A microRNA expression signature of the postprandial state in response to a high-saturated-fat challenge

Abstract

The postprandial hypertriglyceridemia is an important and largely silent disturbance involved in the genesis of numerous pathological conditions. Exaggerated and prolonged states of postprandial hypertriglyceridemia are frequently related to the ingestion of meals enriched in saturated fatty acids (SFAs). MicroRNAs are noncoding RNAs that function as gene regulators and play significant roles in both health and disease. However, differential miRNA expression between fasting and postprandial states has never been elucidated. Here, we studied the impact of a high-saturated-fat meal, mainly rich in palmitic acid, on the miRNA signature in peripheral blood mononuclear cells (PBMCs) of nine male healthy individuals in the postprandial period by using a two-step analysis: miRNA array and validation through quantitative real-time polymerase chain reaction. Compared with miRNA expression signature in PBMCs at fasting, 36 miRNAs were down-regulated and 43 miRNAs were up-regulated in PBMCs at postprandial hypertriglyceridemic peak. Six chromosomes (3, 7, 8, 12, 14 and 19) had nearly half (48.1%) of dysregulated miRNA-gene-containing regions. Down-regulated miR-300 and miR-369-3p and up-regulated miR-495-3p, miR-129-5p and miR-7-2-3p had the highest number of target genes. The differentially expressed miRNAs and their predicted target genes involved pathways in cancer, MAPK signaling pathway, endocytosis and axon guidance. Only down-regulated miRNAs notably targeted PI3K-Akt signaling pathways, whereas only up-regulated miRNAs targeted focal adhesion, Wnt signaling pathway, transcriptional misregulation in cancer and ubiquitin-mediated proteolysis. This is the first study of miRNA expression analysis of human PBMCs during postprandial hypertriglyceridemia and offers insight into new potential mechanisms by which dietary SFAs influence health or disease.

Postprandial Circulating miRNAs in Response to a Dietary Fat Challenge

“…Previous studies have evaluated the postprandial regulation of tissue miRNAs in different models, including miRNAs involved in insulin pathways in fish liver [21], or in endothelial cells in response to triglyceride-rich lipoproteins isolated from subjects after consumption of a high-fat meal [22]. In addition, in response to a postprandial high-saturated-fat challenge in healthy individuals, changes in a signature of miRNAs in peripheral blood mononuclear cells were reported [23]. However, there is scarce information about the levels of circulating miRNAs in response to postprandial dietary fat challenge.…”

Impact of Polypharmacy on Candidate Biomarker miRNomes for the Diagnosis of Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Striking Back on Treatments

“…To elevate biomarker screenings of FM and ME/CFS based on miRNA profiles, complex stratified analysis to filter out potential drug and other confounding variables will be required. The complexity and limitations of this analysis is served by the fact that miRNA expression responds to many cues, such as exercise and diet, hormones, sex, and aging [38,39,40,41,42,43].…”

“…To minimize potential environmental confounding factors, healthy participants are often population-matched by sex, age, and quite frequently BMI (body mass index) with the participating patient group. Careful selection of participants and proper study design are key factors in identifying miRNA disease-associated profiles (disease miRNomes), as miRNA levels also change in response to hormone challenges, during aging and metabolic states [38,39,40,41], including the post-prandial estate [42]. In the context of FM and ME/CFS, since miRNomes change with exercise [43], inclusion of sedentary control groups would be desirable.…”

Impact of Polypharmacy on Candidate Biomarker miRNomes for the Diagnosis of Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Striking back on Treatments

“…To elevate biomarker screenings of FM and ME/CFS based on miRNA profiles, complex stratified analysis to filter out potential drug and other confounding variables will be required. The complexity and limitations of this analysis is served by the fact that miRNA expression respond to many cues, such as exercise and diet, hormone, sex and aging [38][39][40][41][42][43].…”

“…To minimize potential environmental confounding factors healthy participants are often population matched by sex, age; and quite frequently by BMI (body mass index) with the participating patient group. Careful selection of participants and proper study design are key factors in identifying miRNA disease-associated profiles (disease miRNomes), as miRNA levels also change in response to hormone challenges, during aging and metabolic states [38][39][40][41], including the postprandial estate [42]. In the context of FM and ME/CFS, since miRNomes change with exercise [43], inclusion of sedentary control groups would be desirable.…”