At present, obesity, as a part of metabolic syndrome, represents the leading factor for disability, and is correlated with higher inflammation status, morbidity, and mortality. The purpose of our study is to add new insights to the present body of knowledge regarding the correlations between chronic systemic inflammation and severe obesity, which cannot be treated without considering other metabolic syndrome conditions. Biomarkers of high-level chronic inflammation are recognized as important predictors of pro-inflammatory disease. Besides the well-known pro-inflammatory cytokines, such as WBCs (white blood cells), IL-1 (interleukin-1), IL-6 (interleukin-6), TNF-alpha (tumor necrosis factor-alpha), and hsCRP (high-sensitivity C-reactive protein), as well as anti-inflammatory markers, such as adiponectin and systemic inflammation, can be determined by a variety of blood tests as a largely available and inexpensive inflammatory biomarker tool. A few parameters, such as the neutrophil-to-lymphocyte ratio; the level of cholesterol 25-hydroxylase, which is part of the macrophage-enriched metabolic network in adipose tissue; or levels of glutamine, an immune–metabolic regulator in white adipose tissue, are markers that link obesity to inflammation. Through this narrative review, we try to emphasize the influence of the weight-loss process in reducing obesity-related pro-inflammatory status and associated comorbidities. All data from the presented studies report positive results following weight-loss procedures while improving overall health, an effect that lasts over time, as far as the existing research data show.

/pdf/a-comprehensive-summary-of-the-current-understanding-of-the-2fqt255w.pdf

A Comprehensive Summary of the Current Understanding of the Relationship between Severe Obesity, Metabolic Syndrome, and Inflammatory Status

Obesity is characterized by increased oxidative stress, which, in a vicious circle, promotes chronic low-grade inflammation. Melatonin, a well-documented antioxidant, might be useful as a supplement to enhance the cardiometabolic benefits of any body weight reduction program (BWRP). 

Effects of Melatonin on Exercise-Induced Oxidative Stress in Adults with Obesity Undergoing a Multidisciplinary Body Weight Reduction Program

The aim of this study was to evaluate the potential interplay between a carbohydrate diet and inflammation in atherosclerotic cardiovascular disease (ASCVD) development. ATTICA is a prospective observational study of 3042 adults free of cardiovascular disease (CVD) who were recruited in 2002 and followed for 20 years. Baseline data on carbohydrate intake and inflammatory biomarker levels were collected. Participants were stratified by carbohydrate intake (low vs. high: &lt;/&gt; 190 g/day) and carbohydrate quality. At the 20-year follow-up in 2022, 1988 participants had complete data for CVD assessment. The overall quantity and quality of carbohydrate intake did not show a significant association with CVD incidence; inflammatory markers were positively correlated with an increased risk of CVD (p-values &lt; 0.05). Chronic systemic inflammation seems to affect the CVD risk of participants who had a higher carbohydrate intake more substantially, as compared to those with low intake. Additionally, individuals with higher high carbohydrate/low fiber intake experienced a higher risk of inflammation-related CVD, compared to those with high carbohydrate/high fiber intake. The presented findings revealed that the effect of inflammation markers on the CVD risk is influenced both by the amount and quality of carbohydrate intake, irrespective of overall dietary habits and clinical and lifestyle characteristics. 

The Impact of Dietary Carbohydrates on Inflammation-Related Cardiovascular Disease Risk: The ATTICA Study (2002–2022)

Metabolic syndrome (MetS) is accompanied by chronic low-grade inflammation, and inflammatory markers like high-sensitivity C-reactive protein(hs-CRP), interleukin-6(IL-6), and homocysteine(Hcy) contribute to inflammation, obesity, and insulin resistance. Adiponectin(AdipoQ) and interleukin-10(IL-10) are anti-inflammatory markers that play protective roles in MetS. This study aimed to investigate the association between these biochemical marker changes and MetS in a sample of the Tehranian population during six years of follow-up.In this longitudinal study, 340 adults at baseline and after a six-year follow-up, aged ≥18 years, were selected randomly from the Tehran Lipid and Glucose Study (TLGS). MetS was defined according to the Joint Interim Statement (JIS) criteria. Individuals were categorized into four groups based on their MetS status at baseline and follow-up: 1) non-MetS: participants who did not have MetS at both baseline and follow-up; 2) incident MetS: participants who did not have MetS at baseline but developed MetS during the follow-up ; 3) recovery MetS: participants who had MetS at baseline but no longer had MetS during the follow-up; 4) persistent MetS: participants who had MetS both at baseline and follow-up.The mean follow-up time was 6.1 years. There were 176 subjects in the non-MetS group, 35 in the incident MetS group, 41 in the recovery MetS group, and 88 in the persistent MetS group. Increases in the levels of both hs-CRP 1.40 (95% CI: 1.15, 1.71, p = 0.001) and IL-6 1.09 (95% CI: 1.03, 1.17, p = 0.004) significantly increased the odds of the incident and persistent MetS, respectively. The area under the ROC curve (AUC) was more than 0.69 (p < 0.000) for hs-CRP in predicting MetS incidence and more than 0.86 (p < 0.000) for IL-6 in predicting MetS persistence.After a six-year average follow-up, hs-CRP and IL-6 levels were deemed more reliable predictors of MetS incidence and persistence, respectively. 

