Abnormal fatty acid metabolism and availability are landmarks of metabolic diseases, which in turn are associated with aberrant DNA methylation profiles. To understand the role of fatty acids in disease epigenetics, we sought DNA methylation profiles specifically induced by arachidonic (AA) or oleic acid (OA) in cultured cells and compared those with published profiles of normal and diseased tissues. THP-1 monocytes were stimulated with AA or OA and analyzed using Infinium HumanMethylation450 BeadChip (Illumina) and Human Exon 1.0 ST array (Affymetrix). Data were corroborated in mouse embryonic fibroblasts. Comparisons with publicly available data were conducted by standard bioinformatics. AA and OA elicited a complex response marked by a general DNA hypermethylation and hypomethylation in the 1–200 μM range, respectively, with a maximal differential response at the 100 μM dose. The divergent response to AA and OA was prominent within the gene body of target genes, where it correlated positively with transcription. AA-induced DNA methylation profiles were similar to the corresponding profiles described for palmitic acid, atherosclerosis, diabetes, obesity, and autism, but relatively dissimilar from OA-induced profiles. Furthermore, human atherosclerosis grade-associated DNA methylation profiles were significantly enriched in AA-induced profiles. Biochemical evidence pointed to β-oxidation, PPAR-α, and sirtuin 1 as important mediators of AA-induced DNA methylation changes. In conclusion, AA and OA exert distinct effects on the DNA methylome. The observation that AA may contribute to shape the epigenome of important metabolic diseases, supports and expands current diet-based therapeutic and preventive efforts.

Most of the active pharmaceutical compounds are often prone to display low bioavailability and biological degradation represents an important drawback. Due to the above, the development of a drug delivery system (DDS) that enables the introduction of a pharmaceutical compound through the body to achieve a therapeutic effect in a controlled manner is an expanding application. Henceforth, new strategies have been developed to control several parameters considered essential for enhancing delivery of drugs. Nanostructure synthesis by microemulsions (ME) consist of enclosing a substance within a wall material at the nanoscale level, allowing to control the size and surface area of the resulting particle. This nanotechnology has shown the importance on targeted drug delivery to improve their stability by protecting a bioactive compound from an adverse environment, enhanced bioavailability as well as controlled release. Thus, a lower dose administration could be achieved by minimizing systemic side effects and decreasing toxicity. This review will focus on describing the different biocompatible nanostructures synthesized by ME as controlled DDS for therapeutic purposes.

G-protein-coupled receptors (GPCRs) play a crucial role in the gene regulation of processes related to the response to different types of stress in fungi. These receptors act as sensors of extracellular signals and transmit the information to the interior of the cell through G-proteins. In the presence of different and specific types of stresses, GPCRs activate signaling cascades that culminate in the activation of transcription factors, which regulate the expression of genes associated with the stress response, including those induced by changes in environmental pH. GPCR-mediated gene regulation allows fungi to adapt to adverse conditions such as osmotic, thermal, oxidative, or nutritional stress, as well as fluctuations in environmental pH. This review focuses on the understanding of how GPCRs modulate the stress response in fungi and their crucial role in advancing our knowledge of the physiology and adaptability of these microorganisms in their changing environment.

Late embryogenesis abundant (LEA) proteins are a large protein family that mainly function in protecting cells from abiotic stress, but these proteins are also involved in regulating plant growth and development. In this study, we performed a functional analysis of LEA13 and LEA30 from Arabidopsis thaliana. The results showed that the expression of both genes increased when plants were subjected to drought-stressed conditions. The insertional lines lea13 and lea30 were identified for each gene, and both had a T-DNA element in the regulatory region, which caused the genes to be downregulated. Moreover, lea13 and lea30 were more sensitive to drought stress due to their higher transpiration and stomatal spacing. Microarray analysis of the lea13 background showed that genes involved in hormone signaling, stomatal development, and abiotic stress responses were misregulated. Our results showed that LEA proteins are involved in drought tolerance and participate in stomatal density.

