Indeed, a feature of miRNA function is that a single miRNA can SJN 2511 simultaneously bind and repress multiple target genes; likewise, the possibility that a single mRNA be targeted by multiple miRNAs provides mechanisms to synchronize the coordinated regulation of a large suite of transcripts that govern an entire biological process, in turn resulting in strong phenotypic output. Pharmacological modulation of miRNA activity has received special attention from the scientific and clinical audience as a novel approach to treat disease by modulating entire biological pathways. Indeed, numerous pharmacological tools have been developed to target miRNA pathways ; promising results have been reported in human clinical trials to either inhibit their Masitinib action or as miRNA replacement therapy. Dietary modulation of miRNA action is an interesting alternative to the former approaches. Our results show for the first time that different types of fatty acid during early pregnancy not only modulate the expression of miRNAs in liver and adipose tissue of pregnant rats but also influence short- and long-term miRNA expression in their offspring. In conclusion, our data add novel in vivo evidence to the notion that fatty acids can modulate miRNA expression in a tissue-specific and temporally-restrained manner. We also show that the type of fatty acid consumed by the mother during early pregnancy elicits epigenetic mechanisms through miRNAs modulation in offspring. One important feature of our contribution is that we comparatively assessed the effects of five diets containing different fatty acid profiles. The precise molecular mechanism underlying the changes in miRNA expression in pregnant mothers and their adult offspring induced by a particular type of fatty acid deserve further investigation. Yet, our data suggest that dietary fatty acid modulation of miRNA expression might theoretically be a viable option to accompany current pharmacological therapy targeting endogenous miRNAs. Leptin is a small 16 kDa peptide secreted by adipose tissue that, in physiological conditions, feeds back to inform the central nervous system about the status of peripheral energy reserves, thereby regulating appetite and energy expenditure. The knowledge about its biological actions increased substantially over the last decades and it is now known that leptin also exerts an important role on sympathetic nerve activity, immune function, cardiovascular and renal systems. The biological action of leptin depends on its interaction with a family of class I cytokine receptors identified as Ob-Ra to Ob-Rf. The full-length leptin receptor, Ob-Rb, is highly expressed in the hypothalamus; however, its expression has been demonstrated in other tissues, including blood vessels and the kidneys. In the kidneys, leptin is filtered and then taken up by the megalin receptor in the proximal convolute tubule cells and almost no leptin is found in the urine.