Using metabolic profiling and gene expression analyses to explore molecular effects of replacing saturated fat with polyunsaturated fat—a randomized controlled dietary intervention study

Abstract

Background Replacing dietary saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFA) reduces the plasma low-density lipoprotein (LDL) cholesterol and subsequently the risk of cardiovascular disease. However, beyond changes in LDL cholesterol, we lack a complete understanding of the physiologic alterations that occur when improving dietary fat quality. Objectives The aim of this study was to gain knowledge of metabolic alterations paralleling improvements in the fat quality of the diet. Methods We recently conducted an 8-wk, double-blind, randomized controlled trial replacing SFAs with PUFAs in healthy subjects with moderate hypercholesterolemia (n = 99). In the present substudy, we performed comprehensive metabolic profiling with multiple platforms (both nuclear magnetic resonance- and mass spectrometry-based technology) (n = 99), and analyzed peripheral blood mononuclear cell gene expression (n = 95) by quantitative real-time polymerase chain reaction. Results A large number of lipoprotein subclasses, myristoylcarnitine and palmitoylcarnitine, and kynurenine were reduced when SFAs were replaced with PUFAs. In contrast, bile acids, proprotein convertase subtilisin/kexin type 9, acetate, and acetoacetate were increased by the intervention. Some amino acids were also altered by the intervention. The mRNA levels of LXRA and LDLR were increased, in addition to several liver X receptor α target genes and genes involved in inflammation, whereas the mRNA levels of UCP2 and PPARD were decreased in peripheral blood mononuclear cells after replacing SFAs with PUFAs. Partial least squares-discriminant analysis showed that the 30 most important variables that contributed to class separation spanned all classes of biomarkers, and was in accordance with the univariate analysis. Conclusions Applying metabolomics in randomized controlled dietary intervention trials has the potential to extend our knowledge of the biological and molecular effects of dietary fat quality. This study was registered at clinicaltrials.gov as NCT 01679496.

An Isocaloric Nordic Diet Modulates RELA and TNFRSF1A Gene Expression in Peripheral Blood Mononuclear Cells in Individuals with Metabolic Syndrome—A SYSDIET Sub-Study

“…None of the gene transcripts encoding proteins related to lipid metabolism were changed by the ND compared to the CD. We have previously shown that exchanging SFA with PUFA reduced total cholesterol and LDL-C by 9% and 11%, respectively, among subjects with slightly elevated cholesterol [29], and changed the PBMC expression levels of several lipid metabolism-related genes [30]. The reason why we did not observe any changes in lipid metabolism-related genes in the present study, may be due to the smaller effect of the ND on the lipid profile as previously shown [16].…”

Nutrition and the Immune System: A Complicated Tango

“…Assessing the bidirectional relationship between diet and the immune system can be undertaken utilizing multiple approaches. In human intervention studies, investigators have assessed the impact of bioenergetic status [1], isolated nutrients [2][3][4][5][6], and dietary patterns, such as the Mediterranean Diet [7,8], in both controlled feeding and free-living intervention studies on numerous indices of immune function (e.g., circulating cytokines, high-sensitivity C-reactive Protein, antibodies, tissue-specific…”

Associations between dietary patterns and gene expression pattern in peripheral blood mononuclear cells: A cross-sectional study

“…See Supplemental Methods for detailed description of PBMC isolation, RNA extraction, microarray analysis and gene expression pre-processing steps. Briefly, we collected PBMCs and extracted RNA according to standardized protocols [6]. The subsequent microarray gene expression analyses were performed using HumanHT-12 Expression BeadChips (Illumina Inc., CA, USA), and followed standard Illumina protocol (Illumina Inc., CA, USA).…”