Pathogenesis Of Metabolic Syndrome Research Articles

Association of serum immunoglobulin M and immunoglobulin G antibody levels with different indicators of metabolic syndrome

Background: Metabolic syndrome (MS) is an assemblage of biochemical derangements of glucose metabolism, dyslipidemia, hypertension, and central obesity allied with implacable low-grade inflammation. Aims and Objectives: The current cross-sectional study was conducted to evaluate the levels of serum Immunoglobulin IgM, and IgG concentrations in subjects with and without MS. Materials and Methods: The study population included 50 adults with MS as cases confirmed by estimation of serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), Fasting Plasma Glucose, waist circumference, and blood pressure. Serum IgM and IgG levels were evaluated in cases and controls (from a healthy population), followed by statistical analysis, with the significance level set at P<0.05. Results: The comparison of the serum IgM levels between the case and control groups revealed that the level was significantly higher in the former (P<0.001) compared to the latter, but no statistically significant difference existed in the IgG values. Correlation analysis showed significant positive correlation of IgM with TG (ρ=+0.870, P<0.001), waist circumference (ρ=+0.683, P=0.009) and negative correlation with HDL-C (ρ=−0.751, P<0.001). A significant positive correlation of IgG with waist circumference (ρ=+0.889, P<0.001) was derived. Regression analysis affirmed that statistically, TG (R2=0.768), waist circumference (R2=0.751), and HDL-C (R2=0.705) significantly explained the variance in IgM, whereas IgG was related to only waist circumference. Conclusion: The present study provides a novel perspective that IgM may be involved in the pathogenesis of MS in a population from eastern India, and the outcome suggests the association between IgM and MS may be through lipid metabolism disorders and obesity.

The role of the neural NO synthase adapter protein in the pathogenesis of metabolic syndrome and type 2 diabetes mellitus

The pathogenesis of metabolic syndrome (MS) is characterized by obesity, hypertension, dyslipidemia and insulin resistance. MS increases the risk of developing type 2 diabetes mellitus (DM2). The neuronal isoform of nitric oxide synthase (nNOS) is defined by complex protein-protein interactions, since nNOS, unlike other isoforms of NOS,contains a C-terminal PDZ domain, which allows it to conjugate with other proteins and, first of all, to interact with an adapter of neuronal, or type 1, nitric oxide synthase (NOS1AP), also denoted CAPON in our work. Changes in the interaction between nNOS and NOS1AP lead to metabolic disorders in brain, heart, liver and skeletal muscles, which plays a key role in the development of MS and T2DM. NOS1AP, interacting with the PDZ domain of nNOS, competes with the postsynaptic density protein (PSD95) and regulates the stability of subcellular localization of nNOS and enzyme expression during synapse formation. NOS1AP promotes nNOS binding to targets such as small GTPase (Dexras1), synapsines, regulating the formation of dendritic roots, mediates activation of the nNOS-p38MAP kinase pathway during excitotoxicity. It has been shown that single-nucleotide polymorphism of the NOS1AP gene and its overexpression in the myocardium leads to the manifestation of long QT syndrome, which is most clearly manifested in elderly patients with DM2. It was found that the genetic polymorphism of NOS1AP affects insulin secretion when using calcium blockers, and can promote the development of DM2. The functional role of NOS1AP in stabilizing the functions of skeletal muscle nNOS in the cytoskeletal complex associated with dystrophin/utrophin was discovered. The purpose of the review is to provide updated information on the role of NOS1AP and the nNOS/NOS1AP complex in the pathogenesis of MS and DM2. The potential molecular mechanisms of the interaction of NOS1AP with nNOS and with other proteins, which leads to change in nNOS activity, localization and content, are discussed.

