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Science 334 (6055): 528-531

Copyright © 2011 by the American Association for the Advancement of Science

Fatty Acids Identified in the Burmese Python Promote Beneficial Cardiac Growth

Cecilia A. Riquelme1, Jason A. Magida1, Brooke C. Harrison1, Christopher E. Wall1, Thomas G. Marr2, Stephen M. Secor3, and Leslie A. Leinwand1,*

1 Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
2 Hiberna Corporation, Boulder, CO 80302, USA.
3 Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USA.

Figure 1
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Fig. 1. Postprandial cardiac growth in the python is characterized by cellular hypertrophy and activation of protein synthesis pathways. (A) Masson trichrome–stained python hearts depicting pronounced postprandial cardiac hypertrophy. Scale bar, 2 mm. (B) BrdU staining of 0- and 1-dpf python hearts shows no evidence of postprandial cellular proliferation. Python small intestine is included as a positive control (brown nuclear staining). Scale bar, 50 μm. (C) The number of nuclei per field is reduced post-feeding. Error bars represent ±SE; n = 4 per condition; *P < 0.05 versus 0 dpf. (D) Immunoblot analysis reveals increased phosphorylation of AMPK, Akt, GSK3β, and mTOR in the postprandial python heart.


Figure 2
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Fig. 2. The postprandial python heart has increased expression of fatty acid transport, handling, and oxidation genes along with enhanced free radical–scavenging capacity. (A) Plasma non-esterified fatty acid (NEFA) and triacylglyceride (TAG) concentrations are significantly increased after feeding. (B) Oil Red O staining reveals no cardiac accumulation of neutral lipids at 3 dpf. Mitochondrial staining is increased in the post-fed python heart as determined by cytochrome c oxidase II (COX2) immunostaining and NADH-tetrazolium reductase (NADH-TR) histochemistry. Scale bar, 50 μm. (C) Increased mRNA expression of CD36, mFABP, CPT1B, and the β-oxidation proteins MCAD, ECHD, and ACAA2 is observed after feeding. (D) The mRNA expression and activity of mitochondrial SOD2 is increased post-feeding. Error bars represent ±SE; n = 4 per condition; *P < 0.05 versus 0 dpf.


Figure 3
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Fig. 3. Postprandial python plasma induces cardiomyocyte growth in vitro. (A) Fed python plasma induces cellular hypertrophy in neonatal rat cardiac myocytes (NRVMs). NP, no plasma; PE, phenylephrine (included as a positive control). The light microscope images show NRVMs stained for α-actinin (green) and nuclei (blue); scale bar, 10 μm. (B) Python plasma does not induce the mRNA expression of known cardiac stress markers in NRVMs. ANF, atrial natriuretic factor; MYH6, α–myosin heavy chain; MYH7, β–myosin heavy chain; ACTA1, α–skeletal actin. (C) Pathological NFAT signaling is repressed by python plasma. (D) Supplementing fasted python plasma with C14:0, C16:0, and C16:1 (0 dpf + FAs) results in cellular hypertrophy comparable to that seen with 1-dpf plasma. Error bars represent ±SE; n = 3 per condition; *P < 0.05 versus 0 dpf [(A) and (D)]; *P < 0.05 versus PE (B); *P < 0.05 versus NP (C).


Figure 4
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Fig. 4. Postprandial python plasma fatty acids induce cardiac growth in vivo. (A) Infusing fasted pythons with fed plasma or C14:0, C16:0, and C16:1 (FAs) results in increased heart mass (heart weight/body weight) comparable to that seen with ingestion of a rodent meal (3 dpf). Bovine serum albumin (BSA) was used to solubilize FAs. (B) Seven-day infusion of FAs in mice results in increased left ventricular mass (left ventricular mass/tibia length) and increased relative myocyte cross-sectional area. (C) FA infusion in mice results in a modest but statistically significant increase in MYH6 mRNA expression with no change in MYH7 or atrial natriuretic factor (ANF). Error bars represent ±SE; n = 3 (A) or 6 [(B) and (C)] per condition; *P < 0.05 versus fasted python (A); *P < 0.05 versus BSA [(B) and (C)].


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