Silybin restores glucose uptake after tumour necrosis factor-alpha and lipopolysaccharide stimulation in 3T3-L1 adipocytes.

Obesity is associated with a low-grade chronic inflammatory process characterized by higher circulating TNFα levels, thus contributing to insulin resistance. This study evaluated the effect of silybin, the main bioactive component of silymarin, which has anti-inflammatory properties, on TNFα levels and its impact on glucose uptake in the adipocyte cell line 3T3-L1 challenged with two different inflammatory stimuli, TNFα or lipopolysaccharide (LPS). Silybin's pre-treatment effect was evaluated in adipocytes pre-incubated with silybin (30 or 80 µM) before challenging with the inflammatory stimuli (TNFα or LPS). For the post-treatment effect, the adipocytes were first challenged with the inflammatory stimuli and then post-treated with silybin. After treatments, TNFα production, glucose uptake, and GLUT4 protein expression were determined. Both inflammatory stimuli increased TNFα secretion, diminished GLUT4 expression, and significantly decreased glucose uptake. Silybin 30 µM only reduced TNFα secretion after the LPS challenge. Silybin 80 µM as post-treatment or pre-treatment decreased TNFα levels, improving glucose uptake. However, glucose uptake enhancement induced by silybin did not depend on GLUT4 protein expression. These results show that silybin importantly reduced TNFα levels and upregulates glucose uptake, independently of GLUT4 protein expression.

Neuroprotection mediated by prolactin against streptozotocin injury in brain rat areas.

Prolactin has been recognized as neuroprotective hormone against various types of neuronal damage. This study was aimed to determine if prolactin protects against streptozotocin injury. A series of experiments were performed to determine neuronal survival by counting total neurons in medial hippocampus cortex and cerebellum. Astrogliosis was determined by immunofluorescence assays using GFAP, and behavioral improvement by prolactin after neuronal damage was determined by open-field and light-dark box tests. Results demonstrated that prolactin induced significant neuronal survival in both the hippocampus and cortex, but not in the cerebellum. No increase in astrogliosis was identified, but a significant reduction in anxiety levels was observed. Overall data indicate that prolactin may protect against a complex form of cell damage including oxidant stress and metabolic disruption by streptozotocin. Prolactin may be helpful strategy in the treatment of neuronal damage in neurological diseases.

Sperm melatonin receptors, seminal plasma melatonin and semen freezability in goats.

Goat bucks are seasonal breeders that show variation in sperm quality, endogenous melatonin (MLT), and presumably in the expression of MLT receptors on the sperm throughout the year, which may modify sperm freezability. The aim of this study was to determine whether sperm freezability is associated with (i) endogenous melatonin levels in seminal plasma and (ii) the expression of sperm plasma membrane melatonin receptors (MT1, MT2). To evaluate this, spermatozoa from seven Saanen goat bucks were cryopreserved throughout the year in Mexico using a standard freezing protocol. Seminal plasma MLT concentrations were determined by ELISA and the expression and localization of MT1 and MT2 were detected by immunocytochemistry and confirmed by western blotting. The recovery rate of progressive motility after thawing was higher in spring than autumn and winter; in contrast, the F pattern (CTC assay) was higher in winter than in the other seasons. A proportional increase in the AR pattern (CTC assay) was smaller in winter than in the other seasons and the proportion of sperm showing high plasma membrane fluidity was higher in spring than in summer and autumn. The seminal plasma MLT concentrations showed no significant interseasonal differences. The MT1 receptor was immunolocalised at the apical region of the sperm head, while MT2 was mainly localised in the neck. The relative expression of MLT receptors showed significant differences between summer and winter for all bands, except at 75 kDa of MT2. In conclusion, there was an association between the relative expression of MT1 and MT2 receptors throughout the year and sperm freezability in goat bucks in México. Post-thaw sperm quality is enhanced in semen samples collected during breeding season.

Synergistic neuroprotective action of prolactin and 17ß-estradiol on kainic acid-induced hippocampal injury and long-term memory deficit in ovariectomized rats.

