Oxidative stress is important in the pathophysiology of obesity, altering regulatory factors of mitochondrial activity, modifying the concentration of inflammation mediators associated with a large number and size of adipocytes, promoting lipogenesis, stimulating differentiation of preadipocytes to mature adipocytes, and regulating the energy balance in hypothalamic neurons that control appetite. This review discusses the participation of oxidative stress in obesity and the important groups of compounds found in plants with antioxidant properties, which include (a) polyphenols such as phenolic acids, stilbenes, flavonoids (flavonols, flavanols, anthocyanins, flavanones, flavones, flavanonols, and isoflavones), and curcuminoids (b) carotenoids, (c) capsaicinoids and casinoids, (d) isothiocyanates, (e) catechins, and (f) vitamins. Examples are analyzed, such as resveratrol, quercetin, curcumin, ferulic acid, phloretin, green tea, Hibiscus Sabdariffa, and garlic. The antioxidant activities of these compounds depend on their activities as reactive oxygen species (ROS) scavengers and on their capacity to prevent the activation of NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells), and reduce the expression of target genes, including those participating in inflammation. We conclude that natural compounds have therapeutic potential for diseases mediated by oxidative stress, particularly obesity. Controlled and well-designed clinical trials are still necessary to better know the effects of these compounds.

Cardiovascular diseases are being included in the study of developmental origins of health and disease (DOHaD) and essential systemic hypertension has also been added to this field. Epigenetic modifications are one of the main mechanisms leading to early programming of disease. Different environmental factors occurring during critical windows in the early stages of life may leave epigenetic cues, which may be involved in the programming of hypertension when individuals reach adulthood. Such environmental factors include pre-term birth, low weight at birth, altered programming of different organs such as the blood vessels and the kidney, and living in disadvantageous conditions in the programming of hypertension. Mechanisms behind these factors that impact on the programming include undernutrition, oxidative stress, inflammation, emotional stress, and changes in the microbiota. These factors and their underlying causes acting at the vascular level will be discussed in this paper. We also explore the establishment of epigenetic cues that may lead to hypertension at the vascular level such as DNA methylation, histone modifications (methylation and acetylation), and the role of microRNAs in the endothelial cells and blood vessel smooth muscle which participate in hypertension. Since epigenetic changes are reversible, the knowledge of this type of markers could be useful in the field of prevention, diagnosis or epigenetic drugs as a therapeutic approach to hypertension.

Mixtures of resveratrol (RSV) + quercetin (QRC) have antioxidant properties that probably impact on fatty liver in metabolic syndrome (MS) individuals. Here, we study the effects of a mixture of RSV + QRC on oxidative stress (OS) and fatty liver in a rat model of MS. Weanling male Wistar rats were separated into four groups (n = 8): MS rats with 30% sucrose in drinking water plus RSV + QRC (50 and 0.95 mg/kg/day, respectively), MS rats without treatment, control rats (C), and C rats plus RSV + QRC. MS rats had increased systolic blood pressure, triglycerides, insulin levels, insulin resistance index homeostasis model (HOMA), adiponectin, and leptin. The RSV + QRC mixture compensated these variables to C values (p < 0.01) in MS rats. Lipid peroxidation and carbonylation were increased in MS. Total antioxidant capacity and glutathione (GSH) were decreased in MS and compensated in MS plus RVS + QRC rats. Catalase, superoxide dismutase isoforms, peroxidases, glutathione-S-transferase, glutathione reductase, and the expression of Nrf2 were decreased in MS and reversed in MS plus RVS + QRC rats (p < 0.01). In conclusion, the mixture of RSV + QRC has benefic effects on OS in fatty liver in the MS rats through the improvement of the antioxidant capacity and by the over-expression of the master factor Nrf2, which increases the antioxidant enzymes and GSH recycling.

Uncoupling proteins (UCPs) are members of the mitochondrial anion carrier superfamily involved in the control of body temperature and energy balance regulation. They are currently proposed as therapeutic targets for treating obesity and metabolic syndrome (MetS). We studied the gene expression regulation of UCP1, -2, and -3 in abdominal white adipose tissue (WAT) from control and MetS rats treated with two doses of a commercial mixture of resveratrol (RSV) and quercetin (QRC). We found that UCP2 was the predominantly expressed isoform, UCP3 was present at very low levels, and UCP1 was undetectable. The treatment with RSV + QRC did not modify UCP3 levels; however, it significantly increased UCP2 mRNA in control and MetS rats in association with an increase in oleic and linoleic fatty acids. WAT from MetS rats showed a significantly increased expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ when compared to the control group. Furthermore, PPAR-α protein levels were increased by the highest dose of RSV + QRC in the control and MetS groups. PPAR-γ expression was only increased in the control group. We conclude that the RSV + QRC treatment leads to overexpression of UCP2, which is associated with an increase in MUFA and PUFA, which might increase PPAR-α expression.

Oxidative (OS), reductive (RS), and nitrosative (NSS) stresses produce carbonylation, glycation, glutathionylation, sulfhydration, nitration, and nitrosylation reactions. OS, RS, and NSS are interrelated since RS results from an overactivation of antioxidant systems and NSS is the result of the overactivation of the oxidation of nitric oxide (NO). Here, we discuss the general characteristics of the three types of stress and the way by which the reactions they induce (a) damage the DNA structure causing strand breaks or inducing the formation of 8-oxo-d guanosine; (b) modify histones; (c) modify the activities of the enzymes that determine the establishment of epigenetic cues such as DNA methyl transferases, histone methyl transferases, acetyltransferases, and deacetylases; (d) alter DNA reparation enzymes by posttranslational mechanisms; and (e) regulate the activities of intracellular enzymes participating in metabolic reactions and in signaling pathways through posttranslational modifications. Furthermore, the three types of stress may establish new epigenetic marks through these reactions. The development of cardiometabolic disorders in adult life may be programed since early stages of development by epigenetic cues which may be established or modified by OS, RS, and NSS. Therefore, the three types of stress participate importantly in mediating the impact of the early life environment on later health and heritability. Here, we discuss their impact on cardiometabolic diseases. The epigenetic modifications induced by these stresses depend on union and release of chemical residues on a DNA sequence and/or on amino acid residues in proteins, and therefore, they are reversible and potentially treatable.

Nonalcoholic fatty liver disease (NAFLD) is considered a manifestation of metabolic syndrome (MS) and is characterized by the accumulation of triglycerides and a varying degree of hepatic injury, inflammation, and repair. Moreover, peroxisome-proliferator-activated receptors (PPARs) play a critical role in the pathophysiological processes in the liver. There is extensive evidence of the beneficial effect of polyphenols such as resveratrol (RSV) and quercetin (QRC) on the treatment of liver pathology; however, the mechanisms underlying their beneficial effects have not been fully elucidated. In this work, we show that the mechanisms underlying the beneficial effects of RSV and QRC against inflammation in liver damage in our MS model are due to the activation of novel pathways which have not been previously described such as the downregulation of the expression of toll-like receptor 4 (TLR4), neutrophil elastase (NE) and purinergic receptor P2Y2. This downregulation leads to a decrease in apoptosis and hepatic fibrosis with no changes in hepatocyte proliferation. In addition, PPAR alpha and gamma expression were altered in MS but their expression was not affected by the treatment with the natural compounds. The improvement of liver damage by the administration of polyphenols was reflected in the normalization of serum transaminase activities.