Long-term Western diet fed apolipoprotein E-deficient rats exhibit only modest early atherosclerotic characteristics

Ida Rune; Bidda Rolin; Jens Lykkesfeldt; Dennis Sandris Nielsen; Łukasz Krych; Jenny E. Kanter; Karin E. Bornfeldt; Pernille Kihl; Karsten Buschard; Knud Josefsen; Johannes Josef Fels; Alan Mortensen; Berit Christoffersen; Rikke Kaae Kirk; Axel Kornerup Hansen

doi:10.1038/s41598-018-23835-z

Long-term Western diet fed apolipoprotein E-deficient rats exhibit only modest early atherosclerotic characteristics

Ida Rune, Bidda Rolin, Jens Lykkesfeldt, Dennis Sandris Nielsen, Łukasz Krych, Jenny E. Kanter, Karin E. Bornfeldt, Pernille Kihl, Karsten Buschard, Knud Josefsen, Johannes Josef Fels, Alan Mortensen, Berit Christoffersen, Rikke Kaae Kirk, Axel Kornerup Hansen^*

^*Corresponding author for this work

13 Citations (Scopus)

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Abstract

In the apolipoprotein E-deficient mouse, the gut microbiota has an impact on the development of atherosclerosis, but whether such correlations are also present in rats requires investigation. Therefore, we studied female SD-Apoe ^tm1sage (Apoe ^-/-) rats fed either a Western diet or a low-fat control diet with or without gluten, which is known to promote gut microbiota changes, until 20 weeks of age. We hypothesized that the manifestation of atherosclerosis would be more severe in Apoe ^-/- rats fed the Western high-fat diet, as compared with rats fed the low-fat diet, and that atherosclerosis would be accelerated by gluten. Both Western diet-feeding and gluten resulted in significant changes in gut microbiota, but the microbiota impact of gluten was transient. Compared with Apoe ^-/- rats fed a low-fat diet, Western diet-fed Apoe ^-/- rats were heavier and became glucose intolerant with increased levels of oxidative stress. They developed early fatty streak lesions in their aortic sinus, while there was no evidence of atherosclerosis in the thoracic aorta. No conclusions could be made on the impact of gluten on atherosclerosis. Although Western diet-fed Apoe ^-/- rats exhibited a more human-like LDL dominated blood lipid profile, signs of obesity, type 2 diabetes and cardiovascular disease were modest.

Original language	English
Article number	5416
Journal	Scientific Reports
Volume	8
Issue number	1
Number of pages	12
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-018-23835-z
Publication status	Published - 2018

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Long-term Western diet fed apolipoprotein E-deficient rats exhibit only modest early atherosclerotic characteristicsFinal published version, 2.75 MBLicence: CC BY

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Rune, I., Rolin, B., Lykkesfeldt, J., Nielsen, D. S., Krych, Ł., Kanter, J. E., Bornfeldt, K. E., Kihl, P., Buschard, K., Josefsen, K., Fels, J. J., Mortensen, A., Christoffersen, B., Kirk, R. K., & Hansen, A. K. (2018). Long-term Western diet fed apolipoprotein E-deficient rats exhibit only modest early atherosclerotic characteristics. Scientific Reports, 8(1), Article 5416. https://doi.org/10.1038/s41598-018-23835-z

Rune, I, Rolin, B, Lykkesfeldt, J , Nielsen, DS , Krych, Ł, Kanter, JE, Bornfeldt, KE, Kihl, P, Buschard, K, Josefsen, K, Fels, JJ, Mortensen, A, Christoffersen, B, Kirk, RK & Hansen, AK 2018, 'Long-term Western diet fed apolipoprotein E-deficient rats exhibit only modest early atherosclerotic characteristics', Scientific Reports, vol. 8, no. 1, 5416. https://doi.org/10.1038/s41598-018-23835-z

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title = "Long-term Western diet fed apolipoprotein E-deficient rats exhibit only modest early atherosclerotic characteristics",

