Fatty Acids Identified in the Burmese Python Promote Beneficial Cardiac Growth

Abstract

Burmese pythons display a dramatic increase in heart mass after a large meal. We investigated the molecular mechanisms of this physiological heart growth, with the goal of applying this knowledge to the mammalian heart. We found that heart growth in pythons is characterized by myocyte hypertrophy in the absence of cell proliferation and by activation of PI3K/Akt/mTor signaling pathways. Despite high levels of circulating lipids, the postprandial python heart does not accumulate triglycerides or fatty acids. Instead, there is robust activation of pathways of fatty acid transport and oxidation combined with increased expression and activity of the cardioprotective enzyme, superoxide dismutase. Finally, we identified a combination of fatty acids in python plasma that promotes physiological heart growth when injected into either pythons or mice.

Improved cardiac filling facilitates the postprandial elevation of stroke volume inPython regius

“…This is consistent with the fact that reptiles are endowed with the capacity for very high ejection fractions (Burggren et al, 2013), making it unlikely that increased contractility and the associated reduction of end-systolic volume could contribute significantly to the doubling of V S during digestion. We did find an increase in cytochrome oxidase activity in the cardiac muscle, consistent with the increased gene expression previously reported (Riquelme et al, 2011), identifying an increased oxidative capacity. As contractility is unchanged, this increased capacity probably supports the 50% increase in heart rate after feeding.…”

Reduction of blood oxygen levels enhances postprandial cardiac hypertrophy in Burmese python (Python molurus)

“…Andersen et al, 2005;Riquelme et al, 2011), and support the proposal that postprandial cardiac hypertrophy is a facultative response in pythons (Jensen et al, 2011;Hansen et al, 2013;Enok et al, 2013). In contrast, postprandial enlargement of the small intestine, liver and kidneys seems consistent amongst studies (Secor and Diamond, 1995;Secor and Diamond, 1998;Starck and Beese, 2001;Ott and Secor, 2007;Cox and Secor, 2008;Jensen et al, 2011;Hansen et al, 2013;Enok et al, 2013).…”

“…These growth factors are then involved in paracrine and/or autocrine activation of the phosphatidylinositol 3′-kinase (PI3K)-Akt-mTOR pathway, which ultimately leads to synthesis of contractile elements (Dorn and Force, 2005;Shiojima and Walsh, 2006;Dorn, 2007;Hill and Olson, 2008). AMPK, Akt, GSK3β and mTOR, all signaling molecules in mammalian physiologic hypertrophy pathways mediated by mechanical stress, are known to be active in the python model (Riquelme et al, 2011). This suggests that the cardiac hypertrophy in pythons occurs in response to elevated mechanical stress on ventricular myocytes.…”

“…This hemodynamic response is mitigated largely by a reduction in cholinergic tone and positive chronotropic effects of non-adrenergic, non-cholinergic (NANC) factors, including an increased histaminergic tone (Wang et al, 2001a;Skovgaard et al, 2009;Enok et al, 2012;Enok et al, 2013;Burggren et al, 2014). The rise in stroke volume has been linked with a 40% increase in ventricular mass within 48 h of eating (Andersen et al, 2005) that Riquelme et al described as being 'physiological' in nature and triggered by humoral factors, including increased levels of circulating free fatty acids (Riquelme et al, 2011). The universality and stimulus of the postprandial cardiac hypertrophy, however, remain unclear as Jensen et al found no postprandial cardiac hypertrophy in Burmese or Ball pythons (Python regius) under a similar experimental protocol (Jensen et al, 2011).…”

Applicability of Yellow Pigmented Microbe obtained from Indian Rock Python Fecal Sample as Bio-Ink

“…The possibility of finding the same in fat utilizing niche prompted to target fecal sample of python, the model organism for cholesterol metabolic study (Riquelme, 2011). Series of studies involved in screening pigmented microbes from various environmental sources have been reported, but no attempt for the same with regards to python fecal sample has been ventured.…”