Replacing Saturated Fat with Polyunsaturated Fat Modulates Peripheral Blood Mononuclear Cell Gene Expression and Pathways Related to Cardiovascular Disease Risk Using a Whole Transcriptome Approach

Sunniva V Larsen; Kirsten B Holven; Jacob J Christensen; Arnar Flatberg; Amanda Rundblad; Lena Leder; Rune Blomhoff; Vibeke Telle-Hansen; Marjukka Kolehmainen; Carsten Carlberg; Mari C Myhrstad; Magne Thoresen; Stine M Ulven

doi:10.1002/mnfr.202100633

Replacing Saturated Fat with Polyunsaturated Fat Modulates Peripheral Blood Mononuclear Cell Gene Expression and Pathways Related to Cardiovascular Disease Risk Using a Whole Transcriptome Approach

Mol Nutr Food Res. 2021 Dec;65(24):e2100633. doi: 10.1002/mnfr.202100633. Epub 2021 Nov 15.

Authors

Sunniva V Larsen¹, Kirsten B Holven^{1

2}, Jacob J Christensen^{1

2}, Arnar Flatberg^{3

4}, Amanda Rundblad¹, Lena Leder⁵, Rune Blomhoff^{1

6}, Vibeke Telle-Hansen⁷, Marjukka Kolehmainen⁸, Carsten Carlberg⁹, Mari C Myhrstad⁷, Magne Thoresen¹⁰, Stine M Ulven¹

Affiliations

¹ Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Blindern, Oslo, Norway.
² Department of Endocrinology, Morbid Obesity and Preventive Medicine, Norwegian National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital, Nydalen, Oslo, Norway.
³ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
⁴ Central Administration, St. Olavs Hospital, The University Hospital in Trondheim, Trondheim, Norway.
⁵ Mills AS, Oslo, Norway.
⁶ Department of Clinical Service, Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway.
⁷ Department of Nutrition, Faculty of Health Sciences, Oslo Metropolitan University, St. Olavs Plass, Oslo, Norway.
⁸ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
⁹ School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
¹⁰ Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Blindern, Oslo, Norway.

PMID: 34708513
DOI: 10.1002/mnfr.202100633

Abstract

Scope: The aim of this study is to explore the molecular mechanisms underlying the effect of replacing dietary saturated fat (SFA) with polyunsaturated fat (PUFA) on cardiovascular disease (CVD) risk using a whole transcriptome approach.

Methods and results: Healthy subjects with moderate hypercholesterolemia (n = 115) are randomly assigned to a control diet (C-diet) group or an experimental diet (Ex-diet) group receiving comparable food items with different fatty acid composition for 8 weeks. RNA isolated from peripheral blood mononuclear cells (PBMCs) at baseline and after 8 weeks of intervention is analyzed by microarray technology (n = 95). By use of a linear regression model (n = 92), 14 gene transcripts are differentially altered in the Ex-diet group compared to the C-diet group. These include transcripts related to vascular smooth muscle cell proliferation, low-density lipoprotein receptor folding, and regulation of blood pressure. Furthermore, pathways mainly related to immune response and inflammation, signal transduction, development, and cytoskeleton remodeling, gene expression and protein function, are differentially enriched between the groups.

Conclusion: Replacing dietary SFA with PUFA for 8 weeks modulates PBMC gene expression and pathways related to CVD risk in healthy subjects with moderate hypercholesterolemia.

Keywords: LDL cholesterol; cardiovascular disease risk; dietary fat quality; gene expression; inflammation.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Cardiovascular Diseases* / genetics
Dietary Fats / adverse effects
Fatty Acids
Humans
Leukocytes, Mononuclear*
Transcriptome

Substances

Dietary Fats
Fatty Acids