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BackgroundThe relationship between caloric restriction-mediated weight loss and the generation of ROS and its effects on atherosclerotic markers in obesity is not fully understood. Therefore, we set out to investigate whether dietary weight loss intervention improves markers of oxidative stress in leukocytes and subclinical parameters of atherosclerosis.Subjects and MethodsThis was an interventional study of 59 obese subjects (BMI > 35 kg/m2) who underwent 6 months of dietary therapy, including a 6-week very-low-calorie diet (VLCD) followed by an 18-week low-calorie diet (LCD). We determined clinical parameters, inflammatory markers—hsCRP, TNFα and NFκB –, oxidative stress parameters—total superoxide, glutathione, catalase activity and protein carbonyl groups–, soluble cellular adhesion molecules—sICAM, sP-selectin, sPSGL-1 –, myeloperoxidase (MPO), leukocyte-endothelium cell interactions—rolling flux, velocity and adhesion—and LDL subfractions, before and after the dietary intervention.ResultsAfter losing weight, an improvement was observed in the patients’ anthropometric, blood pressure and metabolic parameters, and was associated with reduced inflammatory response (hsCRP, TNFα and NFκB). Oxidative stress parameters improved, since superoxide production and protein carbonyl content were reduced and antioxidant systems were enhanced. In addition, a significant reduction of subclinical markers of atherosclerosis—small and dense LDL particles, MPO, sP-selectin and leukocyte adhesion—and an increase in soluble PSGL-1 were reported.ConclusionsOur findings reveal that the improvement of subclinical atherosclerotic markers after dietary weight loss intervention is associated with a reduction of oxidative stress in leukocytes and inflammatory pathways, suggesting that these are the underlying mechanisms responsible for the reduced risk of cardiovascular disease in obese subjects after losing weight.

Cardiovascular diseases and oxidative stress are related to polycystic ovary syndrome (PCOS) and insulin resistance (IR). We have evaluated the relationship between myeloperoxidase (MPO) and leukocyte activation in PCOS patients according to homeostatic model assessment of IR (HOMA-IR), and have explored a possible correlation between these factors and endocrine and inflammatory parameters. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 101 PCOS subjects and 105 control subjects. We divided PCOS subjects into PCOS non-IR (HOMA-IR<2.5) and PCOS IR (HOMA-IR>2.5). Metabolic and anthropometric parameters, total and mitochondrial reactive oxygen species (ROS) production, MPO levels, interactions between human umbilical vein endothelial cells and leukocytes, adhesion molecules (E-selectin, ICAM-1 and VCAM-1) and proinflammatory cytokines (IL-6 and TNF-α) were evaluated. Oxidative stress was observed in PCOS patients, in whom there was an increase in total and mitochondrial ROS production and MPO levels. Enhanced rolling flux and adhesion, and a decrease in polymorphonuclear cell rolling velocity were also detected in PCOS subjects. Increases in IL-6 and TNF-α and adhesion molecules (E-selectin, ICAM-1 and VCAM-1) were also observed, particularly in the PCOS IR group, providing evidence that inflammation and oxidative stress are related in PCOS patients. HOMA-IR was positively correlated with hsCRP (p<0.001, r = 0.304), ROS production (p<0.01, r = 0.593), leukocyte rolling flux (p<0.05, r = 0.446), E-selectin (p<0.01, r = 0.436) and IL-6 (p<0.001, r = 0.443). The results show an increase in the rate of ROS and MPO levels in PCOS patients in general, and particularly in those with IR. Inflammation in PCOS induces leukocyte-endothelium interactions and a simultaneous increase in IL-6, TNF-α, E-selectin, ICAM-1 and VCAM-1. These conditions are aggravated by the presence of IR.

Obesity and its related disorders, such as diabetes and cardiovascular risk, represent an emerging global health issue. Even though genetic factors seem to be the primary actors in the development and progression of these diseases, dietary choices also appear to be of crucial importance. A healthy diet combined with physical activity have been shown to ameliorate glycaemic levels and insulin sensitivity, reduce body weight and the risk of chronic diseases, and contribute to an overall improvement in quality of life. Among nutrients, phytosterols have become the focus of growing attention as novel functional foods in the management of metabolic disorders. Phytosterols are natural plant compounds belonging to the triterpene family and are structurally similar to cholesterol. They are known for their cholesterol-lowering effects, anti-inflammatory and antioxidant properties, and the benefits they offer to the immune system. The present review aims to provide an overview of these bioactive compounds and their therapeutic potential in the fields of obesity and metabolic disorders, with special attention given to oxidative stress, inflammatory status, and gut dysbiosis, all common features of the aforementioned diseases.

