Dietary lipids and modulation of microRNAs

In 2015, we studied whether specific microRNAs, related to our circadian system (biological clock) could alter their expression by dietary lipids.

The increased prevalence of cardiovascular diseases (CVDs) has been hypothesized to be the result of increased exposure to a host of atherogenic environmental factors, paramount among them being unhealthy dietary habits. Long-chain n-3 polyunsaturated fatty acids have been shown to have cardioprotective effects, partially due to their ability to regulate gene expression. In this regard, increasing attention has been devoted to the role of miRNAs as regulators of multiple metabolic pathways whose deregulation has been associated with CVD risk. In this work, we investigated whether miRNA expression was regulated by docosahexaenoic acid, conjugated linoleic acid, and cholesterol in Caco-2 cells.

The modulated miRNAs, miR-107 was differentially expressed by all treatments and this modulation was independent of its hosting gene, PANK1, possibly through its own promoter, which contains binding sites for metabolically relevant transcription factors. Among the putative target genes of miR-107, we found some genes with key roles in circadian rhythm. Specifically, we demonstrated that the binding of miR-107 to the CLOCK gene results in the deregulation of the circadian rhythm of the cells.

Since chronodisruption has been linked to metabolic disorders such as type 2 diabetes, atherosclerosis, obesity, and CVD, our findings suggest that miR-107 could represent a new approach for the pharmacological treatment of these diseases.

The original publication can be found in PUBMEB, NIH National Library of Medicine.