Western and heart healthy dietary patterns differentially affect the expression of genes associated with lipid metabolism, interferon signaling and inflammation in the jejunum of Ossabaw pigs

Authors: YE, SHUMAO - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MATTHAN, NIRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LAMON-FAVA, STEFANIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Solano-Aguilar, Gloria; TURNER, JERROLD - Harvard Medical School; WALKER, MAURA - Boston University Medical School; CHAI, ZHI - Pennsylvania State University; Lakshman, Sukla; Urban, Joseph; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/10/2020
Publication Date: 4/9/2021
Citation: Ye, S., Matthan, N., Lamon-Fava, S., Solano Aguilar, G., Turner, J., Walker, M.E., Chai, Z., Lakshman, S., Urban Jr, J.F., Lichtenstein, A.H. 2021. Western and heart healthy dietary patterns differentially affect the expression of genes associated with lipid metabolism, interferon signaling and inflammation in the jejunum of Ossabaw pigs. Journal of Nutritional Biochemistry. 90:108577. https://doi.org/doi: 10.1016/j.jnutbio.2020.108577.
DOI: https://doi.org/10.1016/j.jnutbio.2020.108577

Interpretive Summary: Diet quality and statin therapy are established modulators of coronary artery disease (CAD) progression, but their effect on the gastrointestinal tract (GIT) and subsequent sequelae that could affect CAD progression are relatively unexplored. To address this gap, Ossabaw pigs were randomly assigned to receive two diets with a similar caloric content but different composition. A Western-type diet (WD; high in saturated fat, refined carbohydrate, and cholesterol, and low in fiber) or a heart healthy-type diet (HHD; high in unsaturated fat, whole grains, fruits and vegetables, supplemented with fish oil, and low in cholesterol), with or without atorvastatin, for six months. At the end of the study, RNA isolated from pig jejunal mucosa was sequenced to study gene expression. A 2-factor edgeR analysis revealed that the dietary patterns affected the expression of three genes related to lipid metabolism (SCD, FADS1, and SQLE). The expression of these genes was associated with cardiometabolic risk factors and atherosclerotic lesion severity. Additional gene enrichment analysis indicated the WD, compared to the HHD, resulted in higher expression of genes related with interferon signaling and inflammation, with some of these genes being significantly associated with inflammatory markers in the serum (TNF-a and/or hsCRP), but not atherosclerotic lesion severity. Expression of genes related to jejunum permeability function were unaffected by dietary pattern. These data suggest that the effect of dietary patterns on jejunal mucosa that contribute to atherosclerotic lesion development was likely via lipid metabolism rather than inflammation.

Technical Abstract: Diet quality and statin therapy are established modulators of coronary artery disease (CAD) progression, but their effect on the gastrointestinal tract (GIT) and subsequent sequelae that could affect CAD progression are relatively unexplored. To address this gap, Ossabaw pigs were randomly assigned to receive isocaloric amounts of a Western-type diet (WD; high in saturated fat, refined carbohydrate, and cholesterol, and low in fiber) or a heart healthy-type diet (HHD; high in unsaturated fat, whole grains, fruits and vegetables, supplemented with fish oil, and low in cholesterol), with or without atorvastatin, for six months. At the end of the study, RNA sequencing was conducted in isolated pig jejunal mucosa. A 2-factor edgeR analysis revealed that the dietary patterns resulted in three differentially expressed genes related to lipid metabolism (SCD, FADS1, and SQLE). The expression of these genes was associated with cardiometabolic risk factors and atherosclerotic lesion severity. Subsequent gene enrichment analysis indicated the WD, compared to the HHD, resulted in higher interferon signaling and inflammation, with some of these genes being significantly associated with serum TNF-a and/or hsCRP concentrations, but not atherosclerotic lesion severity. No significant effect of atorvastatin therapy on gene expression, nor diet x statin interactions, were identified. Expression of genes related to jejunum permeability were unaffected by dietary pattern or atorvastatin therapy. These data suggest that the effect of dietary patterns on jejunal mucosa that contribute to atherosclerotic lesion development was likely via lipid metabolism rather than inflammation.