PURPOSE: The neuroprotective actions of the ovarian hormone 17ß-estradiol (E2) against different brain lesions have been constantly confirmed in a variety of models including kainic acid (KA) lesions. Similarly, the pituitary hormone prolactin (PRL), traditionally associated with lactogenesis, has recently been linked to a large diversity of functions, including neurogenesis, neuroprotection, and cognitive processes. While the mechanisms of actions of E2 as regards its neuroprotective and behavioral effects have been extensively explored, the molecular mechanisms of PRL related to these roles remain under investigation. The current study aimed to investigate whether the simultaneous administration of PRL and a low dose of E2 prevents the KA-induced cognitive deficit and if this action is associated with changes in hippocampal neuronal density. METHODS: Ovariectomized (OVX) rats were treated with saline, PRL, and/or E2 in the presence or absence of KA. Neuroprotection was assessed by Nissl staining and neuron counting. Memory was evaluated with the novel object recognition test (NOR). RESULTS: On their own, both PRL and E2 prevented short- and long-term memory deficits in lesioned animals and exerted neuroprotection against KA-induced excitotoxicity in the hippocampus. Interestingly, the combined hormonal treatment was superior to either of the treatments administered alone as regards improving both memory and neuronal survival. CONCLUSION: Taken together, these results point to a synergic effect of E2 and PRL in the hippocampus to produce their behavioral, proliferative, and neuroprotective effects.

Impact of DEHP exposure on female reproductive health: Insights into uterine effects.

Several endocrine disrupting compounds released from plastics, including polyfluoroalkyl substances, bisphenols, flame retardants, phthalates and others, are of great concern to human health due to their high toxicity. This review discusses the effects of di-(2-ethylhexyl) phthalate (DEHP), the most common member of the phthalate family, on female reproduction. In vitro and in vivo studies link DEHP exposure to impaired hypothalamic-pituitary-ovarian s (HPO) axis function, alteration of steroid-hormone levels and dysregulation of their receptors, and changes in uterine morphophysiology. In addition, high urinary DEPH levels have been associated with several reproductive disorders in women, including endometriosis, fibromyoma, fetal growth restriction and pregnancy loss. These data suggest that DEHP may be involved in the pathophysiology of various female reproductive diseases. Therefore, exposure to these compounds should be considered a concern in clinician surveillance practices for women at reproductive age and should be regulated to protect their health and that of their progeny.

Silymarin Reduced Insulin Resistance in Non-Diabetic Women with Obesity.

Silymarin has ameliorated obesity, type 2 diabetes (T2DM), and insulin resistance (IR) in combination with standard therapy, diet, or exercise in recent studies. Obesity and IR are the main risk factors for developing T2DM and other metabolic disorders. Today, there is a need for new strategies to target IR in patients with these metabolic diseases. In the present longitudinal study, a group of non-diabetic insulin-resistant women with type 1 and type 2 obesity were given silymarin for 12 weeks, with no change in habitual diet and physical activity. We used the Homeostatic Model Assessment for Insulin Resistance Index (HOMA-IR) to determine IR at baseline and after silymarin treatment (t = 12 weeks). We obtained five timepoint oral glucose tolerance tests, and other biochemical and clinical parameters were analyzed before and after treatment. Treatment with silymarin alone significantly reduced mean fasting plasma glucose (FPG) and HOMA-IR levels at 12 weeks compared to baseline values (p < 0.05). Mean fasting plasma insulin (FPI), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (Tg), indirect bilirubin, and C-reactive protein (CRP) levels decreased compared to baseline values, although changes were non-significant. The overall results suggest that silymarin may offer a therapeutic alternative to improve IR in non-diabetic individuals with obesity. Further clinical trials are needed in this type of patient to strengthen the results of this study.

Metabolites from the Andean paramo lichen Cladonia cf. didyma and their effect as photoprotective and antioxidant agents.

5α,8α-peroxyergosteryl divaricatinate (1) is isolated for the first time from acetone extract of the thallus of Cladonia cf. didyma together with condidymic (2), isodidymic (3) and barbatic (4) acids. Their UVB/UVA photoprotective and antioxidant activities were determined along with their cyto- and DNA-protecting actions against OH• damage. Compound 1 showed high UVA, cyto- (%cell viability ca. 82 at 15 µM vs 71 for OH•) and DNA (%DNA-integrity ca. 74 at 100 µM vs 22 for OH•) protecting properties. Compounds 2 and 3 exhibited high UVB (SPF ca. 40) and antioxidant activities (free radical scavenging potency EC50 = 0.6694 and 1.700 mol compound/mol DPPH•; ferric reducing power 0.392 and 0.546, at 500 ppm and inhibited lipid peroxidation); protecting cells (%cell viability ca. 76 at 15 µM) and DNA (%DNA-integrity ca. 57 at 100 µM). Compounds 1 to 3 fulfilled some physicochemical properties to act topically on the skin.