pdf/association-between-baseline-and-changes-in-adiponectin-4dti0sazoh.pdf

Association between baseline and changes in adiponectin, homocysteine, high-sensitivity C-reactive protein, interleukin-6, and interleukin-10 levels and metabolic syndrome incidence: Tehran lipid and glucose study

Owing to the great demand for healthy ageing promotion, and the anti-ageing reputation of anthocyanins and amino acids, we aimed to assess the effect of anthocyanin- and anti-ageing amino acids-enriched pigmented rice innovation on age-related cognitive decline, facial wrinkles, and a cardiovascular risk, and explored its mechanisms and safety. A total of 90 male and female volunteers (45–65 years old) participated in a 3-arm randomized, double blinded, placebo-controlled parallel study for 12 weeks. They were randomly allocated to one of the following groups: placebo, “Zuper rice” (Zup) 2 g/day and “Zuper Rice” 4 g/day. Cognition, facial wrinkles, atherogenic index in plasma (AIP), telomere length, telomerase, oxidative stress and inflammatory markers, together with safety parameters, were assessed every 6 weeks until the end of the study and compared to the baseline data. A high dose of “Zup” improved cognition, facial wrinkles, AIP and oxidative stress, while a low dose of “Zup” improved cognition, telomere length, telomerase and inflammation. No toxicity signs were observed. Therefore, “Zup” is a potential healthy ageing promotion innovation which improves telomere length, telomerase activity and inflammation at a low dose, resulting in an improvement in cognitive decline and the suppression of oxidative stress. At a high dose, it gives rise to improvements in cognition, facial wrinkles and cardiovascular risk. 

An Anthocyanin- and Anti-Ageing Amino Acids-Enriched Pigmented Rice Innovation Promotes Healthy Ageing Through the Modulation of Telomere, Oxidative Stress and Inflammation Reduction: A Randomized Clinical Trial

Background Dietary interventions may modulate inflammatory indicators, but the correlations between dietary intervention and inflammatory markers in metabolic syndrome (MetS) settings remain opaque. Objective To evaluate the effects of dietary intervention on interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) in patients with MetS by systematic review and meta-analysis. Methods Databases, including PubMed, Embase, Cochrane Library, Scopus, and Google scholar, were searched from June 2011 to June 2021 for relevant available articles. Standardized mean difference (SMD) was generated as effect size by meta-analysis for continuous variants, including IL-1β, IL-6, TNF-α, and CRP levels. Then, according to study characteristics by dietary patterns of the intervention, subgroup analyses were performed. Results Finally, 13 studies comprising a total of 1,101 participants were included for the meta-analysis. IL-6 levels in dietary patients were significantly lower than controls (SMD = −0.30, 95% CI = −0.55, 0.04, p = 0.02, I2 = 64%). However, IL-1β, TNF-α, and CRP levels did not change significantly compared with the control group. Sensitivity analyses further yielded similar results. Conclusions Dietary intervention may help decrease IL-6 rather than IL-1β, TNF-α, or CRP levels in patients with MetS.

/pdf/effects-of-dietary-intervention-on-inflammatory-markers-in-25mlursq.pdf

Effects of Dietary Intervention on Inflammatory Markers in Metabolic Syndrome: A Systematic Review and Meta-Analysis

