title: Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: a PET study with [(11)C]acetate in humans.
abstract: In patients with impaired liver function and hepatic encephalopathy (HE), consistent elevations of blood ammonia concentration suggest a crucial role in the pathogenesis of HE. Ammonia and acetate are metabolized in brain both primarily in astrocytes. Here, we used dynamic [(11)C]acetate PET of the brain to measure the contribution of astrocytes to the previously observed reduction of brain oxidative metabolism in patients with liver cirrhosis and HE, compared to patients with cirrhosis without HE, and to healthy subjects. We used a new kinetic model to estimate uptake from blood to astrocytes and astrocyte metabolism of [(11)C]acetate. No significant differences of the rate constant of oxidation of [(11)C]acetate (k 3) were found among the three groups of subjects. The net metabolic clearance of [(11)C]acetate from blood was lower in the group of patients with cirrhosis and HE than in the group of healthy subjects (P < 0.05), which we interpret to be an effect of reduced cerebral blood flow rather than a reflection of low [(11)C]acetate metabolism. We conclude that the characteristic decline of whole-brain oxidative metabolism in patients with cirrhosis with HE is not due to malfunction of oxidative metabolism in astrocytes. Thus, the observed decline of brain oxidative metabolism implicates changes of neurons and their energy turnover in patients with HE.
authors.affiliation: Department of Nuclear Medicine and PET Centre, Aarhus University Hospital Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Iversen
authors.affiliation: Center of Functionally Integrative Neuroscience, Aarhus University Aarhus, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Mouridsen
authors.affiliation: Center of Functionally Integrative Neuroscience, Aarhus University Aarhus, Denmark.
authors.forename: Mikkel B
authors.initials: MB
authors.lastname: Hansen
authors.affiliation: Department of Nuclear Medicine, Aalborg University Hospital Aalborg, Denmark ; Department of Chemistry and Biochemistry, Aalborg University Aalborg, Denmark.
authors.forename: Svend B
authors.initials: SB
authors.lastname: Jensen
authors.affiliation: Department of Nuclear Medicine and PET Centre, Aarhus University Hospital Aarhus, Denmark ; Department of Hepatology and Gastroenterology, Aarhus University Hospital Aarhus, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Sørensen
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen, Denmark.
authors.forename: Lasse K
authors.initials: LK
authors.lastname: Bak
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen, Denmark.
authors.forename: Helle S
authors.initials: HS
authors.lastname: Waagepetersen
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen, Denmark.
authors.forename: Arne
authors.initials: A
authors.lastname: Schousboe
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Ott
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital Aarhus, Denmark.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Vilstrup
authors.affiliation: Department of Nuclear Medicine and PET Centre, Aarhus University Hospital Aarhus, Denmark ; Department of Hepatology and Gastroenterology, Aarhus University Hospital Aarhus, Denmark ; Brain Research and Integrative Neuroscience Laboratory, Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Keiding
authors.affiliation: Department of Nuclear Medicine and PET Centre, Aarhus University Hospital Aarhus, Denmark ; Center of Functionally Integrative Neuroscience, Aarhus University Aarhus, Denmark ; Brain Research and Integrative Neuroscience Laboratory, Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen, Denmark.
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
keywords: astrocytes; brain energy metabolism; kinetic modeling; mitochondria; positron emission tomography