A hierarchical filtering approach was used to identify novel inhibitors

Fatty acid supplementation during development could affect epigenetic gene regulation by inducing transcription of specific genes during critical ontogenic periods, during which tissue-specific marks may be initiated. Therefore, studies on the potential epigenetic mechanism involved in these findings are warranted. Although the evidence that fatty acids affect epigenetic gene regulation is limited, several findings indicate that the quantity and quality of fatty acids consumed by mothers during pregnancy and lactation can induce permanent changes in gene expression and metabolism in their offspring. There is in vitro evidence that certain fatty acids could modulate the expression of miRNA in different cell types. However, in vivo evidence of any one of these effects is limited. It was recently shown that maternal consumption of a high-fat diet MK-0683 customer reviews affects early lipid metabolism of LY2109761 offspring by modulating the expression of hepatic ��-oxidation-related genes and that miRNAs can contribute to metabolic disturbances in adult life. Whether this effect is influenced by the type of fatty acids used in the diet was not evaluated, but these results suggest that a diet containing high proportions of certain fatty acids could modulate the expression of specific miRNAs in the offspring, which may in turn lead to metabolic disorders. The present study was designed to investigate whether consumption of different types of fatty acids during the first 12 days of pregnancy in rats influence the expression of miRNAs in parental tissues and whether these precocious exposures influence miRNAs expression in offspring. Depending on the tissue evaluated, different parental miRNAs were found to be modulated by different type of fatty acids. Even after 12 month after switch to a normal chow diet, offspring adult liver exhibited a miRNA expression influence by the early exposure. Sunflower or soybean oil was added to some diets to meet the minimum requirement for essential fatty acids. The experimental diets were isoenergetic and their composition and proportion of fatty acid profiles are shown in S1 Table. The diets were prepared at the beginning of the experiment and were kept at -20��C fractioned in daily portions. Every 24 h, fresh diet was provided and daily food intake was estimated periodically. After 12 days on an experimental diet, 6�C8 rats from each group were sacrificed and the remaining pregnant rats were given standard pellet diet until the end of the study. During lactation, pups were maintained with their mothers until weaning and all litters were culled to 8 pups per dam within 24 h of delivery, by selecting the excess number of pups at random and removing them. Rats always had free access to the assigned diet and tap water.

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