Search Results (10)

A body of evidence indicates an association between ultraprocessed foods (UPFs) and health outcomes. Most of it has been obtained through preclinical studies, although a number of observational studies substantiate how a high intake of these products increases the risk of neuropsychiatric disorders, and an increasing amount of dietary intervention studies confirm these findings. The aim of this narrative review is to describe some of the putative mechanisms involved in the deleterious effects of a high intake of UPFs on neuropsychiatric outcomes. A myriad of unhealthy actions may be associated with the consumption of UPFs, and some mechanisms are being discussed. They include UPFs’ high caloric density; their high sugar, sodium, and additives content and low amounts of fiber; and a high palatability that induces overconsumption, acting as obesogens. Moreover, thermal treatment of these foods generates oxidative products such as glycotoxins, lipotoxins, and acrolein, all of which affect the brain. The chemical products act, directly or indirectly, on the gut microbiome and affect the gut–brain axis, causing neuroinflammation, oxidative stress, and neurodegeneration. UPFs also exert various epigenetic effects that affect mental health and might explain the intergenerational inheritance of neuropsychiatric disorders. A diet containing a high proportion of these foods has a low nutritional density, including bioactive protective agents such as antioxidant and anti-inflammatory compounds that promote eubiosis. The evidence shows that UPFs intake affects neuropsychiatric outcomes such as neurodegeneration, cognitive decline, dementia, and mood disorders and reinforces the need to promote a healthy dietary pattern throughout all life stages, thus interfering with the current commercial determinants of health. Full article

Methylglyoxal (MGO), a by-product of glycolysis, plays a significant role in cellular metabolism, particularly under stress conditions. However, MGO is a potent glycotoxin, and its accumulation has been linked to the development of several pathological conditions due to oxidative stress, including diabetes mellitus and neurodegenerative diseases. This paper focuses on the biochemical mechanisms by which MGO contributes to oxidative stress, particularly through the formation of advanced glycation end products (AGEs), its interactions with antioxidant systems, and its involvement in chronic diseases like diabetes, neurodegeneration, and cardiovascular disorders. MGO exerts its effects through multiple signaling pathways, including NF-κB, MAPK, and Nrf2, which induce oxidative stress. Additionally, MGO triggers apoptosis primarily via intrinsic and extrinsic pathways, while endoplasmic reticulum (ER) stress is mediated through PERK-eIF2α and IRE1-JNK signaling. Moreover, the activation of inflammatory pathways, particularly through RAGE and NF-κB, plays a crucial role in the pathogenesis of these conditions. This study points out the connection between oxidative and carbonyl stress due to increased MGO formation, and it should be an incentive to search for a marker that could have prognostic significance or could be a targeted therapeutic intervention in various diseases. Full article

The current study intended to investigate the role of new natural compounds derived from the Sesuvium sesuvioides plant in mitigating symptoms of diabetes and insulin resistance in the diabetic mice model. Anti-advanced glycation activity, insulin, and adiponectin were quantified by enzyme-linked immunosorbent assay (ELISA). Glucose uptake was performed using enzymatic fluorescence assay, and glycogen synthesis was measured using PAS staining. Gene and protein expression was assessed using real time PCR (RT-PCR), and immunoblotting and fluorescent microscopy, respectively. The new flavonoid glycoside eupalitin 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside 1 isolated from S. sesuvioides exhibited anti-AGE activity by reducing human glycated albumin in liver cells. In a diabetic mouse model treated with compound 1, we observed improved glucose tolerance, increased adiponectin levels, and decreased insulin resistance. We also observed alleviated AGEs induced reduction in glucose uptake and restored glycogen synthesis in the compound 1-treated diabetic mice muscles. Exploring the molecular mechanism of action in skeletal muscle tissue of diabetic mice, we found that 1 reduced AGE-induced reactive oxygen species and the inflammatory gene in the muscle of diabetic mice. Additionally, 1 exhibited these effects by reducing the gene and protein expression of receptor for advanced glycation end products (RAGE) and inhibiting protein kinase C (PKC) delta activation. This further led us to demonstrate that compound 1 reduced serine phosphorylation of IRS-1, thereby restoring insulin sensitivity. We conclude that a new flavonoid glycoside from S. sesuvioides could be a therapeutic target for the treatment of symptoms of insulin resistance and diabetes. Full article