abstract = "In the apolipoprotein E-deficient mouse, the gut microbiota has an impact on the development of atherosclerosis, but whether such correlations are also present in rats requires investigation. Therefore, we studied female SD-Apoe tm1sage (Apoe -/-) rats fed either a Western diet or a low-fat control diet with or without gluten, which is known to promote gut microbiota changes, until 20 weeks of age. We hypothesized that the manifestation of atherosclerosis would be more severe in Apoe -/- rats fed the Western high-fat diet, as compared with rats fed the low-fat diet, and that atherosclerosis would be accelerated by gluten. Both Western diet-feeding and gluten resulted in significant changes in gut microbiota, but the microbiota impact of gluten was transient. Compared with Apoe -/- rats fed a low-fat diet, Western diet-fed Apoe -/- rats were heavier and became glucose intolerant with increased levels of oxidative stress. They developed early fatty streak lesions in their aortic sinus, while there was no evidence of atherosclerosis in the thoracic aorta. No conclusions could be made on the impact of gluten on atherosclerosis. Although Western diet-fed Apoe -/- rats exhibited a more human-like LDL dominated blood lipid profile, signs of obesity, type 2 diabetes and cardiovascular disease were modest.",

author = "Ida Rune and Bidda Rolin and Jens Lykkesfeldt and Nielsen, {Dennis Sandris} and {\L}ukasz Krych and Kanter, {Jenny E.} and Bornfeldt, {Karin E.} and Pernille Kihl and Karsten Buschard and Knud Josefsen and Fels, {Johannes Josef} and Alan Mortensen and Berit Christoffersen and Kirk, {Rikke Kaae} and Hansen, {Axel Kornerup}",

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AU - Rune, Ida

AU - Rolin, Bidda

AU - Lykkesfeldt, Jens

AU - Nielsen, Dennis Sandris

AU - Krych, Łukasz

AU - Kanter, Jenny E.

AU - Bornfeldt, Karin E.

AU - Kihl, Pernille

AU - Buschard, Karsten

AU - Josefsen, Knud

AU - Fels, Johannes Josef

AU - Mortensen, Alan

AU - Christoffersen, Berit

AU - Kirk, Rikke Kaae

AU - Hansen, Axel Kornerup

PY - 2018

Y1 - 2018

N2 - In the apolipoprotein E-deficient mouse, the gut microbiota has an impact on the development of atherosclerosis, but whether such correlations are also present in rats requires investigation. Therefore, we studied female SD-Apoe tm1sage (Apoe -/-) rats fed either a Western diet or a low-fat control diet with or without gluten, which is known to promote gut microbiota changes, until 20 weeks of age. We hypothesized that the manifestation of atherosclerosis would be more severe in Apoe -/- rats fed the Western high-fat diet, as compared with rats fed the low-fat diet, and that atherosclerosis would be accelerated by gluten. Both Western diet-feeding and gluten resulted in significant changes in gut microbiota, but the microbiota impact of gluten was transient. Compared with Apoe -/- rats fed a low-fat diet, Western diet-fed Apoe -/- rats were heavier and became glucose intolerant with increased levels of oxidative stress. They developed early fatty streak lesions in their aortic sinus, while there was no evidence of atherosclerosis in the thoracic aorta. No conclusions could be made on the impact of gluten on atherosclerosis. Although Western diet-fed Apoe -/- rats exhibited a more human-like LDL dominated blood lipid profile, signs of obesity, type 2 diabetes and cardiovascular disease were modest.

AB - In the apolipoprotein E-deficient mouse, the gut microbiota has an impact on the development of atherosclerosis, but whether such correlations are also present in rats requires investigation. Therefore, we studied female SD-Apoe tm1sage (Apoe -/-) rats fed either a Western diet or a low-fat control diet with or without gluten, which is known to promote gut microbiota changes, until 20 weeks of age. We hypothesized that the manifestation of atherosclerosis would be more severe in Apoe -/- rats fed the Western high-fat diet, as compared with rats fed the low-fat diet, and that atherosclerosis would be accelerated by gluten. Both Western diet-feeding and gluten resulted in significant changes in gut microbiota, but the microbiota impact of gluten was transient. Compared with Apoe -/- rats fed a low-fat diet, Western diet-fed Apoe -/- rats were heavier and became glucose intolerant with increased levels of oxidative stress. They developed early fatty streak lesions in their aortic sinus, while there was no evidence of atherosclerosis in the thoracic aorta. No conclusions could be made on the impact of gluten on atherosclerosis. Although Western diet-fed Apoe -/- rats exhibited a more human-like LDL dominated blood lipid profile, signs of obesity, type 2 diabetes and cardiovascular disease were modest.

U2 - 10.1038/s41598-018-23835-z

DO - 10.1038/s41598-018-23835-z

M3 - Journal article

C2 - 29615808

AN - SCOPUS:85044920848

SN - 2045-2322

VL - 8

JO - Scientific Reports

JF - Scientific Reports

IS - 1

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ER -

Long-term Western diet fed apolipoprotein E-deficient rats exhibit only modest early atherosclerotic characteristics

Abstract

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