Obesity and its associated disorders, such as insulin resistance, dyslipidemia, metabolic inflammation, dysbiosis, and non-alcoholic hepatic steatosis, are involved in several molecular and ...inflammatory mechanisms that alter the metabolism. Food habit changes, such as the quality of fatty acids in the diet, are proposed to treat and prevent these disorders. Some studies demonstrated that saturated fatty acids (SFA) are considered detrimental for treating these disorders. A high fat diet rich in palmitic acid, a SFA, is associated with lower insulin sensitivity and it may also increase atherosclerosis parameters. On the other hand, a high intake of eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids may promote positive effects, especially on triglyceride levels and increased high-density lipoprotein (HDL) levels. Moreover, polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs) are effective at limiting the hepatic steatosis process through a series of biochemical events, such as reducing the markers of non-alcoholic hepatic steatosis, increasing the gene expression of lipid metabolism, decreasing lipogenic activity, and releasing adiponectin. This current review shows that the consumption of unsaturated fatty acids, MUFA, and PUFA, and especially EPA and DHA, which can be applied as food supplements, may promote effects on glucose and lipid metabolism, as well as on metabolic inflammation, gut microbiota, and hepatic metabolism.
Long-term high-fat dietary intake plays a crucial role in the composition of gut microbiota in animal models and human subjects, which affect directly short-chain fatty acid (SCFA) production and ...host health. This review aims to highlight the interplay of fatty acid (FA) intake and gut microbiota composition and its interaction with hosts in health promotion and obesity prevention and its related metabolic dysbiosis. The abundance of the Bacteroidetes/Firmicutes ratio, as Actinobacteria and Proteobacteria species are associated with increased SCFA production, reported high-fat diet rich in medium-chain fatty acids (MCFAs), monounsaturated fatty acids (MUFAs), and n-3 polyunsaturated fatty acids (PUFAs) as well as low-fat diets rich in long-chain fatty acids (LCFAs). SCFAs play a key role in health promotion and prevention and, reduction and reversion of metabolic syndromes in the host. Furthermore, in this review, we discussed the type of fatty acids and their amount, including the administration time and their interplay with gut microbiota and its results about health or several metabolic dysbioses undergone by hosts.
Pseudomonas aeruginosa is an opportunistic ESKAPE pathogen that produces two lectins, LecA and LecB, as part of its large arsenal of virulence factors. Both carbohydrate‐binding proteins are central ...to the initial and later persistent infection processes, i. e. bacterial adhesion and biofilm formation. The biofilm matrix is a major resistance determinant and protects the bacteria against external threats such as the host immune system or antibiotic treatment. Therefore, the development of drugs against the P. aeruginosa biofilm is of particular interest to restore efficacy of antimicrobials. Carbohydrate‐based inhibitors for LecA and LecB were previously shown to efficiently reduce biofilm formations. Here, we report a new approach for inhibiting LecA with synthetic molecules bridging the established carbohydrate‐binding site and a central cavity located between two LecA protomers of the lectin tetramer. Inspired by in silico design, we synthesized various galactosidic LecA inhibitors with aromatic moieties targeting this central pocket. These compounds reached low micromolar affinities, validated in different biophysical assays. Finally, X‐ray diffraction analysis revealed the interactions of this compound class with LecA. This new mode of action paves the way to a novel route towards inhibition of P. aeruginosa biofilms.
A new ligand binding pocket for additional pharmacophores in inhibitors of the bacterial lectin and virulence factor LecA from Pseudomonas aeruginosa was identified and successfully targeted, using a suite of modelling, chemical synthesis, and biophysical analyses. The crystal structure of LecA with one ligand targeting this central pocket was solved, and validated the concept.
