Metabolic Syndrome, Cognitive Impairment and the Role of Diet: A Narrative Review

Background: This narrative review presents the association between metabolic syndrome (MetS), along with its components, and cognition-related disorders, as well as the potential reversal role of diet against cognitive impairment by modulating MetS. Methods: An electronic research in Medline (Pubmed) and Scopus was conducted. Results: MetS and cognitive decline share common cardiometabolic pathways as MetS components can trigger cognitive impairment. On the other side, the risk factors for both MetS and cognitive impairment can be reduced by optimizing the nutritional intake. Clinical manifestations such as dyslipidemia, hypertension, diabetes and increased central body adiposity are nutrition-related risk factors present during the prodromal period before cognitive impairment. The Mediterranean dietary pattern stands among the most discussed predominantly plant-based diets in relation to cardiometabolic disorders that may prevent dementia, Alzheimer’s disease and other cognition-related disorders. In addition, accumulating evidence suggests that the consumption of specific dietary food groups as a part of the overall diet can improve cognitive outcomes, maybe due to their involvement in cardiometabolic paths. Conclusions: Early MetS detection may be helpful to prevent or delay cognitive decline. Moreover, this review highlights the importance of healthy nutritional habits to reverse such conditions and the urgency of early lifestyle interventions.

Skeletal Muscle Microvascular Dysfunction in Obesity-Related Insulin Resistance: Pathophysiological Mechanisms and Therapeutic Perspectives

Obesity is a worrisomely escalating public health problem globally and one of the leading causes of morbidity and mortality from noncommunicable disease. The epidemiological link between obesity and a broad spectrum of cardiometabolic disorders has been well documented; however, the underlying pathophysiological mechanisms are only partially understood, and effective treatment options remain scarce. Given its critical role in glucose metabolism, skeletal muscle has increasingly become a focus of attention in understanding the mechanisms of impaired insulin function in obesity and the associated metabolic sequalae. We examined the current evidence on the relationship between microvascular dysfunction and insulin resistance in obesity. A growing body of evidence suggest an intimate and reciprocal relationship between skeletal muscle microvascular and glucometabolic physiology. The obesity phenotype is characterized by structural and functional changes in the skeletal muscle microcirculation which contribute to insulin dysfunction and disturbed glucose homeostasis. Several interconnected etiologic molecular mechanisms have been suggested, including endothelial dysfunction by several factors, extracellular matrix remodelling, and induction of oxidative stress and the immunoinflammatory phenotype. We further correlated currently available pharmacological agents that have deductive therapeutic relevance to the explored pathophysiological mechanisms, highlighting a potential clinical perspective in obesity treatment.

Natural AMPK Activators in Cardiovascular Disease Prevention

Cardiovascular diseases (CVD), as a life-threatening global disease, is receiving worldwide attention. Seeking novel therapeutic strategies and agents is of utmost importance to curb CVD. AMP-activated protein kinase (AMPK) activators derived from natural products are promising agents for cardiovascular drug development owning to regulatory effects on physiological processes and diverse cardiometabolic disorders. In the past decade, different therapeutic agents from natural products and herbal medicines have been explored as good templates of AMPK activators. Hereby, we overviewed the role of AMPK signaling in the cardiovascular system, as well as evidence implicating AMPK activators as potential therapeutic tools. In the present review, efforts have been made to compile and update relevant information from both preclinical and clinical studies, which investigated the role of natural products as AMPK activators in cardiovascular therapeutics.

Bronchial asthma in the genetic framework of cardiovascular continuum syntropy

Hypertension, coronary heart disease, myocardial infarction, obesity, and type 2 diabetes mellitus are common comorbidities in patients with bronchial asthma. The causes for developing these diseases are multifactorial and involve inherited genetic factors. However, little is known about the genes contributing to the development of comorbidities in bronchial asthma and cardiovascular disease continuum.Objective. To examine the associations of genetic polymorphic variants potentially involved in the development of bronchial asthma comorbid with hypertension, coronary heart disease, type 2 diabetes mellitus, and obesity.Material and Methods. Genotyping of 92 single nucleotide polymorphisms (SNPs) was performed using MALDI-TOF mass spectrometry in patients with bronchial asthma associated with cardiovascular/metabolic disorders (n = 162) compared with a control group of apparently healthy individuals (n = 153).Results. The development of bronchial asthma phenotypes comorbid with cardiovascular/metabolic disorders was associated with the particular genetic variants affecting the expression of genes including CAT, TLR4, ELF5, ABTB2, UTP25, TRAF3IP3, NFKB1, LOC105377347, C1orf74, IRF6, and others in the target organs of study disease profile. Only one SNP (rs11590807), which is regulatory for the UTP25, IRF6, TRAF3IP3, and RP1-28O10.1 genes, was associated with all studied comorbid phenotypes of bronchial asthma and diseases of cardiovascular continuum.Conclusion. The obtained results demonstrated that the identified SNPs affecting the expression of many genes may serve as potential biological markers of complex causal relationships between bronchial asthma and cardiometabolic disorders.

