Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: a PET study with [(11)C]acetate in humans

Peter Iversen; Kim Mouridsen; Mikkel B Hansen; Svend B Jensen; Michael Sørensen; Lasse Kristoffer Bak; Helle S Waagepetersen; Arne Schousboe; Peter Ott; Hendrik Vilstrup; Susanne Keiding; Albert Gjedde

doi:10.3389/fnins.2014.00353

Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: a PET study with [(11)C]acetate in humans

Peter Iversen, Kim Mouridsen, Mikkel B Hansen, Svend B Jensen, Michael Sørensen, Lasse Kristoffer Bak, Helle S Waagepetersen, Arne Schousboe, Peter Ott, Hendrik Vilstrup, Susanne Keiding, Albert Gjedde

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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 [¹¹C]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 [¹¹C]acetate. No significant differences of the rate constant of oxidation of [¹¹C]acetate (k₃) were found among the three groups of subjects. The net metabolic clearance of [¹¹C]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 [¹¹C]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.

Originalsprog	Engelsk
Tidsskrift	Frontiers in Neuroscience
Vol/bind	8
Sider (fra-til)	353
ISSN	1662-4548
DOI	https://doi.org/10.3389/fnins.2014.00353
Status	Udgivet - 2014

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10.3389/fnins.2014.00353Licens: CC BY

fnins-08-00353Forlagets udgivne version, 1,92 MBLicens: CC BY

Citationsformater

Iversen, P., Mouridsen, K., Hansen, M. B., Jensen, S. B., Sørensen, M., Bak, L. K., Waagepetersen, H. S., Schousboe, A., Ott, P., Vilstrup, H., Keiding, S., & Gjedde, A. (2014). Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: a PET study with [(11)C]acetate in humans. Frontiers in Neuroscience, 8, 353. https://doi.org/10.3389/fnins.2014.00353

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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 [11C]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 [11C]acetate. No significant differences of the rate constant of oxidation of [11C]acetate (k3) were found among the three groups of subjects. The net metabolic clearance of [11C]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 [11C]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.",

author = "Peter Iversen and Kim Mouridsen and Hansen, {Mikkel B} and Jensen, {Svend B} and Michael S{\o}rensen and Bak, {Lasse Kristoffer} and Waagepetersen, {Helle S} and Arne Schousboe and Peter Ott and Hendrik Vilstrup and Susanne Keiding and Albert Gjedde",

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doi = "10.3389/fnins.2014.00353",

language = "English",

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pages = "353",

journal = "Frontiers in Neuroscience",

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T1 - Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy

T2 - a PET study with [(11)C]acetate in humans

AU - Iversen, Peter

AU - Mouridsen, Kim

AU - Hansen, Mikkel B

AU - Jensen, Svend B

AU - Sørensen, Michael

AU - Bak, Lasse Kristoffer

AU - Waagepetersen, Helle S

AU - Schousboe, Arne

AU - Ott, Peter

AU - Vilstrup, Hendrik

AU - Keiding, Susanne

AU - Gjedde, Albert

PY - 2014

Y1 - 2014

N2 - 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 [11C]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 [11C]acetate. No significant differences of the rate constant of oxidation of [11C]acetate (k3) were found among the three groups of subjects. The net metabolic clearance of [11C]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 [11C]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.

AB - 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 [11C]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 [11C]acetate. No significant differences of the rate constant of oxidation of [11C]acetate (k3) were found among the three groups of subjects. The net metabolic clearance of [11C]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 [11C]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.

U2 - 10.3389/fnins.2014.00353

DO - 10.3389/fnins.2014.00353

M3 - Journal article

C2 - 25404890

SN - 1662-4548

VL - 8

SP - 353

JO - Frontiers in Neuroscience

JF - Frontiers in Neuroscience

ER -

Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: a PET study with [(11)C]acetate in humans

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