Background Cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) are major contributors to global morbidity and mortality, shaped by social, environmental and behavioural determinants. Assessing the spatial distribution and socio-economic stratification of these conditions at fine geographic scales can inform place-based public health strategies. This study characterises the spatial patterns, socioeconomic gradients and temporal evolution of diagnosed CVD and T2DM incidence in the urban context of Valencia, Spain, for adults aged ≥ 40 years from 2015 to 2022. Methods We conducted a retrospective, registry-based, open cohort study using routinely collected clinical data linked to population registries across 26 postcodes in Valencia. Incident CVD and T2DM cases were identified using prespecified ICD-9/10-CM codes. Person-years at risk were aggregated annually by census tract, sex and age. Age- and sex-adjusted incidence rates were derived by direct standardisation. Spatial clustering was evaluated using global Moran’s I with first-order queen contiguity weights. Socioeconomic gradients were assessed via tract-level mean income per unit of consumption, both categorically (quartiles) and continuously using generalised additive models to analyse non-linear associations. Results Over 3.4 million person-years, we identified 19,902 first CVD events and 27,245 T2DM diagnoses, corresponding to crude incidence rates of 5.85 and 8.55 per 1,000 person-years, respectively. Age- and sex-adjusted incidence exhibited inverse gradients across income quartiles for both outcomes, steeper for T2DM. Spatial autocorrelation was significant for all incidence surfaces ( p  < 0.001), markedly stronger for T2DM ( I  = 0.462) than for CVD ( I  = 0.174). Non-linear modelling revealed pronounced socioeconomic gradients at lower income levels, particularly for T2DM. Conclusions In Valencia, diagnosed CVD and T2DM incidence show clear socioeconomic and spatial inequalities, with pronounced clustering and steep income-related gradients for T2DM. These results underscore the importance of geographically targeted interventions to mitigate cardiometabolic health disparities.

There 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-endothelium interactions, NFκB-p65, TNFα and SIRT1 levels was measured in leukocytes treated or not with SS-31. We observed increased mitochondrial ROS production that was restored by SS-31 treatment. SS-31 also increased mitochondrial membrane potential, glutathione content, SIRT1 levels and leukocyte rolling velocity and reduced rolling flux and adhesion in T2D patients. NFκB-p65 and TNFα, which were enhanced in diabetic patients, were also reduced by SS-31 treatment. Our results reveal that SS-31 exerts beneficial effects on the leukocytes of T2D patients by reducing oxidative stress, leukocyte-endothelium interactions, NFκB and TNFα and by increasing SIRT1 levels. These actions support its use as a potential agent against CVD risk.

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 were assessed by Real Time-PCR. Leukocyte-endothelial interactions were evaluated by a parallel flow chamber in vitro model. Serum TNFα, IL-6 and ICAM-1 levels were determined by XMAP-technology in a flow cytometry-based Luminex 200 instrument. Results: Serum miR-31 levels were similar between control and T2D subjects. However, T2D patients with DN displayed reduced levels of miR-31 with respect to patients without complications. This decrease in miR-31 was more pronounced in patients with macroalbuminuria than in those with microalbuminuria and was specific for DN, since patients with retinopathy displayed unaltered miR-31 levels. The presence of DN involved a lower leukocyte rolling velocity and an increased rolling flux and adhesion. miR-31 levels were positively correlated with leukocyte rolling velocity and negatively associated to leukocyte adhesion, TNFα, IL-6 and ICAM-1 levels. Conclusion: Serum miR-31 may be a biomarker for DN in T2D patients. The regulation of this miRNA seems to be related to the recruitment of leukocytes to vascular walls induced by pro-inflammatory and adhesion molecules.

