Long-term Western diet fed
apolipoprotein E-defcient
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 Christofersen, Rikke Kaae Kirk & Axel Kornerup Hansen
Abstract
In the apolipoprotein E–defcient 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-Apoetm1sage (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 signifcant changes in gut
microbiota, but the microbiota impact of gluten was transient. Compared with Apoe−/− rats fed a lowfat
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 profle, signs of obesity, type 2 diabetes and cardiovascular disease were modest.
Scientific Reports (2018) 8:5416 DOI:10.1038/s41598-018-23835-z