Exploring the Influence of Spacers in EDTA-ß-Cyclodextrin Dendrimers: Physicochemical Properties and In Vitro Biological Behavior.

The synthesis of a new family of ethylenediaminetetraacetic acid (EDTA) core dimers and G0 dendrimers end-capped with two and four ß-cyclodextrin (ßCD) moieties was performed by click-chemistry conjugation, varying the spacers attached to the core. The structure analyses were achieved in DMSO-d6 and the self-inclusion process was studied in D2O by 1H-NMR spectroscopy for all platforms. It was demonstrated that the interaction with adamantane carboxylic acid (AdCOOH) results in a guest-induced shift of the self-inclusion effect, demonstrating the full host ability of the ßCD units in these new platforms without any influence of the spacer. The results of the quantitative size and water solubility measurements demonstrated the equivalence between the novel EDTA-ßCD platforms and the classical PAMAM-ßCD dendrimer. Finally, we determined the toxicity for all EDTA-ßCD platforms in four different cell lines: two human breast cancer cells (MCF-7 and MDA-MB-231), human cervical adenocarcinoma cancer cells (HeLa), and human lung adenocarcinoma cells (SK-LU-1). The new EDTA-ßCD carriers did not present any cytotoxicity in the tested cell lines, which showed that these new classes of platforms are promising candidates for drug delivery.

Alterations of learning and memory are accompanied by alterations in the expression of 5-HT receptors, glucocorticoid receptor and brain-derived neurotrophic factor in different brain regions of an animal model of depression generated by neonatally male treatment with clomipramine in male rats.

Depressive illness has been associated with impaired cognitive processes accompanied by reduced neurotrophin levels, especially brain-derived neurotrophic factor (BDNF), and dysfunctions in the hypothalamic-pituitary-adrenal (HPA) axis. In addition, depression is characterized by a decreased functioning of the serotonergic system due to changes in the activity or expression of its receptors including, most significantly, 5-HT1A, 5-HT2A, and 5-HT3 in brain regions that regulate mood, emotions, and memory, such as the prefrontal cortex, hippocampus, and amygdala. In this regard, rats treated with clomipramine (CMI) in the neonatal stage show depression-like behaviors that persist into adulthood; hence, this constitutes an adequate model of depression for exploring various molecular aspects associated with the etiology of this disorder. This, study, then, was designed to analyze the long-term effects of early postnatal exposure to CMI on the expression of 5-HT1A, 5-HT2A, and 5-HT3 receptors, as well as BDNF and GR in the following brain regions: PFC, amygdala, hippocampus, and hypothalamus, which could be related to alterations in memory and learning, as evaluated using the novel object recognition (NOR) and Morris water maze (MWM). Expression of the 5-HT1A, 5-HT2A, and 5-HT3 receptors, BDNF, and the glucocorticoid receptor (GR) was assessed by RT-qPCR in the four aforementioned brain regions, all of which play important roles in the control of memory and mood. Findings show that neonatal treatment with CMI causes alterations in memory and learning, as indicated by alterations in the results of the MWM and NOR tests. Expression of the 5-HT1A receptor increased in the hippocampus, amygdala, and hypothalamus, but decreased in the PFC, while the 5-HT2A and BDNF receptors decreased their expression in the PFC, amygdala, and hippocampus. There was no change in the expression of the 5-HT3 receptor. In addition, expression of GR in the hippocampus and PFC was low, but increased in the hypothalamus. Taken together, these data show that neonatal CMI treatment produces permanent molecular changes in brain regions related to learning and memory that could contribute to explaining the behavioral alterations observed in this model.

