(P10-012-23) Impact of Various High Fat Diets on Intestinal Gene Expression in Mouse

Objectives: The objective of the study was to compare the effect of three isocaloric high fat diets (HFDs) with varying amounts of the polyunsaturated fatty acid (PUFA), linoleic acid (LA), on gene expression in four functionally distinct segments of the mouse intestinal tract: the duodenum, jejunum, terminal ileum, and proximal colon.

Methods: Male C57BL/6N mice were weaned at three weeks of age and assigned randomly to one of the four diets used in the study –low fat Vivarium (VIV) chow, 40% kcal fat coconut oil (CO), 40% kcal CO plus soybean oil (CO+SO), 40% kcal CO plus genetically modified soybean oil Plenish which has low LA (CO+PL). Individual mouse weights were recorded once a week while food was changed twice a week. Mice were kept on the assigned diets for up to 24 weeks. At the end of the study, animals were euthanized, and intestinal tissue was excised immediately and put in RNALater. RNA extracts from three (for Viv) or four (for the HFDs) biological replicates for each diet were sequenced on an Illumina HiSeq 2000. Reads were aligned to the mouse reference genome (mm10) with STAR v2.5.0a using default parameters and analyzed using standard bioinformatic techniques.

Results: We found dysregulation of more than 400 genes involved in epithelial barrier function, inflammatory bowel disease (IBD), colon cancer, microbiome, xenobiotic, and drug metabolism in different tissues with the different diets. A network analysis showed that many genes involved in the immune system are affected by different diets and revealed a potential impact of HFDs on gut health related to bacterial and viral infections, including SARS-CoV-2.

Conclusions: Our results reveal that gene expression in various segments of the intestines varies considerably and that isocaloric high fat diets with varying fatty acid composition can differentially impact this pattern. Furthermore, the changes in intestinal gene expression correlate with inflammatory and metabolic conditions, underscoring the importance of diet not just for intestinal health but for the well-being of the entire organism.

Funding Sources: National Institutes of Health; National Institutes of Environmental Health Science; Crohn’s & Colitis Foundation Career Development Award