Colon transcriptome is modified by a dietary pattern/atorvastatin interaction in the Ossabaw pig.

Publisher: Elsevier Science Country of Publication: United States NLM ID: 9010081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4847 (Electronic) Linking ISSN: 09552863 NLM ISO Abbreviation: J Nutr Biochem Subsets: MEDLINE

Publication: <1996->: New York, NY : Elsevier Science
Original Publication: Stoneham, MA, USA : Butterworths, c1990-

Atorvastatin/*pharmacology ; Colon/*metabolism ; Coronary Artery Disease/*drug therapy ; Diet/*methods ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology ; Transcriptome/*drug effects; Animals ; Atherosclerosis/genetics ; Atherosclerosis/metabolism ; Cholesterol, Dietary/pharmacology ; Colon/drug effects ; Coronary Artery Disease/genetics ; Coronary Artery Disease/metabolism ; Diet, Healthy/methods ; Diet, High-Fat/methods ; Diet, Western ; Dietary Fats/pharmacology ; Feeding Behavior ; Female ; Gene Expression ; Humans ; Male ; Swine

Optimizing diet quality in conjunction with statin therapy is currently the most common approach for coronary artery disease (CAD) risk management. Although effects on the cardiovascular system have been extensively investigated, little is known about the effect of these interventions in the colon and subsequent associations with CAD progression. To address this gap, Ossabaw pigs were randomly allocated to receive, for a six-month period, isocaloric amounts of either a heart healthy-type diet (HHD; high in unrefined carbohydrate, unsaturated fat, fiber, supplemented with fish oil, and low in cholesterol) or a Western-type diet (WD; high in refined carbohydrate, saturated fat and cholesterol, and low in fiber), without or with atorvastatin therapy. At the end of the intervention period, colon samples were harvested, mucosa fraction isolated, and RNA sequenced. Gene differential expression and enrichment analyses indicated that dietary patterns and atorvastatin therapy differentially altered gene expression, with diet-statin interactions. Atorvastatin had a more profound effect on differential gene expression than diet. In pigs not receiving atorvastatin, the WD upregulated "LXR/RXR Activation" pathway compared to pigs fed the HHD. Enrichment analysis indicated that atorvastatin therapy lowered inflammatory status in the HHD-fed pigs, whereas it induced a colitis-like gene expression phenotype in the WD-fed pigs. No significant association was identified between gene expression phenotypes and severity of atherosclerotic lesions in the left anterior descending-left circumflex bifurcation artery. These data suggested diet quality modulated the response to atorvastatin therapy in colonic mucosa, and these effects were unrelated to atherosclerotic lesion development.
Competing Interests: Competing Interests statement The authors declare no competing interests.
(Copyright © 2021 Tufts University. Published by Elsevier Inc. All rights reserved.)

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R01 DK061931 United States DK NIDDK NIH HHS; R01 DK068271 United States DK NIDDK NIH HHS; T32 GM108563 United States GM NIGMS NIH HHS; T32 HL125232 United States HL NHLBI NIH HHS

Keywords: Atherosclerosis; Colon; Dietary patterns; Inflammation; Ossabaw pig; Statin

0 (Cholesterol, Dietary)
0 (Dietary Fats)
0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
A0JWA85V8F (Atorvastatin)

Date Created: 20210111 Date Completed: 20210617 Latest Revision: 20220506

20240829

PMC8994518

10.1016/j.jnutbio.2020.108570

33429036