Dietary Strategies for Management of Metabolic Syndrome: Role of Gut Microbiota Metabolites

Metabolic syndrome (MetS) is a complex pathophysiological state with incidence similar to that of a global epidemic and represents a risk factor for the onset of chronic non-communicable degenerative diseases (NCDDs), including cardiovascular disease (CVD), type 2 diabetes mellitus, chronic kidney disease, and some types of cancer. A plethora of literature data suggest the potential role of gut microbiota in interfering with the host metabolism, thus influencing several MetS risk factors. Perturbation of the gut microbiota's composition and activity, a condition known as dysbiosis, is involved in the etiopathogenesis of multiple chronic diseases. Recent studies have shown that some micro-organism-derived metabolites (including trimethylamine N-oxide (TMAO), lipopolysaccharide (LPS) of Gram-negative bacteria, indoxyl sulfate and p-cresol sulfate) induce subclinical inflammatory processes involved in MetS. Gut microbiota's taxonomic species or abundance are modified by many factors, including diet, lifestyle and medications. The main purpose of this review is to highlight the correlation between different dietary strategies and changes in gut microbiota metabolites. We mainly focus on the validity/inadequacy of specific dietary patterns to reduce inflammatory processes, including leaky gut and subsequent endotoxemia. We also describe the chance of probiotic supplementation to interact with the immune system and limit negative consequences associated with MetS

O-GlcNAcylation and oxidation of proteins: is signalling in the cardiovascular system becoming sweeter?

O-GlcNAcylation is an unusual form of protein glycosylation, where a single-sugar [GlcNAc (N-acetylglucosamine)] is added (via β-attachment) to the hydroxyl moiety of serine and threonine residues of nuclear and cytoplasmic proteins. A complex and extensive interplay exists between O-GlcNAcylation and phosphorylation. Many phosphorylation sites are also known glycosylation sites, and this reciprocal occupancy may produce different activities or alter the stability in a target protein. The interplay between these two post-translational modifications is not always reciprocal, as some proteins can be concomitantly phosphorylated and O-GlcNAcylated, and the adjacent phosphorylation or O-GlcNAcylation can regulate the addition of either moiety. Increased cardiovascular production of ROS (reactive oxygen species), termed oxidative stress, has been consistently reported in various chronic diseases and in conditions where O-GlcNAcylation has been implicated as a contributing mechanism for the associated organ injury/protection (for example, diabetes, Alzheimer's disease, arterial hypertension, aging and ischaemia). In the present review, we will briefly comment on general aspects of O-GlcNAcylation and provide an overview of what has been reported for this post-translational modification in the cardiovascular system. We will then specifically address whether signalling molecules involved in redox signalling can be modified by O-GlcNAc (O-linked GlcNAc) and will discuss the critical interplay between O-GlcNAcylation and ROS generation. Experimental evidence indicates that the interactions between O-GlcNAcylation and oxidation of proteins are important not only for cell regulation in physiological conditions, but also under pathological states where the interplay may become dysfunctional and thereby exacerbate cellular injury

Removal of urea in a wearable dialysis device: a reappraisal of electro-oxidation

A major challenge for a wearable dialysis device is removal of urea, as urea is difficult to adsorb while daily production is very high. Electro‐oxidation (EO) seems attractive because electrodes are durable, small, and inexpensive. We studied the efficacy of urea oxidation, generation of chlorine by‐products, and their removal by activated carbon (AC). EO units were designed. Three electrode materials (platinum, ruthenium oxide, and graphite) were compared in single pass experiments using urea in saline solution. Chlorine removal by AC in series with EO by graphite electrodes was tested. Finally, urea‐spiked bovine blood was dialyzed and dialysate was recirculated in a dialysate circuit with AC in series with an EO unit containing graphite electrodes. Platinum electrodes degraded more urea (21 ± 2 mmol/h) than ruthenium oxide (13 ± 2 mmol/h) or graphite electrodes (13 ± 1 mmol/h). Chlorine generation was much lower with graphite (13 ± 4 mg/h) than with platinum (231 ± 22 mg/h) or ruthenium oxide electrodes (129 ± 12 mg/h). Platinum and ruthenium oxide electrodes released platinum (4.1 [3.9–8.1] umol/h) and ruthenium (83 [77–107] nmol/h), respectively. AC potently reduced dialysate chlorine levels to <0.10 mg/L. Urea was removed from blood by EO at constant rate (9.5 ± 1.0 mmol/h). EO by graphite electrodes combined with AC shows promising urea removal and chlorine release complying with Association for the Advancement of Medical Instrumentation standards, and may be worth further exploring for dialysate regeneration in a wearable system