0000000000671968
AUTHOR
Sandra López-domènech
Role of Endoplasmic Reticulum and Oxidative Stress Parameters in the Pathophysiology of Disease-Related Malnutrition in Leukocytes of an Outpatient Population
Cellular pathways such as inflammation or oxidative stress are the cause and triggers of disease-related malnutrition (DRM), but the influence of these markers on endoplasmic reticulum (ER) stress is unknown. The objective of this study was to analyze the relationship between mitochondrial function and ER stress parameters in a DRM population. The study population was composed of 82 outpatient subjects, of whom 45 were diagnosed with DRM and 37 were confirmed to be normonourished according to the American Society for Parenteral and Enteral Nutrition ASPEN criteria. We evaluated anthropometrical and biochemical parameters, pro-inflammatory cytokines in serum. Oxidative and ER stress markers …
Malnutrition impairs mitochondrial function and leukocyte activation
Abstract Background The aim of this study was to evaluate markers of inflammation, oxidative stress and endothelial function in a disease-related malnutrition (DRM) outpatient population. Methods For this cross-sectional study, a total of 83 subjects were included and clustered in 3 groups: 34 with normonutrition (NN), 21 with DRM without inflammation (DRM-I) and 28 with DRM and inflammation (DRM + I). Nutritional diagnosis was conducted for all subjects according to ASPEN. Biochemical parameters, proinflammatory cytokines, reactive oxygen species production, glutathione, mitochondrial membrane potential, oxygen consumption, adhesion molecules and leukocyte-endothelium interactions were eva…
Moderate weight loss attenuates chronic endoplasmic reticulum stress and mitochondrial dysfunction in human obesity
Abstract Objective In obese patients undergoing caloric restriction, there are several potential mechanisms involved in the improvement of metabolic outcomes. The present study further explores whether caloric restriction can modulate endoplasmic reticulum (ER) stress and mitochondrial function, as both are known to be mechanisms underlying inflammation and insulin resistance (IR) during obesity. Methods A total of 64 obese patients with BMI ≥35 kg/m2 underwent a dietary program consisting of 6 weeks of a very-low-calorie diet followed by 18 weeks of low-calorie diet. We evaluated changes in the metabolic and inflammatory markers -TNFα, hsCRP, complement component 3 (C3c), and retinol bindi…
Effect of Roux-en-Y Bariatric Bypass Surgery on Subclinical Atherosclerosis and Oxidative Stress Markers in Leukocytes of Obese Patients: A One-Year Follow-Up Study
Little is known about the mechanisms underlying the cardioprotective effect of Roux en-Y gastric bypass (RYGB) surgery. Therefore, the aim of the present study was to investigate whether weight loss associated with RYGB improves the oxidative status of leukocytes and ameliorates subclinical atherosclerotic markers. This is an interventional study of 57 obese subjects who underwent RYGB surgery. We determined biochemical parameters and qualitative analysis of cholesterol, leukocyte and systemic oxidative stress markers &mdash
Are Mitochondrial Fusion and Fission Impaired in Leukocytes of Type 2 Diabetic Patients?