The purpose of the study was to determine the impact of weight loss through calorie restriction on metabolic profile, and inflammatory and oxidative stress parameters in metabolically healthy (MHO) and unhealthy (MUHO) obese individuals. A total of 74 subjects (34 MHO and 40 MUHO) received two cycles of a very low-calorie diet, alternating with a hypocaloric diet for 24 weeks. Biochemical, oxidative stress, and inflammatory markers, as well as serum metabolomic analysis by nuclear magnetic resonance, were performed at baseline and at the end of the intervention. After the diet, there was an improvement in insulin resistance, as well as a significant decrease in inflammatory parameters, enhancing oxidative damage, mitochondrial membrane potential, glutathione, and antioxidant capacity. This improvement was more significant in the MUHO group. The metabolomic analysis showed a healthier profile in lipoprotein profile. Lipid carbonyls also decrease at the same time as unsaturated fatty acids increase. We also display a small decrease in succinate, glycA, alanine, and BCAAs (valine and isoleucine), and a slight increase in taurine. These findings show that moderate weight reduction leads to an improvement in lipid profile and subfractions and a reduction in oxidative stress and inflammatory markers; these changes are more pronounced in the MUHO population.

Inflammation, oxidative stress, and mitochondrial function are implicated in the development of obesity and its comorbidities. The purpose of this study was to assess the impact of weight loss through calorie restriction on the metabolic profile, inflammatory and oxidative stress parameters, and mitochondrial respiration in an obese population. A total of 109 subjects underwent two cycles of a very low-calorie diet alternated with a low-calorie diet (24 weeks). We analyzed biochemical and inflammatory parameters in serum, as well as oxidative stress markers, mRNA antioxidant gene expression, and mitochondrial respiration in peripheral blood mononuclear cells (PBMCs). After the intervention, there was an improvement in both insulin resistance and lipid profiles, including cholesterol subfractions. Weight loss produced a significant reduction in mitochondrial ROSs content and an increase in glutathione levels, coupled with an enhancement in the mRNA expression of antioxidant systems (SOD1, GSR, and CAT). In addition, a significant improvement in basal oxygen consumption, maximal respiration, and ATP production was observed. These findings demonstrate that moderate weight loss can improve insulin resistance, lipid profiles and subfractions, inflammatory and oxidative stress parameters, and mitochondrial respiration. Therefore, we can affirm that dietary intervention can simultaneously achieve significant weight loss and improve metabolic profile and mitochondrial function in obesity.

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 evaluated. Results DRM + I patients showed lower albumin, prealbumin, transferrin, and retinol-binding protein levels with respect to the NN group ( p  < 0.05), differences that were less noticeable in the DRM-I group. DRM + I was associated with a significant increase in hsCRP and IL6 vs the NN and DRM-I groups, and TNFα was increased in both DRM vs NN. DRM was characterised by increased oxidative stress, which was marked by a significant increase in ROS levels and a decrease in mitochondrial membrane potential in the DRM + I group. An evident reduction in mitochondrial oxygen consumption and glutathione concentration was observed in both DRM groups, and was accompanied by increased leukocyte adhesion and adhesion molecules and decreased rolling velocity in the DRM + I group. Furthermore, percentage of weight loss was negatively correlated with albumin, prealbumin, transferrin, O 2 consumption, glutathione and leukocyte rolling velocity, and positively correlated with hsCRP, IL6, TNFα, ROS, leukocyte adhesion, and VCAM-1. Conclusions Our results show that DRM is associated with oxidative stress and an inflammatory state, with a deterioration of endothelial dysfunction in the DRM + I population.

Retinol binding protein 4 (RBP4) is an adipokine that may contribute to the development of insulin resistance. However, how this adipokine is affected and its possible involvement in lipid metabolism in obese patients with varying degrees of insulin resistance is yet to be determined. A total of 299 middle-aged morbid obese patients (BMI>40 kg/m(2)) were divided in euglycemic, metabolic syndrome or type 2 diabetic. Anthropometric measurements, biochemical variables and systemic RBP4 levels were determined. RBP4 levels were significantly higher in patients with metabolic syndrome and type 2 diabetes than in euglycemic subjects (42.9±14.6; 42.3±17.0 and 37.4±11.7 µg/ml, respectively) and correlated with triglycerides but not with those of HOMA-IR in the whole population. The multivariate regression model revealed that triglycerides were the strongest predictor of systemic RBP4 levels. Analysis of lipoprotein subfractions in a subpopulation of 80 subjects showed an altered profile of insulin resistant states characterized by higher VLDL, sdLDL and small HDL percentages and lower large HDL percentage. Although RBP4 levels correlated significantly with LDL particle size and small HDL percentage, the latter parameter was independently associated only with RBP4. Our study reveals that systemic RBP4 levels could play an important role in lipid metabolism in morbid obesity, increasing triglyceride levels and contributing to the formation of small HDL.