increases exceed the increase in heart rate and cardiac output that pythons experience with crawling. Feeding also generates unprecedented 11-fold and 16-fold increases in superior mesenteric artery flow and hepatic portal flow. If forced to crawl while digesting, blood flow to the intestine drops by 85% as blood is shunted away from the gut to axial muscles. Pythons respond to an increase in meal size and thus an increase in cardiac demand by increasing heart rate and cardiac output. This demonstrates that the python’s heart has the capacity to increase performance beyond that dictated by strenuous activity.
- Cardiac hypertrophy:
- In response to the continuous high demands on the python's heart during digestion, the heart grows. Within three days after feeding, the python's heart has increased in mass by as much as 35%. This physiological hypertrophy of the python's heart is similar to that experienced by human athletes with the exception that it only takes a few days for the python, rather than months and years for the athlete. We are examining how meal size and composition impacts cardiac hypertrophy and the morphological elements responsible for the growth. We are also developing a pathological model of cardiac hypertrophy using the python. Pathological cardiac hypertrophy results from pressure overload and is characteristic of human heart disease. We are inducing pressure overload in pythons by completely ligating their left systemic artery, thereby forcing all of their left ventricular output into their right systemic artery. This technique results in a 25% increase in ventricular mass for pythons.
- Dr. Tim Nagy, Department of Nutrition Science, University of Alabama at Birmingham
- We are examining the postprandial mobilization of lipids for the Burmese python and using non-invasive methods to estimate body fat content in amphibians and reptiles. We have found that pythons experience tremendous postfeeding increases (by 150-fold) in plasma concentrations of triglycerides. While the source of these lipids is shared between meal and body fat stores, we have found that triglyceride levels still increase significantly even during the digestion of a low-fat meal. We are also working on the non-invasive determination of body fat stores for amphibians and reptiles using dual-energy X-ray absorptiometry (DEXA) and CT scan. We have found these techniques to be the most accurate in estimating (non-invasively) fat content for these animals.
- Dr. Jean-Herve Lignot, Centre d'Ecologie et Physiologie Energétiques, Strasbourg, France
- We are investigating the morphological as well as functional changes of the gastrointestinal epithelium of the pythons with feeding and fasting using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and immunocytochemistry. This work has lead to the potential discovery of a unique cell type in the intestines of vertebrates that is involved in calcium release. We are also examining the effects of meal composition on intestinal response and postprandial thermogenesis in python.
- Dr. Robert Espinoza, Department of Biology, California State University, Northridge
- We are assisting Dr. Espinoza's lab in investigating the morphological and functional responses of the digestive tract to diet switching in lizards. We have thus far collaborated on projects involving desert iguana (Dipsosaurus dorsalis) and bearded dragons (Pogona vitticeps).
- Dr. Dale DeNardo, School of Life Sciences, Arizona State University
- We've worked with Dr. DeNardo's lab to explore for Gila monsters the regulatory role of their saliva protein Exendin-4 on digestive performance. Exendin-4 when administered to diabetic mammalian model stimulates insulin production and lowers blood glucose levels. Presently unknown is the function of this protein for the Gila monster.
- Dr. Richard Wrangham, Department of Anthropology, Harvard University
- Dr. Wrangham has proposed that the onset of meal cooking in human evolution, and thus the reduction in eating effort, lead to a number of beneficial social and life history advances. We are investigating the differences in the cost of meal digestion between cooked and uncooked meals that are either intact or ground using the Burmese python and bearded dragon.
- Dr. Leslie Leinwand, Department of Molecular, Cellular, and Developmental Biology, University of Colorado
- We are collaborating with Dr. Leinwand's lab to investigate the signals and molecular mechanisms responsible for the rapid hypertrophy of the python's heart after feeding.
- Dr. Martin Grosell, Rosenstiel School of Marine and Atmospheric Science, University of Miami
- We are working with Dr. Grosell's lab to examine the postfeeding changes in gastric and intestinal metabolism and the capacity for gastric acid and intestinal base secretion of fasted and fed snakes.