Mitochondrial fusion/fission alterations have been evaluated in different tissues of type 2 diabetic (T2D) patients. However, it is not known whether mitochondrial dynamics is disturbed in the leukocytes of T2D patients and whether glycemic control affects its regulation. Anthropometric and metabolic parameters in 91 T2D patients (48 with glycated hemoglobin [HbA1c]6.5% and 43 with HbA1c6.5%) were characteristic of the disease when compared with 78 control subjects. We observed increased reactive oxygen species production in leukocytes from diabetic patients, together with a reduced mitochondrial oxygen consumption rate, especially in poorly controlled patients. Mitochondrial fusion was red…
Testosterone administration increases leukocyte-endothelium interactions and inflammation in transgender men
Objective To evaluate the effect of testosterone treatment on metabolic and inflammation parameters and leukocyte-endothelium interactions in transgender men (TGM). Design Prospective observational study. Setting University hospital. Patient(s) One hundred fifty-seven TGM. Intervention(s) Administration of testosterone undecanoate (1,000 mg, intramuscular) every 12 weeks. Main Outcome Measure(s) Endocrine parameters, adhesion molecules (vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, and E-selectin), proinflammatory cytokines interleukin-6, and tumor necrosis factor alpha were evaluated in serum before and after treatment using Luminex’s xMAP technology. In additi…
Mitochondrial Alterations and Enhanced Human Leukocyte/Endothelial Cell Interactions in Type 1 Diabetes
Type 1 diabetes has been associated with oxidative stress. This study evaluates the rates of oxidative stress, mitochondrial function, leukocyte&ndash
Metformin modulates human leukocyte/endothelial cell interactions and proinflammatory cytokines in polycystic ovary syndrome patients
Abstract Objective We aim to assess the effect of metformin treatment on metabolic parameters, endothelial function and inflammatory markers in polycystic ovary syndrome (PCOS) subjects. Methods The study population consisted of 40 reproductive-age women with PCOS, who underwent treatment with metformin during a 12-week period, and their corresponding matched controls (n = 44). We evaluated endocrinological parameters, adhesion molecules (vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule 1 (ICAM-1) and E-selectin) and proinflammatory cytokines (interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα)) in serum. In addition, interactions between human umbili…
MOESM1 of Malnutrition impairs mitochondrial function and leukocyte activation
Additional file 1: Figure S1. Flow Chart of the number of subjects throughout the study.
Does Empagliflozin Modulate Leukocyte–Endothelium Interactions, Oxidative Stress, and Inflammation in Type 2 Diabetes?
Sodium-glucose co-transporter 2 inhibitors (iSGLT2) have been linked to cardiovascular risk reduction in patients with type 2 diabetes (T2D). However, their underlying molecular mechanisms remain unclear. This study aimed to evaluate the effects of empagliflozin, a novel potent and selective iSGLT-2, on anthropometric and endocrine parameters, leukocyte–endothelium interactions, adhesion molecules, ROS production, and NFkB-p65 transcription factor expression. According to standard clinical protocols, sixteen T2D patients receiving 10 mg/day of empagliflozin were followed-up for 24 weeks. Anthropometric and analytical measurements were performed at baseline, 12 weeks, and 24 weeks. Interacti…
Chronic periodontitis impairs polymorphonuclear leucocyte-endothelium cell interactions and oxidative stress in humans.
Aim To evaluate the relationship between oxidative stress parameters in polymorphonuclear leucocytes (PMNs) and PMN-endothelial cell interactions in patients with chronic periodontitis (CP) according to different degrees of severity of the disease. Materials and methods For this cross-sectional study, 182 subjects were divided into four groups according to degree of CP: without CP (n = 37), mild CP (n = 59), moderate CP (n = 51), and severe CP (n = 35). We determined anthropometric and biochemical variables, periodontal parameters, inflammatory markers, oxidative stress parameters (superoxide and mitochondrial membrane potential), and PMN-endothelium cell interactions (rolling flux, velocit…
Association between Proinflammatory Markers, Leukocyte–Endothelium Interactions, and Carotid Intima–Media Thickness in Type 2 Diabetes: Role of Glycemic Control
Glycated hemoglobin monitorization could be a tool for maintaining type 2 diabetes (T2D) under control and delaying the appearance of cardiovascular events. This cross-sectional study was designed to assess the role of glycemic control in modulating early-stage markers of cardiovascular complications. One hundred and eight healthy controls and 161 type 2 diabetic patients were recruited and distributed according to their glycemic control, setting the threshold at 6.5% (good control). Biochemical and anthropometrical parameters were registered during the initial visit, and peripheral blood was extracted to obtain polymorphonuclear cells and analyze inflammatory markers, adhesion molecules, l…
