Postprandial Circulating miRNAs in Response to a Dietary Fat Challenge

Abstract

Postprandial lipemia has many physiopathological effects, some of which increase the risk of cardiovascular disease. MicroRNAs (miRNAs) can be found in almost all biological fluids, but their postprandial kinetics are poorly described. We aimed to profile circulating miRNAs in response to a fat challenge. In total, 641 circulating miRNAs were assessed by real-time PCR in plasmas from mice two hours after lipid gavage. Mice with intestine-specific loss of Dicer were screened to identify potential miRNAs released by the intestine. A total of 68 miRNAs were selected for further validation. Ten circulating miRNAs were finally validated as responsive to postprandial lipemia, including miR-206-3p, miR-543-3p, miR-466c-5p, miR-27b-5p, miR-409-3p, miR-340-3p, miR-1941-3p, miR-10a-3p, miR-125a-3p, and miR-468-3p. Analysis of their possible tissues of origin/target showed an enrichment of selected miRNAs in liver, intestine, brain, or skeletal muscle. miR-206, miR-27b-5p, and miR-409-3p were validated in healthy humans. Analysis of their predicted target genes revealed their potential involvement in insulin/insulin like growth factor (insulin/IGF), angiogenesis, cholecystokinin B receptor signaling pathway (CCKR), inflammation or Wnt pathways for mice, and in platelet derived growth factor (PDGF) and CCKR signaling pathways for humans. Therefore, the current study shows that certain miRNAs are released in the circulation in response to fatty meals, proposing them as potential novel therapeutic targets of lipid metabolism.

Intestinal miRNAs regulated in response to dietary lipids

“…Thus, further clarification is needed regarding the miRNAs acting in the intestinal compartment, along with their target genes and the regulatory networks that are affected. Tissue specific Dicer KO models have been used in some studies to assess the importance of miRNAs in intestinal homeostasis [15][16][17][18] , as well as their involvement in lipid metabolism [19][20][21] . While the primary role of miRNAs seems to be the 'fine-tuning' of gene expression, it is under conditions of stress that the functions of miRNAs become especially pronounced, underscoring their roles in disease 22 .…”

SARS‐CoV‐2: What is known and what there is to know—Focus on coagulation and lipids

“…Such a pre-coating of the endothelium by TRPs may therefore lead to a more available endothelium for SARS-CoV-2 virus spread. 42 Against this background, other prior observations could become important again; SARS-CoV-2 infection gives indeed more complications among black people (racial disparity), likely due from ethnic-dependent differences in nitric oxide generation and paracrine recovery from oxidative stress.…”

Intestinal Lipid Metabolism Genes Regulated by miRNAs

“…The intestine is considered as the "gatekeeper" of intestinal lipid absorption (Krieger, 2001) and miRNAs are relevant players in lipid metabolism (Briand et al, 2016;Mantilla-Escalante et al, 2019), with peculiar roles under stress conditions (Small and Olson, 2011). Having these two concepts in mind, a mouse model lacking miRNAs in epithelial intestinal cells was created by backcrossing Dicer1 loxP / loxP (The Jackson Laboratories, Bar Harbor, ME, United States) and Villin-cre mice (The Jackson Laboratories), showing a remarkable reduction of Dicer1 gene expression in the small intestine and intestinal organoids compared to WT mice ( Figures 1A,B).…”

“…MiRNAs are small (19-25 nucleotides) non-coding RNA molecules, which modulate the activity of hundreds of genes and different pathways related to key biological processes in enterocytes, such as differentiation, proliferation and apoptosis (Bartel, 2009;Gadecka and Bielak-Zmijewska, 2019). Small intestine miRNAs are likely engaged in the regulation of processes such as energy homeostasis, lipid metabolism and HFD-induced weight increase (Briand et al, 2016;Mantilla-Escalante et al, 2019). MiRNAs generally repress the expression of target-genes in lipid metabolism-related pathways, such as insulin signaling, ketogenesis and homeostasis of cholesterol (Li et al, 2020;Wu et al, 2020).…”