It's a pretty rare paper that includes providing transfusions to Burmese pythons. It's rarer still for that sort of paper to have potential implications for human health. But a paper that fits that description will be appearing in today's edition of Science. Pythons, you see, can grow their heart mass by up to 40 percent within three days of a large meal, without any of the problems that major metabolic changes often cause in humans. Researchers have now figured out the signal that drives this rapid expansion, and shown that it has similar effects in mice.
The process that allows the python's heart to expand is called hypertrophy. Instead of expanding the cells present in the heart, each of the heart's muscle cells grows in size, adding more of the structures that allow its steady contractions. But not all hypertrophy is good; in many cardiac diseases, these same cells expand in size, but appear to revert to an earlier stage of development, showing the sort of gene expression and behavior typical of the fetal heart. This ultimately weakens the organ; the authors of the new paper describe it as "a leading predictor of mortality."
Humans and other mammals can undergo the good type of hypertrophy when following an exercise regime or during pregnancy. But it typically takes weeks, and the growth is relatively modest (less than half that of the python).
Pythons don't grow their heart in response to exercise. Instead, it's part of a suite of adaptations to a lifestyle that features long periods of inactivity, interspersed with infrequent, large meals. When the meal hits, the whole python's body responds, with other organs besides the heart growing to cope with the metabolic strain. It's estimated that, following a meal, the snake's metabolism will increase by a factor of over 40.
Along with that increase comes a healthy dose of fat. In the snakes the researchers looked at, blood triglycerides went up by a factor of 52, and some types of fatty acids shot up three-fold. In most animals, this would be enough to cause fat deposits to form in a variety of tissues, including the heart. But this doesn't happen in the python.
The authors confirmed that the python's heart expands without adding new cells, and that the expansion is accompanied by a suite of changes that expand its metabolic capacity, boost protein synthesis, and clear out free oxygen radicals, products of metabolism that can damage the tissue.
To test whether this was unique to snakes, the authors isolated some blood plasma from the pythons and added it to cultured heart cells from rats. Those cells responded in the same way that the python's cells did, and followed a similar profile—the rat cells showed the biggest boost in growth from plasma obtained from snakes that were experiencing the highest rate of heart expansion.
Reasoning there was some factor in the blood that provided this boost, the authors tried to destroy it by treating it with an enzyme that chops up proteins. That didn't work. So they heat-treated the plasma. That didn't work, either. So, the authors began to suspect the fatty acids that they had observed earlier. Although the same specific fatty acids were present, the ratios between them changed after the animals had a meal.
So, they set up a precise mixture of three (myristic, palmitic, and palmitoleic acids) and tested that by transfusing it into a fasting python. The snakes responded as if they had just eaten a meal. The mixture also worked on cultured rat cells. And, when transfused into mice, it provided a significant boost to heart mass. As in snakes, the expansion of the mouse heart occurred largely through the growth in cardiac muscle cells.
Although the increase in heart mass seen in the mice isn't as large as the python experiences, it's still over 10 percent, about what you might expect from an exercise program. But the authors aren't suggesting they've found a way for you to stay out of the gym. Instead, they focus on the idea that this mix of fatty acids might alter the harmful form of hypertrophy that occurs in many cardiac diseases, diverting it into something a bit more healthy. There are plenty of mouse models of hypertrophic cardiomyopathy out there, so chances are good that these experiments are already underway.