Relationship Between Oxidative Stress, ER Stress, and Inflammation in Type 2 Diabetes: The Battle Continues
Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation. Endoplasmic reticulum (ER) stress plays an important role in oxidative stress, as it is also a source of ROS. The tight interconnection between both organelles through mitochondrial-associated membranes (MAM…
Levels of serum retinol-binding protein 4 before and after non-surgical periodontal treatment in lean and obese subjects: An interventional study
AimWe aimed to evaluate serum RBP4 levels before and after periodontal therapy in lean and obese subjects with chronic periodontitis (CP) in order to determine its possible association with periodontitis. Materials and MethodsThis is an interventional study for which a total of 112 lean and 119 obese subjects were recruited. Patients with CP were evaluated before and after three months of non-surgical periodontal treatment. Periodontal, anthropometric, biochemical parameters and serum levels of TNF-, IL-6, hs-CRP and RBP4 were assessed. ResultsSerum RBP4 levels were associated with an increased probability of periodontitis (OR=1.60; 95% CI: 1.02-2.50), showing patients with CP to have highe…
Pinitol alleviates systemic inflammatory cytokines in human obesity by a mechanism involving unfolded protein response and sirtuin 1
Summary Background & aims It is known that pinitol acts as a mediator of the insulin-signaling pathway, though little is known about its anti-inflammatory effect in human obesity. Therefore, this study aimed to evaluate the effect of pinitol on peripheral blood mononuclear cells (PBMCs) and visceral (VAT) and subcutaneous adipose tissues (SAT), focusing on the involvement of endoplasmic reticulum (ER) stress and sirtuin 1 (SIRT1). Methods In the intervention study, thirteen obese subjects consumed a pinitol-enriched beverage (PEB) for 12 weeks. In the ex vivo study, a biopsy of VAT and SAT was removed from thirty-four obese patients and incubated with D-pinitol for 48 h. Results The consump…
Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin.
Obesity is a low-grade inflammatory condition affecting a range of individuals, from metabolically healthy obese (MHO) subjects to type 2 diabetes (T2D) patients. Metformin has been shown to display anti-inflammatory properties, though the underlying molecular mechanisms are unclear. To study whether the effects of metformin are mediated by changes in the inflammasome complex and autophagy in visceral adipose tissue (VAT) of obese patients, a biopsy of VAT was obtained from a total of 68 obese patients undergoing gastric bypass surgery. The patients were clustered into two groups: MHO patients and T2D patients treated with metformin. Patients treated with metformin showed decreased levels o…
Oxidative and endoplasmic reticulum stress is impaired in leukocytes from metabolically unhealthy vs healthy obese individuals.
BACKGROUND: Oxidative stress and inflammation are related to obesity, but the influence of metabolic disturbances on these parameters and their relationship with endoplasmic reticulum (ER) stress is unknown. Therefore, this study was performed to evaluate whether metabolic profile influences ER and oxidative stress in an obese population with/without comorbidities. SUBJECTS AND METHODS: A total of 113 obese patients were enrolled in the study; 29 were metabolically healthy (MHO), 53 were metabolically abnormal (MAO) and 31 had type 2 diabetes (MADO). We assessed metabolic parameters, proinflammatory cytokines (TNF alpha and IL-6), mitochondrial and total reactive oxygen species (ROS) produc…
Dietary therapy and non-surgical periodontal treatment in obese patients with chronic periodontitis.
Aim The effect of dietary weight loss intervention on periodontal therapy is unknown. Therefore, we aimed to evaluate whether weight loss improves the response of obese subjects to non-surgical periodontal treatment. Materials and methods This interventional study in obese patients was conducted at the University Hospital Dr. Peset (Valencia, Spain). Patients were divided into two groups with and without dietary therapy. All participants received non-surgical periodontal treatment. Periodontal, anthropometric and biochemical parameters were assessed at baseline and 12 weeks. Results A total of 78 patients were re-evaluated after intervention. All periodontal parameters improved in both grou…
Effect of consumption of a carob pod inositol-enriched beverage on insulin sensitivity and inflammation in middle-aged prediabetic subjects.
