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27-Hydroxycholester...
27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation
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- Ismail, MA (författare)
- Karolinska Institutet
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Mateos, L (författare)
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- Maioli, S (författare)
- Karolinska Institutet
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visa fler...
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Merino-Serrais, P (författare)
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Ali, Z (författare)
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Lodeiro, M (författare)
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- Westman, E (författare)
- Karolinska Institutet
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Leitersdorf, E (författare)
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- Gulyas, B (författare)
- Karolinska Institutet
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Olof-Wahlund, L (författare)
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- Winblad, B (författare)
- Karolinska Institutet
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Savitcheva, I (författare)
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- Bjorkhem, I (författare)
- Karolinska Institutet
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- Cedazo-Minguez, A (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2017-02-17
- 2017
- Engelska.
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 214:3, s. 699-717
- Relaterad länk:
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https://rupress.org/...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced 18F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)–mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N). These effects were mediated by liver X receptors. Our results reveal a molecular link between cholesterol, brain glucose, and the brain renin-angiotensin system, all of which are affected in some neurodegenerative diseases. Thus, reducing 27-OH levels or inhibiting AP-N maybe a useful strategy in the prevention of the altered glucose metabolism and memory decline in these disorders.
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- art (ämneskategori)
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Ismail, MA
-
Mateos, L
-
Maioli, S
-
Merino-Serrais, ...
-
Ali, Z
-
Lodeiro, M
-
visa fler...
-
Westman, E
-
Leitersdorf, E
-
Gulyas, B
-
Olof-Wahlund, L
-
Winblad, B
-
Savitcheva, I
-
Bjorkhem, I
-
Cedazo-Minguez, ...
-
visa färre...
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The Journal of e ...
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Karolinska Institutet