Background: Though maternal diabetes effects are well described in the literature, the effects of maternal diabetes in postnatal phases are often overlooked. Diabetic individuals have higher levels of circulating glycotoxins, and there is a positive correlation between maternal-derived glycotoxins and circulating glycotoxins in their progeny. Previous studies evaluated the metabolic effects of high glycotoxin exposure during lactation in adult animals. However, here we focus on the cardiovascular system of juvenile rats. Methods: For this, we used two experimental models: 1. High Methylglyoxal (MG) environment: pregnant Wistar rats were injected with PBS (VEH group) or Methylglyoxal (MG group; 60 mg/kg/day; orally, postnatal day (PND) 3 to PND14). 2. GLO-1 inhibition: pregnant Wistar rats were injected with dimethyl sulfoxide (VEH group) or a GLO-1 inhibitor (BBGC group; 5 mg/kg/day; subcutaneously, PND1–PND5). The offspring were evaluated at PND45. Results: MG offspring presented cardiac dysfunction and subtly worsened vasomotor responses in the presence of perivascular adipose tissue, without morphological alterations. In addition, an endogenous increase in maternal glycotoxins impacts offspring vasomotricity due to impaired redox status. Conclusions: Our data suggest that early glycotoxin exposure led to cardiac and vascular impairments, which may increase the risk for developing cardiovascular diseases later in life. Full article

Obesogenic environments such as Westernized diets, overnutrition, and exposure to glycation during gestation and lactation can alter peripheral neuroendocrine factors in offspring, predisposing for metabolic diseases in adulthood. Thus, we hypothesized that exposure to obesogenic environments during the perinatal period reprograms offspring energy balance mechanisms. Four rat obesogenic models were studied: maternal diet-induced obesity (DIO); early-life obesity induced by postnatal overfeeding; maternal glycation; and postnatal overfeeding combined with maternal glycation. Metabolic parameters, energy expenditure, and storage pathways in visceral adipose tissue (VAT) and the liver were analyzed. Maternal DIO increased VAT lipogenic [NPY receptor-1 (NPY1R), NPY receptor-2 (NPY2R), and ghrelin receptor], but also lipolytic/catabolic mechanisms [dopamine-1 receptor (D1R) and p-AMP-activated protein kinase (AMPK)] in male offspring, while reducing NPY1R in females. Postnatally overfed male animals only exhibited higher NPY2R levels in VAT, while females also presented NPY1R and NPY2R downregulation. Maternal glycation reduces VAT expandability by decreasing NPY2R in overfed animals. Regarding the liver, D1R was decreased in all obesogenic models, while overfeeding induced fat accumulation in both sexes and glycation the inflammatory infiltration. The VAT response to maternal DIO and overfeeding showed a sexual dysmorphism, and exposure to glycotoxins led to a thin-outside-fat-inside phenotype in overfeeding conditions and impaired energy balance, increasing the metabolic risk in adulthood. Full article

Glycotoxins include the group of advanced glycation end-products (AGEs) and their precursors, most of them highly reactive intermediary compounds of sugar metabolism. Glycotoxins and products of the Maillard reaction are present in high concentrations in foods rich in sugars and processed at high temperatures and are often associated with the flavour of the food. Proteins undergoing this type of molecular modification are targets for gut peptidases and may be absorbed into circulation. AGEs are associated with the toxic effects of glucose in diabetic patients, and some studies have shown that they also contribute to metabolically unhealthy obesity and prediabetes development. Restriction of dietary glycotoxins was shown to improve insulin resistance in humans. However, the real contribution of dietary AGEs to such mechanisms is still not understood. This review summarizes the current knowledge about glycotoxin formation from dietary sugars, their digestion throughout the gastrointestinal system, and the mechanisms of their intestinal absorption. Full article