The Effect of Metformin and Carbohydrate-Controlled Diet on DNA Methylation and Gene Expression in the Endometrium of Women with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine disease associated with infertility and metabolic disorders in reproductive-aged women. In this study, we evaluated the expression of eight genes related to endometrial function and their DNA methylation levels in the endometrium of PCOS patients and women without the disease (control group). In addition, eight of the PCOS patients underwent intervention with metformin (1500 mg/day) and a carbohydrate-controlled diet (type and quantity) for three months. Clinical and metabolic parameters were determined, and RT-qPCR and MeDIP-qPCR were used to evaluate gene expression and DNA methylation levels, respectively. Decreased expression levels of HOXA10, GAB1, and SLC2A4 genes and increased DNA methylation levels of the HOXA10 promoter were found in the endometrium of PCOS patients compared to controls. After metformin and nutritional intervention, some metabolic and clinical variables improved in PCOS patients. This intervention was associated with increased expression of HOXA10, ESR1, GAB1, and SLC2A4 genes and reduced DNA methylation levels of the HOXA10 promoter in the endometrium of PCOS women. Our preliminary findings suggest that metformin and a carbohydrate-controlled diet improve endometrial function in PCOS patients, partly by modulating DNA methylation of the HOXA10 gene promoter and the expression of genes implicated in endometrial receptivity and insulin signaling.

The Role of B Cell and T Cell Glycosylation in Systemic Lupus Erythematosus.

Glycosylation is a post-translational modification that affects the stability, structure, antigenicity and charge of proteins. In the immune system, glycosylation is involved in the regulation of ligand-receptor interactions, such as in B-cell and T-cell activating receptors. Alterations in glycosylation have been described in several autoimmune diseases, such as systemic lupus erythematosus (SLE), in which alterations have been found mainly in the glycosylation of B lymphocytes, T lymphocytes and immunoglobulins. In immunoglobulin G of lupus patients, a decrease in galactosylation, sialylation, and nucleotide fucose, as well as an increase in the N-acetylglucosamine bisector, are observed. These changes in glycoisolation affect the interactions of immunoglobulins with Fc receptors and are associated with pericarditis, proteinuria, nephritis, and the presence of antinuclear antibodies. In T cells, alterations have been described in the glycosylation of receptors involved in activation, such as the T cell receptor; these changes affect the affinity with their ligands and modulate the binding to endogenous lectins such as galectins. In T cells from lupus patients, a decrease in galectin 1 binding is observed, which could favor activation and reduce apoptosis. Furthermore, these alterations in glycosylation correlate with disease activity and clinical manifestations, and thus have potential use as biomarkers. In this review, we summarize findings on glycosylation alterations in SLE and how they relate to immune system defects and their clinical manifestations.

Modulatory role of prolactin in type 1 diabetes.

OBJECTIVES: Patients with type 1 diabetes mellitus have been reported to have elevated prolactin levels and a possible relationship between prolactin levels and the development of the disease has been proposed. However, some studies show that prolactin mediates beneficial functions in beta cells. Therefore, we review information on the roles of prolactin in type 1 diabetes mellitus. CONTENT: Here we summarize the functions of prolactin in the immune system and in pancreatic beta cells, in addition, we describe studies related to PRL levels, its regulation and alterations of secretion in patients with type 1 diabetes mellitus. SUMMARY: Studies in murine models have shown that prolactin protects beta cells from apoptosis, stimulates their proliferation and promotes pancreatic islet revascularization. In addition, some studies in patients with type 1 diabetes mellitus have shown that elevated prolactin levels correlate with better disease control. OUTLOOK: Prolactin treatment appears to be a promising strategy to improve beta-cell vascularization and proliferation in transplantation and immunotherapies.

Body mass index implications in intrahepatic cholestasis of pregnancy and placental histopathological alterations.

INTRODUCTION AND OBJECTIVES: Intrahepatic cholestasis is a frequent disease during pregnancy. It is unknown if liver function alterations produce specific placental lesions. The aim of this study was to evaluate placental histopathological changes in patients with intrahepatic cholestasis of pregnancy (ICP), and to explore correlations between the placental histopathology and hepatic function alteration or patient comorbidities, and body mass index. PATIENTS AND METHODS: A retrospective cohort study included women with ICP, most of them showing comorbidities such as overweight/obesity, preeclampsia and gestational diabetes. They were attended at the National Institute of Perinatology in Mexico City for three years. Placental histopathological alterations were evaluated according to the Amsterdam Placental Workshop Group Consensus Statement. Data was analyzed using Graph-Pad Prism 5. RESULTS: The results indicated that the placenta of ICP patients showed many histopathological alterations; however, no correlations were observed between the increase in bile acids or liver functional parameters and specific placental lesions. The most frequent comorbidities found in ICP patients were obesity, overweight and preeclampsia. Surprisingly, high percentage of ICP patients did not respond to UDCA treatment independently of the BMI group to which they belonged. CONCLUSION: The data suggest that ICP contribute to placental lesions. In addition, in patients with normal weight, an increase of chorangiosis and a reduced accelerated villous maturation without syncytial knots were observed in comparison with overweight and obese patients. It is necessary to improve the medical strategies in the treatment and liver disfunction surveillance of ICP patients.