Because of the antimicrobial resistance crisis, lectins are considered novel drug targets. Pseudomonas aeruginosa utilizes LecA and LecB in the infection process. Inhibition of both lectins with ...carbohydrate‐derived molecules can reduce biofilm formation to restore antimicrobial susceptibility. Here, we focused on non‐carbohydrate inhibitors for LecA to explore new avenues for lectin inhibition. From a screening cascade we obtained one experimentally confirmed hit, a catechol, belonging to the well‐known PAINS compounds. Rigorous analyses validated electron‐deficient catechols as millimolar LecA inhibitors. The first co‐crystal structure of a non‐carbohydrate inhibitor in complex with a bacterial lectin clearly demonstrates the catechol mimicking the binding of natural glycosides with LecA. Importantly, catechol 3 is the first non‐carbohydrate lectin ligand that binds bacterial and mammalian calcium(II)‐binding lectins, giving rise to this fundamentally new class of glycomimetics.
A screening yields the first non‐carbohydrate small molecules mimicking the interaction of carbohydrates in the binding sites of bacterial lectins. The catechols, known as PAINS, were carefully validated in numerous biophysical assays. A crystal structure in complex with Pseudomonas aeruginosa LecA and NMR analyses with mammalian C‐type lectin Langerin prove the catechol moiety as a general replacement motif for carbohydrates in calcium(II)‐binding lectins.
Neutrophils release fibrous traps of DNA, histones, and granule proteins known as neutrophil extracellular traps (NETs), which contribute to microbicidal killing and have been implicated in ...autoimmunity. The role of NET formation in the host response to nonbacterial pathogens is not well-understood. In this study, we investigated the release of NETs by human neutrophils upon their interaction with Trypanosoma cruzi (Y strain) parasites. Our results showed that human neutrophils stimulated by T. cruzi generate NETs composed of DNA, histones, and elastase. The release occurred in a dose-, time-, and reactive oxygen species-dependent manner to decrease trypomastigote and increase amastigote numbers of the parasites without affecting their viability. NET release was decreased upon blocking with antibodies against Toll-like receptors 2 and 4. In addition, living parasites were not mandatory in the release of NETs induced by T. cruzi, as the same results were obtained when molecules from its soluble extract were tested. Our results increase the understanding of the stimulation of NETs by parasites, particularly T. cruzi. We suggest that contact of T. cruzi with NETs during Chagas's disease can limit infection by affecting the infectivity/pathogenicity of the parasite.
Many populations use medicinal plants as a therapeutic treatment, due to their lower cost and greater access. Among the plant species used for medicinal purposes are those of the genus
. The most ...known species are
,
, and
This review aims to collect data from the literature, predominantly from cell and animal studies, which presents a possible nutraceutical and medicinal potential of the species
for use in metabolic dysfunctions. The fruits and leaves of mulberry are used for therapeutic purposes. For scientific confirmation of these effects, they were studied for laxative properties, antibacterial activity, anti-atherogenic activity, and hepatoprotective function. Furthermore, the genus
is recognized for the treatment and prevention of diabetes mellitus, through its hypoglycemic action. It may also provide health benefits through immunomodulatory, anti-inflammatory, and anti-nociceptive effects. It has been found that the
species have phenolic compounds, flavonoids, and anthocyanins that act as important antioxidants and promote beneficial effects on human health. These phytochemical compounds differ among species. Blackberry (
) are rich in flavonoids, while the white mulberry (
) has low concentrations of flavonoids and anthocyanins. In addition, another important factor is to ensure a complete exemption of toxic risks in the use of medicinal plants for the treatment of diseases. Studies have shown no toxic effects by the administration of extracts of
species. Thus, the mulberry tree presents nutraceutical potential. It is therefore a promising alternative for medicinal products based on medicinal plants.
Metabolic syndrome (MetS) is characterized by interconnected factors related to metabolic disturbances, and is directly related to the occurrence of some diseases such as cardiovascular diseases and ...type 2 diabetes. MetS is described as one or both of insulin resistance and visceral adiposity, considered the initial causes of abnormalities that include hyperglycemia, elevated blood pressure, dyslipidemia, elevated inflammatory markers, and prothrombotic state, as well as polycystic ovarian syndrome in women. Other than in MetS, visceral adiposity and the pro-inflammatory state are also key in the development of non-alcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease in modern society. Both MetS and NAFLD are related to diet and lifestyle, and their treatment may be influenced by dietary pattern changes and the use of certain dietary supplements. This study aimed to review the role of food ingredients and supplements in the management of MetS and NAFLD specifically in human clinical trials. Moreover, bioactive compounds and polyunsaturated fatty acids (PUFAs) may be used as strategies for preventing the onset of and treatment of metabolic disorders, such as MetS and NAFLD, improving the inflammatory state and other comorbidities, such as obesity, dyslipidemias, and cardiovascular diseases (CVD).