The increased incidence of obesity, diabetes mellitus, aging, and associated comorbidities indicates the interplay between genetic and environmental influences. Several dietary components have been identified to play a role in the pathogenesis of the so-called “modern diseases”, and their complications including advanced glycation end products (AGEs), which are generated during the food preparation and processing. Diet-derived advanced glycation end products (dAGEs) can be absorbed in the gastrointestinal system and contribute to the total body AGEs’ homeostasis, partially excreted in the urine, while a significant amount accumulates to various tissues. Various in vitro, in vivo, and clinical studies support that dAGEs play an important role in health and disease, in a similar way to those endogenously formed. Animal studies using wild type, as well as experimental, animal models have shown that dAGEs contribute significantly to the pathogenesis of various diseases and their complications, and are involved in the changes related to the aging process. In addition, they support that dAGEs’ restriction reduces insulin resistance, oxidative stress, and inflammation; restores immune alterations; and prevents or delays the progression of aging, obesity, diabetes mellitus, and their complications. These data can be extrapolated in humans and strongly support that dAGEs’ restriction should be considered as an alternative therapeutic intervention. Full article

The term glycotoxins includes the group of advanced glycation end-products (AGEs) and their precursors, most of them highly reactive intermediary compounds, such as methylglyoxal (MG). Glycotoxins were initially thought to participate in the development of diabetic complications because of their increased formation from glucose. However, they also form and accumulate in tissues since the early stages of disease, such as metabolically unhealthy obesity and prediabetes. Such accumulation has been suggested to result from dysregulated activity of detoxification systems, such as the glyoxalase system, as well as increased dietary consumption, namely from high-glucose and high-fructose foods processed at high temperatures. Although some studies may have used supraphysiological doses, in vitro systems and animal models have shown glycotoxin-induced insulin resistance. Moreover, dietary glycotoxin restriction was shown to improve insulin resistance in humans and glyoxalase (GLO)-1 upregulation improved insulin sensitivity and metabolic function. This review summarizes the current knowledge about glycotoxin involvement in the development of insulin resistance, the mechanisms involved and the usefulness of GLO-1 modulation, and a possible therapeutic strategy to improve insulin sensitivity. Full article

Women with polycystic ovary syndrome (PCOS) have been reported to have an elevated serum advanced glycation end product (AGE) level. However, the effect of AGEs on the pathophysiological ovarian granulosa cells of PCOS is still unclear. In this study, five indented BSA-derived AGE products were used to evaluate their effect on the function of human granulosa cells. We found that the proliferation of both primary human ovarian granulosa (hGC) cells and human granulosa-like tumor (KGN) cells were inhibited by treatment with these five AGE products. The progesterone secretion level was also reduced in both hGC and KGN cells by treatment with these AGE products through downregulation of LH receptor/cAMP regulatory activity. The granulosa cell layer and serum progesterone level were reduced in rats by treatment with MG-BSA; moreover, an increased number of follicle cysts and an irregular estrous cycle were observed. MG-BSA treatment had a similar effect on the phenotypes of the DHEA-induced PCOS model. Additionally, the insulin resistance and hepatic lesions seen in the DHEA-induced PCOS model were observed in the MG-BSA treatment group. Taken together, we found that AGEs exert a toxic effect on ovarian granulosa cells, ovarian morphology, and the estrous cycle that mimics the DHEA-induced PCOS phenotypes. Full article

Animal venoms represent a valuable source of bioactive peptides that can be derived into useful pharmacological tools, or even innovative drugs. In this way, the venom of Dendroaspis angusticeps (DA), the Eastern Green Mamba, has been intensively studied during recent years. It mainly contains hundreds of large toxins from 6 to 9 kDa, each displaying several disulfide bridges. These toxins are the main target of venom-based studies due to their valuable activities obtained by selectively targeting membrane receptors, such as ion channels or G-protein coupled receptors. This study aims to demonstrate that the knowledge of venom composition is still limited and that animal venoms contain unexpected diversity and surprises. A previous study has shown that Dendroaspis angusticeps venom contains not only a cocktail of classical toxins, but also small glycosylated peptides. Following this work, a deep exploration of DA glycopeptidome by a dual nano liquid chromatography coupled to electrospray ionization mass spectrometry (nanoLC-ESI-MS) and Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) analyses was initiated. This study reveals unsuspected structural diversity of compounds such as 221 glycopeptides, displaying different glycan structures. Sequence alignments underline structural similarities with natriuretic peptides already characterized in Elapidae venoms. Finally, the presence of an S-cysteinylation and hydroxylation of proline on four glycopeptides, never described to date in snake venoms, is also revealed by proteomics and affined by nuclear magnetic resonance (NMR) experiments. Full article