Heparan Sulfate and Sialic Acid in Viral Attachment: Two Sides of the Same Coin?

Sialic acids and heparan sulfates make up the outermost part of the cell membrane and the extracellular matrix. Both structures are characterized by being negatively charged, serving as receptors for various pathogens, and are highly expressed in the respiratory and digestive tracts. Numerous viruses use heparan sulfates as receptors to infect cells; in this group are HSV, HPV, and SARS-CoV-2. Other viruses require the cell to express sialic acids, as is the case in influenza A viruses and adenoviruses. This review aims to present, in a general way, the participation of glycoconjugates in viral entry, and therapeutic strategies focused on inhibiting the interaction between the virus and the glycoconjugates. Interestingly, there are few studies that suggest the participation of both glycoconjugates in the viruses addressed here. Considering the biological redundancy that exists between heparan sulfates and sialic acids, we propose that it is important to jointly evaluate and design strategies that contemplate inhibiting the interactions of both glycoconjugates. This approach will allow identifying new receptors and lead to a deeper understanding of interspecies transmission.

Aptamers as Theragnostic Tools in Prostate Cancer.

Despite of the capacity that several drugs have for specific inhibition of the androgen receptor (AR), in most cases, PCa progresses to an androgen-independent stage. In this context, the development of new targeted therapies for prostate cancer (PCa) has remained as a challenge. To overcome this issue, new tools, based on nucleic acids technology, have been developed. Aptamers are small oligonucleotides with a three-dimensional structure capable of interacting with practically any desired target, even large targets such as mammalian cells or viruses. Recently, aptamers have been studied for treatment and detection of many diseases including cancer. In PCa, numerous works have reported their use in the development of new approaches in diagnostics and treatment strategies. Aptamers have been joined with drugs or other specific molecules such as silencing RNAs (aptamer-siRNA chimeras) to specifically reduce the expression of oncogenes in PCa cells. Even though these studies have shown good results in the early stages, more research is still needed to demonstrate the clinical value of aptamers in PCa. The aim of this review was to compile the existing scientific literature regarding the use of aptamers in PCa in both diagnosis and treatment studies. Since Prostate-Specific Membrane Antigen (PSMA) aptamers are the most studied type of aptamers in this field, special emphasis was given to these aptamers.

Association between Galectin Levels and Neurodegenerative Diseases: Systematic Review and Meta-Analysis.

Galectins are a family of proteins with an affinity for ß-galactosides that have roles in neuroprotection and neuroinflammation. Several studies indicate that patients with neurodegenerative diseases have alterations in the concentration of galectins in their blood and brain. However, the results of the studies are contradictory; hence, a meta-analysis is performed to clarify whether patients with neurodegenerative diseases have elevated galectin levels compared to healthy individuals. Related publications are obtained from the databases: PubMed, Central-Conchrane, Web of Science database, OVID-EMBASE, Scope, and EBSCO host until February 2022. A pooled standard mean difference (SMD) with a 95% confidence interval (CI) is calculated by fixed-effect or random-effect model analysis. In total, 17 articles are included in the meta-analysis with a total of 905 patients. Patients with neurodegenerative diseases present a higher level of galectin expression compared to healthy individuals (MDS = 0.70, 95% CI 0.28-1.13, p = 0.001). In the subgroup analysis by galectin type, a higher galectin-3 expression is observed in patients with neurodegenerative diseases. Patients with Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALD), and Parkinson's disease (PD) expressed higher levels of galectin-3. Patients with multiple sclerosis (MS) have higher levels of galectin-9. In conclusion, our meta-analysis shows that patients with neurovegetative diseases have higher galectin levels compared to healthy individuals. Galectin levels are associated with the type of disease, sample, detection technique, and region of origin of the patients.

Exposure to a hypercaloric diet produces long lasting changes in motivation.

