Variations in HDL-carried miR-223 and miR-135a concentrations after consumption of dietary trans fat are associated with changes in blood lipid and inflammatory markers in healthy men - an exploratory study

ABSTRACT

A high consumption of trans fatty acids (TFAs) is associated with an increased risk of cardiovascular diseases (CVDs). High-density lipoproteins (HDLs) have many cardioprotective properties and transport functional microRNAs (miRNAs) to recipient cells. We hypothesized that dietary TFAs modify the HDL-carried miRNA profile, therefore modulating its cardioprotective properties. We assessed whether consumption of dietary TFAs modifies HDL-carried miR-223-3p and miR-135a-3p concentration and the inter-relationship between diet-induced changes in HDL-carried miRNA concentration and CVD risk markers. In a double blind, randomized, crossover, controlled study, 9 men were fed each of 3 experimental isoenergetic diets: 1) High in industrial TFA (iTFA; 3.7% energy); 2) High in TFA from ruminants (rTFA; 3.7% energy); 3) Low in TFA (control; 0.8% energy) for 4 weeks each. HDLs were isolated by ultracentrifugation and miRNAs were quantified by RT-qPCR. Variations in HDL-miR-223-3p concentration were negatively correlated with variations in HDL-cholesterol after the iTFA diet (r_s = 0.82; P = 0.007), and positively correlated with variations in C-reactive protein concentration after the rTFA diet (r_s = 0.75; P = 0.020). Variations in HDL-miR-135a-3p concentration were positively correlated with variations in total triglyceride (TG) concentration following the iTFA diet (r_s = −0.82; P = 0.007), and with variations in low-density lipoprotein (LDL)-TG concentration following the rTFA diet (r_s = 0.83; P = 0.005), compared to the control diet. However, the consumption of dietary TFAs has no significant unidirectional impact on HDL-carried miR-223-3p and miR-135a-3p concentrations. Our results suggest that the variability in the HDL-carried miRNAs response to TFA intake, by being associated with variations in CVD risk factors, might reflect physiological changes in HDL functions.

KEYWORDS:

• Blood miRNA
• CVD
• HDL
• microRNA
• TFA

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

We are grateful to the metabolic kitchen, nurses and laboratory staff from the Institute of Nutrition and Functional Foods (INAF) of the Department of nutrition of Université Laval for their dedicated work during the nutritional trial. We express our gratitude to Céline Bélanger, Chicoutimi Hospital, for her thoughtful revision of the manuscript.

Funding

This study was supported by the Réseau de recherche en santé cardiométabolique, diabète et obésité (CMDO) of the Fonds de recherche du Québec en santé (FRQS), the Étienne-Le Bel Clinical research center (affiliated with the hospital of Université de Sherbrooke), and the ECOGENE-21 Clinical Research Center (principal investigator: Daniel Gaudet, MD, PhD, Université de Montréal). During this research, VD was recipient of a doctoral research award from the Faculté de médecine et des sciences de la santé (FMSS) of Université de Sherbrooke, and was subsequently recipient of a doctoral research award from FRQS. During this research, SPG was recipient of a doctoral research award from the Canadian Institutes of Health Research (CIHR). LB is a junior research scholar from the FRQS, and a member of the FRQS-funded Center de recherche du CHUS (affiliated to the Center hospitalier universitaire de Sherbrooke). The clinical trial was supported by an unrestricted grant from the Dairy Farmers of Canada, by Novalait Inc., and by a grant from the Natural Sciences and Engineering Research Council of Canada. The Canadian Dairy Commission donated the low-rTFA control butter; Provigo-Loblaws donated the foods used in the clinical trial.

Authors contribution

LB designed miRNA study; RG, FC and PC participated to miRNA study design; BL designed nutritional trial; VD and SPG (miRNA study), and BL (nutritional trial) conducted research; VD, SPG and LB analyzed/interpreted data; VD wrote the manuscript; LB had primary responsibility for final content. All authors have contributed to this work, read, and approved the final manuscript.