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  VEGF and GLUT1 are highly heritable, inversely correlated and affected by dietary fat intake: Consequences for cognitive function in humans

Schüler, R., Seebeck, N., Osterhoff, M. A., Witte, V., Flöel, A., Busjahn, A., et al. (2018). VEGF and GLUT1 are highly heritable, inversely correlated and affected by dietary fat intake: Consequences for cognitive function in humans. Molecular Metabolism, 11, 129-136. doi:10.1016/j.molmet.2018.02.004.

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Schueler_Seebeck_2017.pdf (Publisher version), 839KB
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 Creators:
Schüler, Rita1, 2, Author
Seebeck, Nicole1, Author
Osterhoff, Martin A.1, 2, 3, Author
Witte, Veronica4, 5, 6, Author           
Flöel, Agnes4, 5, 7, Author
Busjahn, Andreas8, Author
Jais, Alexander9, 10, 11, Author
Brüning, Jens C.2, 9, 10, 11, Author
Frahnow, Turid1, Author
Kabisch, Stefan1, 2, 3, Author
Pivovarova, Olga1, 2, 3, Author
Hornemann, Silke1, Author
Kruse, Michael1, 3, Author
Pfeiffer, Andreas F. H.1, 2, 3, Author
Affiliations:
1Department of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany, ou_persistent22              
2German Center for Diabetes Research, Neuherberg, Germany, ou_persistent22              
3Clinic of Endocrinology, Diabetes and Nutrition, Charité University Medicine Berlin, Germany, ou_persistent22              
4Department of Neurology, Charité University Medicine Berlin, Germany, ou_persistent22              
5NeuroCure Cluster of Excellence, Charité University Medicine Berlin, Germany, ou_persistent22              
6Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
7Department of Neurology, Ernst Moritz Arndt University of Greifswald, Germany, ou_persistent22              
8HealthTwiSt GmbH, Berlin, Germany, ou_persistent22              
9Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany, ou_persistent22              
10Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Germany, ou_persistent22              
11Center of Molecular Medicine Cologne (CMMC), University of Cologne, Germany, ou_persistent22              

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Free keywords: VEGF; GLUT1; High fat diet; Cognition
 Abstract: Objective Reduction of brain glucose transporter GLUT1 results in severe neurological dysfunction. VEGF is required to restore and maintain brain glucose uptake across the blood brain barrier via GLUT1, which was shown to be acutely diminished in response to a high fat diet (HFD) in mice. The genetic and HFD-related regulation and association of VEGF and GLUT1 (SLC2A1) in humans was investigated in the NUtriGenomic Analysis in Twins (NUGAT) study. Methods 92 healthy and non-obese twins were standardized to a high-carbohydrate low-fat diet for 6 weeks before switched to a 6-week HFD under isocaloric conditions. Three clinical investigation days were conducted: after 6 weeks of low-fat diet and after 1 and 6 weeks of HFD. Serum VEGF and other cytokine levels were measured using ELISA. Gene expression in subcutaneous adipose tissue was assessed by quantitative Real-Time PCR. Genotyping was performed using microarray. The Auditory Verbal Learning Task was conducted to measure cognitive performance. Results In this human study, we showed that the environmental regulation of SLC2A1 expression and serum VEGF by HFD was inversely correlated and both factors showed strong heritability (>90%). In response to the HFD containing 45% fat, serum VEGF levels increased (P = 0.002) while SLC2A1 mRNA expression in adipose tissue decreased (P = 0.001). Higher BMI was additionally associated with lower SLC2A1 expression. AA-genotypes of the rs9472159 polymorphism, which explained ∼39% of the variation in circulating VEGF concentrations, showed significantly reduced serum VEGF levels (P = 6.4 × 10−11) but higher SLC2A1 expression (P = 0.009) in adipose tissue compared to CC/CA-genotypes after 6 weeks of HFD. Memory performance in AA-genotypes declined in response to the HFD compared to CC- and CA-genotypes. Conclusions The results provide evidence to suggest the translatability of the dietary regulation of VEGF and GLUT1 from mouse models to humans. Our data demonstrate that HFD induces a genetically determined and correlated decrease of GLUT1 and increase of VEGF which may affect memory performance.

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Language(s): eng - English
 Dates: 2018-02-022017-12-192018-02-062018-02-122018-05
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.molmet.2018.02.004
PMID: 29506909
PMC: PMC6001408
Other: Epub 2018
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Project name : -
Grant ID : 0315424
Funding program : -
Funding organization : German Federal Ministry of Education and Research (BMBF)

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Title: Molecular Metabolism
Source Genre: Journal
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Publ. Info: Amsterdam, Netherlands : Elsevier B.V.
Pages: - Volume / Issue: 11 Sequence Number: - Start / End Page: 129 - 136 Identifier: ISSN: 2212-8778
CoNE: https://pure.mpg.de/cone/journals/resource/2212-8778