Comorbidity of NAFLD and GERD as a cardiometabolic phenomenon

The aim of the study was to study the cardiometabolic characteristics in individuals with an associated course of non-alcoholic fatty liver disease (NAFLD) and gastroesophageal reflux disease (GERD) in comparison with isolated cases of diseases.Materials and methods. The study included 120 patients (30 — with GERD, 30 — with NAFLD, 30 — with GERD + NAFLD. Work design — prospective parallel comparative study with 2 stages. Stage I — inclusion in the study, assessment of the main cardiometabolic, cardio vascular rice (CVR) according to the SCORE scale and the Framingham scale. Stage II — follow-up of the participants for 5 years, re-examination and riskmetry.Results. It has been shown that with a combination of NAFLD and GERD, the pathogenetic mechanisms involved in the formation of NAFLD (especially in steatohepatitis) affect the key characteristics of the metabolic profile and the state of the CV system to a greater extent than GERD. The total CVR values in this category of patients were: 4.8 — SCORE; 13.4 — on the Framingham scale. Over 5 years in this group, 10 (33% of the initial) newly diagnosed cases of CVD were verified: 6 — AH, 3 — IHD, 1 — AH + IHD. CVR for the NAFLD and GERD group increased: according to the SCORE scale — from low risk (4.8) to high (8.9), and according to the Framingham scale, the dynamics was even more negative (from 13.4 to 18.6).Conclusion. Kinds of cardiometabolic disorders in persons with comorbidity of NAFLD and GERD have been proven, which can form the prerequisites for structural cardiovascular changes, including the risks of CVD. This can be a rationale for carrying out additional preventive measures for the groups of patients under discussion, especially in the case of their associated course, as measures for the early preclinical diagnosis of CVR factors and for timely correction of the identified disorders.

Plasma Acylcarnitines during Pregnancy and Neonatal Anthropometry: A Longitudinal Study in a Multiracial Cohort

As surrogate readouts reflecting mitochondrial dysfunction, elevated levels of plasma acylcarnitines have been associated with cardiometabolic disorders, such as obesity, gestational diabetes, and type 2 diabetes. This study aimed to examine prospective associations of acylcarnitine profiles across gestation with neonatal anthropometry, including birthweight, birthweight z score, body length, sum of skinfolds, and sum of body circumferences. We quantified 28 acylcarnitines using electrospray ionization tandem mass spectrometry in plasma collected at gestational weeks 10–14, 15–26, 23–31, and 33–39 among 321 pregnant women from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons. A latent-class trajectory approach was applied to identify trajectories of acylcarnitines across gestation. We examined the associations of individual acylcarnitines and distinct trajectory groups with neonatal anthropometry using weighted generalized linear models adjusting for maternal age, race/ethnicity, education, parity, gestational age at blood collection, and pre-pregnancy body mass index (BMI). We identified three distinct trajectory groups in C2, C3, and C4 and two trajectory groups in C5, C10, C5–DC, C8:1, C10:1, and C12, respectively. Women with nonlinear decreasing C12 levels across gestation (5.7%) had offspring with significantly lower birthweight (−475 g; 95% CI, −942, −6.79), birthweight z score (−0.39, −0.71, −0.06), and birth length (−1.38 cm, −2.49, −0.27) than those with persistently stable C12 levels (94.3%) (all nominal p value < 0.05). Women with consistently higher levels of C10 (6.1%) had offspring with thicker sum of skinfolds (4.91 mm, 0.85, 8.98) than did women with lower levels (93.9%) during pregnancy, whereas women with lower C10:1 levels (12.6%) had offspring with thicker sum of skinfolds (3.23 mm, 0.19, 6.27) than did women with abruptly increasing levels (87.4%) (p < 0.05). In conclusion, this study suggests that distinctive trajectories of C10, C10:1, and C12 acylcarnitine levels throughout pregnancy were significantly associated with neonatal anthropometry.

Assessment of Intramuscular Fat and Correlation with Body Composition in Patients with Rheumatoid Arthritis and Spondyloarthritis: A Pilot Study

Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are associated with changes in body composition. Ectopic intramuscular fat (IMAT) may alter muscle function and contribute to cardiometabolic disorders. In a pilot study, we analyzed IMAT in the calf with peripheral quantitative computed tomography (pQCT) and examined correlations between IMAT quantity and body composition parameters. In 20 patients with active RA and 23 with active SpA, IMAT was correlated with visceral fat (VAT; r = 0.5143 and 0.6314, respectively; p < 0.05) and total lean mass (r = 0.5414 and 0.8132, respectively; p < 0.05), but not with whole body fat mass. Total lean mass mediated 16% and 33% of the effects of VAT on IMAT in RA and SpA, respectively. In both RA and SpA, calf muscle area was correlated with total lean mass (r = 0.5940 and r = 0.8597, respectively; p < 0.05) and fat area was correlated with total body fat (r = 0.6767 and 0.5089, respectively; p < 0.05) and subcutaneous fat (r = 0.6526 and 0.5524, respectively; p < 0.05). Fat area was inversely correlated with handgrip and walking tests, and it was associated with disease activity and disability. We showed that ectopic IMAT, measured with pQCT, was correlated with VAT, but not with total body fat, in RA and SpA. This result suggests that metabolically active fat was specifically associated with IMAT.

The Role of Anti-Inflammatory Adipokines in Cardiometabolic Disorders: Moving beyond Adiponectin

The global burden of obesity has multiplied owing to its rapidly growing prevalence and obesity-related morbidity and mortality. In addition to the classic role of depositing extra energy, adipose tissue actively interferes with the metabolic balance by means of secreting bioactive compounds called adipokines. While most adipokines give rise to inflammatory conditions, the others with anti-inflammatory properties have been the novel focus of attention for the amelioration of cardiometabolic complications. This review compiles the current evidence on the roles of anti-inflammatory adipokines, namely, adiponectin, vaspin, the C1q/TNF-related protein (CTRP) family, secreted frizzled-related protein 5 (SFRP5), and omentin-1 on cardiometabolic health. Further investigations on the mechanism of action and prospective human trials may pave the way to their clinical application as innovative biomarkers and therapeutic targets for cardiovascular and metabolic disorders.