Background: The signals that determine atherosclerosis‐specific DNA methylation profiles are only partially known. We previously identified a 29‐bp DNA motif (differential methylation motif [ DMM] ) proximal to CpG islands ( CGI s) that undergo demethylation in advanced human atheromas. Those data hinted that the DMM docks modifiers of DNA methylation and transcription. Methods and Results: We sought to functionally characterize the DMM . We showed that the DMM overlaps with the RNA polymerase III –binding B box of Alu short interspersed nuclear elements and contains a DR 2 nuclear receptor response element. Pointing to a possible functional role for an Alu DMM , CGI s proximal (<100 bp) to near‐intact DMM –harboring Alu are significantly less methylated relative to CGI s proximal to degenerate DMM –harboring Alu or to DMM ‐devoid mammalian‐wide interspersed repeat short interspersed nuclear elements in human arteries. As for DMM ‐binding factors, LXRB (liver X receptor β) binds the DMM in a DR 2‐dependent fashion, and LXR (liver X receptor) agonists induce significant hypermethylation of the bulk of Alu in THP ‐1 cells. Furthermore, we describe 3 intergenic long noncoding RNA s that harbor a DMM , are under transcriptional control by LXR agonists, and are differentially expressed between normal and atherosclerotic human aortas. Notably, CGI s adjacent to those long noncoding RNA s tend to be hypomethylated in symptomatic relative to stable human atheromas. Conclusions: Collectively, the data suggest that a DMM is associated with 2 distinct methylation states: relatively low methylation of in cis CGI s and Alu element hypermethylation. Based on the known atheroprotective role of LXR s, we propose that LXR agonist–induced Alu hypermethylation, a landmark of atherosclerosis, is a compensatory rather than proatherogenic response.

We have previously shown that blood global DNA methylation (DNAm) differs between postprandial state (PS) and fasting state (FS) and is associated with BMI and polyunsaturated fatty acid (PUFA) (negatively and positively, respectively) in 12 metabolically healthy adult Mexican men (AMM cohort) equally distributed among conventional BMI classes. Here, we detailed those associations at CpG dinucleotide level by exploiting the Infinium methylation EPIC array (Illumina). We sought differentially methylated CpG (dmCpG) that were (1) associated with BMI (BMI-dmCpG) and/or fatty acids (FA) (FA-dmCpG) in FS or PS and (2) different across FS and PS within a BMI class. BMI-dmCpG and FA-dmCpG were more numerous in FS compared to PS and largely prandial state-specific. For saturated and monounsaturated FA, dmCpG overlap was higher across than within the respective saturation group. Several BMI- and FA-dmCpG mapped to genes involved in metabolic disease and in some cases matched published experimental data sets. Notably, SETDB1 and MTHFS promoter dmCpG could explain the previously observed associations between global DNAm, PUFA content, and BMI in FS. Surprisingly, overlap between BMI-dmCpG and FA-dmCpG was limited and the respective dmCpG were differentially distributed across functional genomic elements. BMI-dmCpG showed the highest overlap with dmCpG of the saturated FA palmitate, monounsaturated C20:1 and PUFA C20:2. Of these, selected promoter BMI-dmCpG showed opposite associations with palmitate compared to C20:1 and C20:2. As for the comparison between FS and PS within BMI classes, dmCpG were strikingly more abundant and variably methylated in overweight relative to normoweight or obese subjects (∼70–139-fold, respectively). Overweight-associated dmCpG-hosting genes were significantly enriched in targets for E47, SREBP1, and RREB1 transcription factors, which are known players in obesity and lipid homeostasis, but none overlapped with BMI-dmCpG. We show for the first time that the association of BMI and FA with methylation of disease-related genes is distinct in FS and PS and that limited overlap exists between BMI- and FA-dmCpG within and across prandial states. Our study also identifies a transcriptional regulation circuitry in overweight that might contribute to adaptation to that condition or to transition to obesity. Further work is necessary to define the pathophysiological implications of these findings.