This study assessed the effects of an inositol-enriched beverage (IEB) on blood glucose levels and inflammation status in subjects with an impaired fasting glucose (IFG) state according to body mass index (BMI). This was a 12 week, double-blind, randomized, controlled trial employing forty-four IFG subjects (fasting glucose levels 100-125 mg dl-1) that were divided into two intervention groups: one receiving a IEB (n = 24) containing mainly pinitol (2.0 g twice a day), and the other a sweetened beverage based on sucrose (SB; n = 20). Anthropometric and biochemical measurements, postprandial and fasting nocturnal glycaemia (continuous glucose monitoring system), and inflammatory parameters (…
Does Metformin Protect Diabetic Patients from Oxidative Stress and Leukocyte-Endothelium Interactions?
Since metformin can exert beneficial vascular effects, we aimed at studying its effect on reactive oxygen species (ROS) production, antioxidant enzyme expression, levels of adhesion molecules, and leukocyte-endothelium interactions in the leukocytes from type 2 diabetic (T2D) patients. The study was carried out in 72 T2D patients (41 of whom were treated with metformin for at least 12 months at a dose of 1700 mg per day), and in 40 sex- and age-matched control subjects. Leukocytes from T2D patients exhibited enhanced levels of mitochondrial ROS and decreased mRNA levels of glutathione peroxidase 1 (gpx1) and sirtuin 3 (sirt3) with respect to controls, whereas metformin was shown to revert t…
The Mitochondrial Antioxidant SS-31 Modulates Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Type 2 Diabetes
Mitochondrial dysfunction has been shown to play a central role in the pathophysiology of type 2 diabetes (T2D), and mitochondria-targeted agents such as SS-31 are emerging as a promising strategy for its treatment. We aimed to study the effects of SS-31 on leukocytes from T2D patients by evaluating oxidative stress, endoplasmic reticulum (ER) stress and autophagy. Sixty-one T2D patients and 53 controls were included. Anthropometric and analytical measurements were performed. We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2&alpha
Obesity impairs leukocyte‐endothelium cell interactions and oxidative stress in humans
Background:To evaluate the relationship between leukocyte‐endothelial cellinteractions and oxidative stress parameters in non‐diabetic patients with differentgrades of obesity.Material and methods:For this cross‐sectional study, 225 subjects wererecruited from January 1, 2014 to December 31, 2016 and divided into groupsaccording to BMI (40 kg/m²). We determined clin-ical parameters, systemic inflammatory markers, soluble cellular adhesion mole-cules, leukocyte‐endothelium cell interactions—rolling flux, velocity and adhesion—, oxidative stress parameters—total ROS, total superoxide, glutathione—andmitochondrial membrane potential in leukocytes.Results:We verified that HOMA‐IR and hsCRP incr…
Relationship between PMN-endothelium interactions, ROS production and Beclin-1 in type 2 diabetes.
