title: The heart requires glycerol as an energy substrate through aquaporin 7, a glycerol facilitator.
abstract: 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.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2-B5 Yamada-oka, Suita, Osaka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hibuse
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakatsuji
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tochino
authors.forename: Koichi
authors.initials: K
authors.lastname: Fujita
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: 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
chemical_list: C491927:Aqp7 protein, mouse; D051397:Aquaglyceroporins; D020346:Aquaporins; D002316:Cardiotonic Agents; D005227:Fatty Acids; D000255:Adenosine Triphosphate; D005947:Glucose; D007545:Isoproterenol; D005990:Glycerol