The Role of the Gut Microbiome and the Hepatic Axis in the Pathogenesis of Metabolic Syndrome and Therapeutics

The increased global prevalence of viral and noninfectious liver illnesses has coincided with a surge in scientific interest in gut microbiota (GM), a multispecies community of bacteria, fungi, archaea, and protozoans. Dietary nutrients that make up the host’s microbiome are responsible for maintaining intestinal homeostasis, whereas a disconnect between gut flora and nutrition might have serious consequences for digestive health. The risk of liver dysfunction was continuously elevated by changes in the commensal bacteria of the gut microbiome, which were carried to the liver via the portal vein. Insights into the role of gut microbiota in alcoholic liver disease, nonalcoholic liver disease, primary sclerosing cholangitis, and other liver disorders, as well as their link to liver cancer, continue to emerge. Systemic host defence against infections by the gut microbiota depends on the interplay between the microbiome, liver immunology, and liver disorders. Translocation of microbiota to the liver following injury and/or inflammation may mediate dysbiosis and the formation of gut microbial metabolite. This review discusses the role of the gut microbiota in connection to dysbiosis and how this knowledge might help us better understand the pathophysiology of various liver illnesses.

Sarcoidosis as a disease associated with metabolic syndrome

The review summarizes and analyzes the results of domestic and major foreign studies of recent years concerning the prevalence of metabolic syndrome components and the explanation of their role in the mechanisms of sarcoidosis development. A deep understanding of the pathogenesis of metabolic syndrome (MS) in terms of the role in it of risk factors for a severe course and complications of most socially sensitive noncommunicable diseases clustered within MS can underly the development of effective pathogen-specific approaches to MS treatment.

Inflammatory biomarkers link perceived stress with metabolic dysregulation

ObjectivePerceived stress has been identified as a risk factor for metabolic syndrome. However, the intermediate pathways underlying this relationship are not well understood. Inflammatory responses may be one process by which stress leads to metabolic dysregulation. Prior work has shown that chronic stress is associated with elevated systemic inflammation and that altered inflammatory activity contributes to the pathogenesis of metabolic syndrome. The current analyses tested this hypothesis by examining inflammation as a pathway by which perceived stress affects metabolic health. MethodsData from the Midlife in the United States Study (MIDUS) (N = 648; Mean age = 52.3) provided measures of perceived stress, inflammatory biomarkers [C-reactive protein (CRP), interleukin-6 (IL-6), E-selectin, fibrinogen, intracellular adhesion molecule-1 (ICAM-1)] and metabolic health markers. Confirmatory factor analysis (CFA) was used to confirm the fit of a hierarchical model of metabolic syndrome in our sample. Structural equation modeling (SEM) was used to test the assumption that inflammation mediates the association between perceived stress and the latent factor representing metabolic syndrome. ResultsThe CFA of metabolic syndrome demonstrated excellent goodness of fit to our sample [CFI = 0.97, TLI = 0.95, RMSEA = 0.06, SMSR = 0.05]. Mediation analysis with SEM revealed that the indirect pathway linking stress to metabolic dysregulation through inflammation was significant [B = 0.08, SE = 0.01, z = 3.69, p < .001, 95% confidence interval CI (0.04, 0.13)]. ConclusionsThese results suggest that inflammatory biomarkers are a viable explanatory pathway for the relationship between perceived stress and metabolic health consequences. Interventions that target psychosocial stress may serve as cost-effective and accessible treatment options for mitigating inflammatory health risks.

Circulating MicroRNA-30a, Beclin1 and Their Association with Different Variables in Females with Metabolically Healthy /Unhealthy Obesity.