Type 2 diabetes is closely related to oxidative stress and cardiovascular diseases. In this study, we hypothesized that polymorphonuclear leukocytes (PMN)-endothelium interactions and autophagy are associated. We evaluated PMN-endothelial interactions, ROS production and autophagy parameters in 47 type 2 diabetic patients and 57 control subjects. PMNs from type 2 diabetic patients exhibited slower rolling velocity (p < 0.001), higher rolling flux (p < 0.001) and adhesion (p < 0.001) in parallel to higher levels of total (p < 0.05) and mitochondrial ROS (p < 0.05). When the protein expression of autophagy markers was analysed, an increase of Beclin-1 (p < 0.05), LC3I (p < 0.05), LC3II (p < 0…
Mitochondrial DNA Haplogroup JT is Related to Impaired Glycaemic Control and Renal Function in Type 2 Diabetic Patients
The association between mitochondrial DNA (mtDNA) haplogroup and risk of type 2 diabetes (T2D) is undetermined and controversial. This study aims to evaluate the impact of the main mtDNA haplogroups on glycaemic control and renal function in a Spanish population of 303 T2D patients and 153 healthy controls. Anthropometrical and metabolic parameters were assessed and mtDNA haplogroup was determined in each individual. Distribution of the different haplogroups was similar in diabetic and healthy populations and, as expected, T2D patients showed poorer glycaemic control and renal function than controls. T2D patients belonging to the JT haplogroup (polymorphism m.4216T>
Downregulation of miR-31 in Diabetic Nephropathy and its Relationship with Inflammation
Background/Aims: There is a lack of reliable biological markers for the early diagnosis of diabetic nephropathy (DN) during type 2 diabetes. In this pilot study we aim to assess whether miR-31 levels are modulated by the presence of DN and whether the expression of this miRNA is related to leukocyte-endothelial interactions and inflammation. Methods: Thirty-one T2D patients were enrolled in this pilot study; 18 with no diabetic complications and 13 with diabetic nephropathy. 24 non-diabetic subjects and 13 T2D patients with retinopathy (absent of other complications) were included to test the specificity of miR-31. Following anthropometric and biochemical evaluation, serum miR-31 levels wer…
Why mammalian wound-healing researchers may wish to turn to Drosophila as a model.
Wound healing is an essential and complex biological process that allows tissue continuity and functioning to be restored after injury. Understanding the molecular and cellular mechanisms underlying wound repair is essential to develop new therapies that could be useful not only to accelerate the normal healing process but also to treat healing pathologies that appear as a consequence of improper wound resolution. Numerous models have been developed to study wound healing both in vitro and in vivo. In vitro models have been useful to study some steps of epithelial repair. However, the development of effective treatments for wound healing is still required, and this could mainly be achieved …
Is Autophagy Altered in the Leukocytes of Type 2 Diabetic Patients?
It is unknown whether autophagy is altered in the leukocytes of type 2 diabetes (T2D) patients and whether oxidative and endoplasmic reticulum (ER) stresses regulate this mechanism. We studied anthropometric and metabolic parameters and evaluated oxidative stress, chromatin condensation, ER stress, and autophagy parameters in leukocytes of 103 T2D patients versus 109 sex- and age-matched controls. Patients showed increases in glucose, insulin, homeostasis model assessment of insulin resistance, and glycated hemoglobin (HbA1c) compared with controls (p < 0.001). Leukocytes displayed enhanced total and mitochondrial reactive oxygen species (ROS), reduced mitochondrial mass, and increased chro…
The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes
AbstractThere is growing focus on mitochondrial impairment and cardiovascular diseases (CVD) in type 2 diabetes (T2D), and the development of novel therapeutic strategies in this context. It is unknown whether mitochondrial-targeting antioxidants such as SS-31 protect sufficiently against oxidative damage in diabetes. We aimed to evaluate if SS-31 modulates SIRT1 levels and ameliorates leukocyte-endothelium interactions, oxidative stress and inflammation in T2D patients. Anthropometric and metabolic parameters were studied in 51 T2D patients and 57 controls. Production of mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential, glutathione content, leukocyte-endotheliu…
Effect of Non-Surgical Periodontal Treatment on Oxidative Stress Markers in Leukocytes and Their Interaction with the Endothelium in Obese Subjects with Periodontitis: A Pilot Study
Aim: The primary objective of this pilot study was to evaluate the effect of non-surgical periodontal treatment. The secondary aim was to evaluate the effect of dietary therapy on both parameters of oxidative stress in leukocytes and leukocyte-endothelial cell interactions in an obese population. Methods: This was a pilot study with a before-and-after design. Forty-nine obese subjects with periodontitis were randomized by means of the minimization method and assigned to one of two groups, one of which underwent dietary therapy while the other did not. All the subjects underwent non-surgical periodontal treatment. We determined periodontal, inflammatory and oxidative stress parameters&mdash