Acute high-fat high-sugar diet rapidly increases blood-brain barrier permeability in mice

The blood-brain barrier (BBB) maintains brain homeostasis by protecting the brain from pathological stimuli and controlling the entry of physiological substances from the periphery. Consequently, alterations in BBB permeability may pose a threat to brain health. Long-term consumption of a high-fat h...

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Main Authors: Este Leidmaa, Andreas Zimmer, Valentin Stein, Anne-Kathrin Gellner
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:The Journal of Nutrition, Health and Aging
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Online Access:http://www.sciencedirect.com/science/article/pii/S1279770725000983
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author Este Leidmaa
Andreas Zimmer
Valentin Stein
Anne-Kathrin Gellner
author_facet Este Leidmaa
Andreas Zimmer
Valentin Stein
Anne-Kathrin Gellner
author_sort Este Leidmaa
collection DOAJ
description The blood-brain barrier (BBB) maintains brain homeostasis by protecting the brain from pathological stimuli and controlling the entry of physiological substances from the periphery. Consequently, alterations in BBB permeability may pose a threat to brain health. Long-term consumption of a high-fat high-sugar/Western diet (HFD) is known to induce BBB dysfunction. However, nothing is known about the immediate effects of acute HFD consumption on the BBB. Using spectrophotometry and in vivo 2-photon microscopy in mice, we demonstrate region-specific BBB leakage already after 1 h of HFD for low- and high-molecular-weight tracers. Acute HFD also significantly increased BBB permeability to the anticancer drug doxorubicin. These previously unknown effects of acute HFD in mice may have far-reaching implications for the clinical use of drugs depending on the dietary habits of the patient, and might inform future studies on drug transport to the brain.
format Article
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institution OA Journals
issn 1760-4788
language English
publishDate 2025-07-01
publisher Elsevier
record_format Article
series The Journal of Nutrition, Health and Aging
spelling doaj-art-7ad0637d76d8466bb90fa5ae920675332025-08-20T02:36:23ZengElsevierThe Journal of Nutrition, Health and Aging1760-47882025-07-0129710057410.1016/j.jnha.2025.100574Acute high-fat high-sugar diet rapidly increases blood-brain barrier permeability in miceEste Leidmaa0Andreas Zimmer1Valentin Stein2Anne-Kathrin Gellner3Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Department of Physiology, Medical Faculty, University of Tartu, 19 Ravila Street, Tartu 50411, Estonia; Corresponding author at: Department of Physiology, Medical Faculty, University of Tartu, 19 Ravila Street, Tartu 50411, Estonia.Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, GermanyInstitute of Physiology II, Medical Faculty, University of Bonn, Nussallee 11, 53115 Bonn, GermanyInstitute of Physiology II, Medical Faculty, University of Bonn, Nussallee 11, 53115 Bonn, Germany; Department of Psychiatry and Psychotherapy, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Corresponding author at: Institute of Physiology II, Medical Faculty, University of Bonn, Nussallee 11, Bonn 53115, Germany.The blood-brain barrier (BBB) maintains brain homeostasis by protecting the brain from pathological stimuli and controlling the entry of physiological substances from the periphery. Consequently, alterations in BBB permeability may pose a threat to brain health. Long-term consumption of a high-fat high-sugar/Western diet (HFD) is known to induce BBB dysfunction. However, nothing is known about the immediate effects of acute HFD consumption on the BBB. Using spectrophotometry and in vivo 2-photon microscopy in mice, we demonstrate region-specific BBB leakage already after 1 h of HFD for low- and high-molecular-weight tracers. Acute HFD also significantly increased BBB permeability to the anticancer drug doxorubicin. These previously unknown effects of acute HFD in mice may have far-reaching implications for the clinical use of drugs depending on the dietary habits of the patient, and might inform future studies on drug transport to the brain.http://www.sciencedirect.com/science/article/pii/S1279770725000983Western dietPalatable foodVascular leakageBBB integrityDrug delivery
spellingShingle Este Leidmaa
Andreas Zimmer
Valentin Stein
Anne-Kathrin Gellner
Acute high-fat high-sugar diet rapidly increases blood-brain barrier permeability in mice
The Journal of Nutrition, Health and Aging
Western diet
Palatable food
Vascular leakage
BBB integrity
Drug delivery
title Acute high-fat high-sugar diet rapidly increases blood-brain barrier permeability in mice
title_full Acute high-fat high-sugar diet rapidly increases blood-brain barrier permeability in mice
title_fullStr Acute high-fat high-sugar diet rapidly increases blood-brain barrier permeability in mice
title_full_unstemmed Acute high-fat high-sugar diet rapidly increases blood-brain barrier permeability in mice
title_short Acute high-fat high-sugar diet rapidly increases blood-brain barrier permeability in mice
title_sort acute high fat high sugar diet rapidly increases blood brain barrier permeability in mice
topic Western diet
Palatable food
Vascular leakage
BBB integrity
Drug delivery
url http://www.sciencedirect.com/science/article/pii/S1279770725000983
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AT andreaszimmer acutehighfathighsugardietrapidlyincreasesbloodbrainbarrierpermeabilityinmice
AT valentinstein acutehighfathighsugardietrapidlyincreasesbloodbrainbarrierpermeabilityinmice
AT annekathringellner acutehighfathighsugardietrapidlyincreasesbloodbrainbarrierpermeabilityinmice