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.
Highlights
Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the world [1].The residual risk of continuing to suffer from this metabolic disorder, even after using all current therapies, remains high [2]
As postprandial lipemia is a dynamic, non-steady-state condition in which humans spend the majority of their time [34], miRNAs are potential candidates for therapeutic interventions [35]
Seventy-three miRNAs showed differential expression between any of the treatments after the dietary challenge. These results prove our hypothesis that c-miRNAs could be modulated by postprandial lipemia (Figure 2A)
Summary
The residual risk of continuing to suffer from this metabolic disorder, even after using all current therapies, remains high [2] Lifestyle changes such as diet and exercise generally help, they are often insufficient to achieve healthy lipid profiles, requiring the use of therapeutic treatments to improve plasma lipid levels [3]. The postprandial state is a dynamic period of metabolic traffic, biosynthesis, and oxidative metabolism of absorbed substrates such as glucose, lipids, proteins, and other biomolecules contained in the diet. During this period, the body responds with compensatory and adaptive mechanisms and manages short-term disturbances to restore homeostasis. Developed countries often use high-energy diets and exhibit limited energy expenditure, resulting in prolonged metabolic, oxidative, and immune imbalance [4], associated with CVD development [5]
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