Abstract
Differences between the expression of the two alleles of a gene are known as allele-specific expression (ASE), a common event in the transcriptome of mammals. Despite ASE being a source of ...phenotypic variation, its occurrence and effects on genetic prediction of economically relevant traits are still unexplored in bovines. Furthermore, as ASE events are likely driven by cis-regulatory mutations, scanning them throughout the bovine genome represents a significant step to elucidate the mechanisms underlying gene expression regulation. To address this question in a
Bos indicus
population, we built the ASE profile of the skeletal muscle tissue of 190 Nelore steers, using RNA sequencing data and SNPs genotypes from the Illumina BovineHD BeadChip (770 K bp). After quality control, 820 SNPs showed at least one sample with ASE. These SNPs were widespread among all autosomal chromosomes, being 32.01% found in 3′UTR and 31.41% in coding regions. We observed a considerable variation of ASE profile among individuals, which highlighted the need for biological replicates in ASE studies. Functional analysis revealed that ASE genes play critical biological functions in the development and maintenance of muscle tissue. Additionally, some of these genes were previously reported as associated with beef production and quality traits in livestock, thus indicating a possible source of bias on genomic predictions for these traits.
Consumption of omega-3 (n-3) polyunsaturated fatty acids (PUFA) is related to improvement in the inflammatory response associated with decreases in metabolic disorders of obesity, such as low-grade ...inflammation and hepatic steatosis. Linseed (
) oil is a primary source of n-3 fatty acids (FAs) of plant origin, particularly α-linolenic acid, and provides an alternative for the ingestion of n-3 PUFA by persons allergic to, or wishing to avoid, animal sources. In our study, we evaluated the effect of the consumption of different lipidic sources on metabolic and inflammatory parameters in Wistar rats. We split 56 male rats into four groups that were fed for 60 days with the following diets: sesame oil, (SO,
), linseed oil (LO), SO + LO (SLO), and a control group (CG) fed with animal fat. Our results reveal that the use of LO or SLO produced improvements in the hepatic tissue, such as lower values of aspartate aminotransferase, liver weight, and hepatic steatosis. LO and SLO reduced the weight of visceral fats, weight gain, and mediated the inflammation through a decrease in interleukin (IL)-6 and increase in IL-10. Though we did not detect any significant differences in the intestine histology and the purinergic system enzymes, the consumption of α-linolenic acid appears to contribute to the inflammatory and hepatic modulation of animals compared with a diet rich in saturated FAs and or unbalanced in n-6/n-3 PUFAs, inferring possible use in treatment of metabolic disorders associated with obesity and cardiovascular diseases.
Obesity, in conjunction with other metabolic disorders such as insulin resistance and dyslipidemia, is a feature of metabolic syndrome which is characterized by a pro-inflammatory state and increased ...oxidative stress. Therefore, antioxidant foods are proposed to prevent and treat these disorders. Medicinal plants are one of the main strategies in this regard. Guavira, a Brazilian Cerrado plant, contains different bioactive compounds with a high antioxidant capacity and without clinical or reproductive toxicity effects. Though there are different varieties of guavira, the principal Brazilian Cerrado guaviras demonstrated hypoglycemic, anti-inflammatory, and hypocholesterolemic actions. There is also a potential antiplatelet agent in
, while
displayed hypocholesterolemic actions in animal models and human clinical trials. On the other hand, even with a lack of studies related to
, it demonstrated anti-inflammatory effects and an antioxidant capacity in in vitro studies. Despite the fact that most of the studies were not performed to evaluate pathological conditions specific to obese animal models or obese subjects, guavira demonstrated effects in metabolic disorders that are commonly related to the obesity context, such as cardiovascular disturbances and hyperglycemia status. This suggests that guavira is a potential therapeutic approach to obesity-induced metabolic syndrome.
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