Background: Lipid pathways have been implicated in the pathogenesis of osteoporosis (OP). Lipid-lowering drugs may be used to prevent and treat OP. However, the causal interpretation of results from traditional observational designs is controversial by confounding. We aimed to investigate the causal association between genetically proxied lipid-lowering drugs and OP risk.Methods: We conducted two-step Mendelian randomization (MR) analyses to investigate the causal association of genetically proxied lipid-lowering drugs on the risk of OP. The first step MR was used to estimate the associations of drug target genes expression with low-density lipoprotein cholesterol (LDL-C) levels. The significant SNPs in the first step MR were used as instrumental variables in the second step MR to estimate the associations of LDL-C levels with forearm bone mineral density (FA-BMD), femoral neck BMD (FN-BMD), lumbar spine BMD (LS-BMD) and fracture. The significant lipid-lowering drugs after MR analyses were further evaluated for their effects on bone mineralization using a dexamethasone-induced OP zebrafish model.Results: The first step MR analysis found that the higher expression of four genes (HMGCR, NPC1L1, PCSK9 and PPARG) was significantly associated with a lower LDL-C level. The genetically decreased LDL-C level mediated by the PPARG was significantly associated with increased FN-BMD (BETA = −1.38, p = 0.001) and LS-BMD (BETA = −2.07, p = 3.35 × 10−5) and was marginally significantly associated with FA-BMD (BETA = −2.36, p = 0.008) and reduced fracture risk (OR = 3.47, p = 0.008). Bezafibrate (BZF) and Fenofibric acid (FBA) act as PPARG agonists. Therefore genetically proxied BZF and FBA had significant protective effects on OP. The dexamethasone-induced OP zebrafish treated with BZF and FBA showed increased bone mineralization area and integrated optical density (IOD) with alizarin red staining.Conclusion: The present study provided evidence that BZF and FBA can increase BMD, suggesting their potential effects in preventing and treating OP. These findings potentially pave the way for future studies that may allow personalized selection of lipid-lowering drugs for those at risk of OP.

A Mendelian randomization study for drug repurposing reveals bezafibrate and fenofibric acid as potential osteoporosis treatments

Background and objective Around 33.5 million patients suffered from atrial fibrillation (AF), causing complications and increasing mortality and disability rate. Upstream treatment for AF is getting more popular in clinical practice in recent years. The angiotensin receptor-neprilysin inhibitor (ARNI) is one of the potential treatment options. Our study aimed to investigate the effect of ARNI on atrial electrical instability and structural remodeling in AF. Methods Our research consisted of two parts – a retrospective real-world clinical study and an animal experiment on calmness to verify the retrospective founding. In the retrospective study, we reviewed all patients (n = 110) who had undergone the first AF ablation from 1 August 2018 to 1 March 2022. Patients with ARNI (n = 36) or angiotensin II receptor antagonist (ARB) (n = 35) treatment were enrolled. Their clinical data, ultrasound cardiogram (UCG) and Holter parameters were collected before radiofrequency catheter ablation (RFCA) as baseline and at 24-week follow-up. Univariate and multivariate logistic regression analysis were performed. In the animal experiment, we established an AF model (n = 18) on canines by rapid atrial pacing. After the successful procedure of pacing, all the 15 alive beagles were equally and randomly assigned to three groups (n = 5 each): Control group, ARB group, and ARNI group. UCG was performed before the pacing as baseline. Physiological biopsy, UCG, and electrophysiological study (EPS) were performed at 8-week. Results Clinical data showed that the atrial arrhythmia rate at 24-week was significantly lower in ARNI group compared to ARB group (P < 0.01), and ARNI was independently associated with a lower atrial arrhythmia rate (P < 0.05) at 24-week in multivariate regression logistic analysis. In the animal experiment, ARNI group had a higher atrial electrical stability score and a shorter AF duration in the EPS compared to Control and ARB group (P < 0.05). In the left atrium voltage mapping, ARNI group showed less low voltage and disordered zone compared to Control and ARB group. Compared to Control group, right atrium diameter (RAD), left ventricle end-diastolic volume index (LVEDVI), E/A, and E/E′ were lower in ARNI group (P < 0.05) at the 8-weeks follow-up, while left atrium ejection fraction (LAEF) and left ventricle ejection fraction (LVEF) were higher (P < 0.01). Compared to ARB group, LVEF was higher in ARNI group at the 8-week follow-up (P < 0.05). ARB and ARNI group had a lower ratio of fibrotic lesions in the left atrium tissues compared to Control group (P < 0.01), but no difference was found between the ARB and the ARNI group. Conclusion ARNI could reduce atrial electrical instability in AF in comparison with ARB in both retrospective study and animal experiment.

/pdf/effect-of-angiotensin-receptor-neprilysin-inhibitor-on-181wmr0y.pdf

Effect of angiotensin receptor-neprilysin inhibitor on atrial electrical instability in atrial fibrillation

WITHDRAWN: Higher intakes of dietary caffeine are associated with 25-hydroxyvitamin D deficiency: a study from the NHANES

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Effects of Dietary Intervention on Inflammatory Markers in Metabolic Syndrome: A Systematic Review and Meta-Analysis

A Mendelian randomization study for drug repurposing reveals bezafibrate and fenofibric acid as potential osteoporosis treatments

Effect of angiotensin receptor-neprilysin inhibitor on atrial electrical instability in atrial fibrillation

WITHDRAWN: Higher intakes of dietary caffeine are associated with 25-hydroxyvitamin D deficiency: a study from the NHANES