Changes in motivation have been observed following induction of diet-induced obesity. However, to date, results have been contradictory, some authors reporting an increase in motivation to obtain palatable food, but others observing a decrease. Observed differences might be associated with the length of both the evaluation period and exposure to the diet. Therefore, the aim of this study was to evaluate changes in motivation during 20 weeks of exposure to a hypercaloric diet. Performance of the subjects in a progressive ratio schedule was evaluated before and during the exposure to a high-fat, high-sugar choice diet (HFHSc). A decrease in motivation was observed after 2 weeks of diet exposure, low levels of motivation remained throughout 20 weeks. A comparable decrease in motivation took longer (3 weeks) to develop using chow diet in the control group. Overall, our results suggest that, when changes in motivation are being evaluated, long periods of diet exposure made no further contribution, once motivation decreased, it remained low up to 18 weeks. Exposure to a HFHSc diet is a useful animal model of obesity, since it replicates some pathophysiological and psychological features of human obesity such as an increase in fasting glucose levels, body weight and the weight of adipose tissue.

Synthesis, biological evaluation, molecular docking studies and In-silico ADMET evaluation of pyrazines of pentacyclic triterpenes.

The semisynthesis of novel derivatives of lupeyl palmitate and 3ß-palmitoyloxy-olean-12-ene by introduction of a pyrazine at C-2 / C-3 and modifications of the relatively unexplored C-30 position of lupeol derivatives was conducted, and their cytotoxic and anti-inflammatory activities were evaluated. The derivatives 7, 10 and 11 significantly inhibited the tumor cell lines U251, K562, HCT-15, MCF-7 and SKLU-1, and compounds 7 and 11 were more active (IC50 25.4 ± 2.0 µM and 7.1 ± 0.4 µM, respectively) than the positive control (etoposide (IC50 31.5 ± 2.2 µM) in the tumor line PC-3. Introduction of the pyrazine at C-2 / C-3 in compounds 1 and 2 or modification at C-30 of compound 1 decreased the anti-inflammatory activity in the TPA-induced mouse ear edema. Following the results of the PASS online evaluation of the potential biological activity of the natural compounds and their derivatives, the inhibition of pNF-κB translocation to the prostate cancer (PC-3) cell nucleus was investigated and the binding mode of compounds 7, 10 and 11 with the human NF-κB receptor was explored by a molecular docking study. These derivatives bound directly or close to the amino acids that form the DNA recognition site. The ADMET physicochemical parameters of the fifteen compounds were further analyzed in silico using Molinspiration calculations indicating the potential of compounds 7, 10 and 11 for further investigation.

Role of the Cholinergic Anti-Inflammatory Reflex in Central Nervous System Diseases.

In several central nervous system diseases, it has been reported that inflammation may be related to the etiologic process, therefore, therapeutic strategies are being implemented to control inflammation. As the nervous system and the immune system maintain close bidirectional communication in physiological and pathological conditions, the modulation of inflammation through the cholinergic anti-inflammatory reflex has been proposed. In this review, we summarized the evidence supporting chemical stimulation with cholinergic agonists and vagus nerve stimulation as therapeutic strategies in the treatment of various central nervous system pathologies, and their effect on inflammation.

Effect of Dietary Fatty Acids on MicroRNA Expression Related to Metabolic Disorders and Inflammation in Human and Animal Trials.

Dietary fatty acids (DFAs) play key roles in different metabolic processes in humans and other mammals. DFAs have been considered beneficial for health, particularly polyunsaturated (PUFAs) and monounsaturated fatty acids (MUFAs). Additionally, microRNAs (miRNAs) exert their function on DFA metabolism by modulating gene expression, and have drawn great attention for their potential as biomarkers and therapeutic targets. This review explicitly examined the effects of DFAs on miRNA expression associated with metabolic diseases, such as obesity, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD), as well as inflammation, published in the last ten years. DFAs have been shown to induce and repress miRNA expression associated with metabolic disease and inflammation in different cell types and organisms, both in vivo and in vitro, depending on varying combinations of DFAs, doses, and the duration of treatment. However, studies are limited and heterogeneous in methodology. Additionally, recent studies demonstrated that high fat ketogenic diets, many enriched with saturated fats, do not increase serum saturated fat content in humans, and are not associated with increased inflammation. Thus, these findings shed light on the complexity of novel treatment and DFA interventions for metabolic disease and to maintain health. Further studies are needed to advance molecular therapeutic approaches, including miRNA-based strategies in human health and disease.