The heart requires glycerol as an energy substrate through aquaporin 7, a glycerol facilitator.
OBJECTIVE
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 aquaglyceroporin family that is 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.


RESULTS
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 analysed in ex vivo beating hearts. Cardiac morphology and function in KO mice were similar to those of wild-type (WT) mice under basal conditions, although low glycerol and ATP content were 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.


CONCLUSIONS
The results indicate that AQP7 acts as a glycerol facilitator in cardiomyocytes and that glycerol is a substrate for cardiac energy production.
Hibuse
Toshiyuki
T
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2-B5 Yamada-oka, Suita, Osaka, Japan.
Maeda
Norikazu
N
Nakatsuji
Hideaki
H
Tochino
Yoshihiro
Y
Fujita
Koichi
K
Kihara
Shinji
S
Funahashi
Tohru
T
Shimomura
Iichiro
I
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D051397:Aquaglyceroporins / Q000235:genetics / Q000378:metabolism*; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000009:adverse effects; D004734:Energy Metabolism / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000473:pathology; D007545:Isoproterenol / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology
C491927:Aqp7 protein, mouse; D051397:Aquaglyceroporins; D020346:Aquaporins; D002316:Cardiotonic Agents; D005227:Fatty Acids; D000255:Adenosine Triphosphate; D005947:Glucose; D007545:Isoproterenol; D005990:Glycerol