Cardiovascular Research Advance Access [Accepted Manuscript] published online on March 18, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp095
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The heart requires glycerol as an energy substrate through aquaporin 7, a glycerol facilitator
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2-B5 Yamada-oka, Suita, Osaka 565-0871, Japan
* Corresponding author: Norikazu Maeda, MD, PhD, Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2, B5, Yamada-oka, Suita, Osaka 565-0871, Japan, Telephone; +81-6-6879-3732, Fax; +81-6-6879-3739, E-mail; nmaeda{at}imed2.med.osaka-u.ac.jp
Aims: Cardiomyocytes require fatty acids and glucose for energy production. However, other nutrients and substrates that may serve as possible candidates for a cardiac energy source have not been fully studied. Several reports showed that a moderate expression of aquaporin 7 (AQP7), a member of the aquaglyceroporins family that are permeated by glycerol and water, is observed in heart tissue. However, the functional role of cardiac AQP7 is not clear. The aim of this study was to investigate the significance of glycerol as a cardiac energy substrate and to clarify the role of cardiac AQP7.
Methods: Heart function and morphology were examined in AQP7-knockout (KO) mice under basal conditions and during pressure overload [isoproterenol infusion and transverse aortic constriction (TAC)]. Glycerol uptake and glycerol-dependent ATP production were measured in AQP7-knockdown cardiac cells. Cardiac glycerol consumption was analyzed in ex vivo beating hearts.
Results: Cardiac morphology and function in KO mice were similar to those of wild-type (WT) mice under basal conditions, while low glycerol and ATP content was noted in hearts of KO mice. In H9c2 cardiomyotubes, knockdown of AQP7 was associated with a significant reduction of glycerol uptake. The ex vivo heart study demonstrated that cardiac glycerol consumption levels in KO mice were significantly lower than those of WT mice. Furthermore, isoproterenol challenge induced severe left ventricular hypertrophy in KO mice, and TAC resulted in a higher mortality rate in KO mice than in WT mice.
Conclusion: The results indicate that AQP7 acts as a glycerol facilitator in cardiomyocytes and that glycerol is a substrate for cardiac energy production.
KEYWORDS aquaporin; glycerol; heart; energy metabolism
Time for primary review: 21 Days
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Cardiovasc Res 2009 83: 3-4.
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  M. Gladka, H. el Azzouzi, L. J. De Windt, and P. A. da Costa Martins Aquaporin 7: the glycerol aquaeductus in the heart Cardiovasc Res, July 1, 2009; 83(1): 3 - 4. [Full Text] [PDF]
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