Obesity is associated with metabolic and cardiovascular co-morbidities. It is important to determine the factors associated with metabolic derangement in obesity. Autophagy plays a major role in the pathogenesis of metabolic syndrome. MicroRNA-30a targets beclin1, the main regulator of autophagy. We assess circulating microRNA-30a and serum beclin1 in women with metabolically unhealthy obesity (MUO), women with metabolically healthy obesity (MHO) and non-obese healthy control and determine their relationship with different clinical and metabolic variables in women with obesity. This cross-sectional study included 34 women with MHO, 34 with MUO, and 20 healthy non-obese women. Blood pressure, body mass index (BMI), and waist circumference were recorded. Glycemic and lipid indices, urinary albumin-to-creatinine ratio, ALT, AST, microRNA-30a expression in serum were measured using real-time polymerase chain reaction and beclin1 by enzyme-linked immunosorbent assay were measured. The expression of microRNA-30a was significantly higher, and beclin1 level was significantly lower in women with MUO compared to those in women with MHO (P<0.001; for both). People with MUO were significantly older (P<0.001) and had higher TSH (P=0.006), HbA1c (P<0.001), triglyceride (P<0.001), and ALT (P<0.001) compared to women with MHO. However, there was no significant difference between the two groups in any anthropometric measurements, HDL-C or LDL-C. In univariate analyses, age, ALT, TSH, microRNA-30a, and beclin1 were significantly correlated with the MUO phenotype (P<0.001; for all). Significance was confirmed in the multivariate analysis for microRNA-30a (95% CI 1.317-28.252; P=0.021). MicroRNA-30a, beclin1, age, and ALT and TSH levels were significantly associated with the MUO phenotype, among which microRNA-30a was the best indicator of metabolic syndrome in women with obesity.

Thermogenic Modulation of Adipose Depots: A Perspective on Possible Therapeutic Intervention with Early Cardiorenal Complications of Metabolic Impairment.

Cardiovascular complications of diabetes and obesity remain a major cause for morbidity and mortality worldwide. Despite significant advances in the pharmacotherapy of metabolic disease, the available approaches do not prevent or slow the progression of complications. Moreover, a majority of patients present with significant vascular involvement at early stages of dysfunction prior to overt metabolic changes. The lack of disease-modifying therapies affects millions of patients globally, causing a massive economic burden due to these complications. Significantly, adipose tissue inflammation was implicated in the pathogenesis of metabolic syndrome, diabetes, and obesity. Specifically, perivascular adipose tissue (PVAT) and perirenal adipose tissue (PRAT) depots influence cardiovascular and renal structure and function. Accumulating evidence implicates localized PVAT/PRAT inflammation as the earliest response to metabolic impairment leading to cardiorenal dysfunction. Increased mitochondrial uncoupling protein 1 (UCP1) expression and function lead to PVAT/PRAT hypoxia and inflammation as well as vascular, cardiac, and renal dysfunction. As UCP1 function remains an undruggable target so far, modulation of the augmented UCP1-mediated PVAT/PRAT thermogenesis constitutes a lucrative target for drug development to mitigate early cardiorenal involvement. This can be achieved either by subtle targeted reduction in UCP-1 expression using innovative proteolysis activating chimeric molecules (PROTACs) or by supplementation with cyclocreatine phosphate, which augments the mitochondrial futile creatine cycling and thus decreases UCP1 activity, enhances the efficiency of oxygen use, and reduces hypoxia. Once developed, these molecules will be first-in-class therapeutic tools to directly interfere with and reverse the earliest pathology underlying cardiac, vascular, and renal dysfunction accompanying the early metabolic deterioration. SIGNIFICANCE STATEMENT: Adipose tissue dysfunction plays a major role in the pathogenesis of metabolic diseases and their complications. Although mitochondrial alterations are common in metabolic impairment, it was only recently shown that the early stages of metabolic challenge involve inflammatory changes in select adipose depots associated with increased uncoupling protein 1 thermogenesis and hypoxia. Manipulating this mode of thermogenesis can help mitigate the early inflammation and the consequent cardiorenal complications.

An analysis of the associations of high-sensitivity C-reactive protein and uric acid with metabolic syndrome components in Korean adults by sex: a cross-sectional study using the Korea national health and nutrition examination survey 2016–2018

BackgroundLow-grade inflammation plays a role in the pathogenesis of metabolic syndrome (MetS), and measuring levels of inflammatory molecules, such as high-sensitivity C-reactive protein (hs-CRP), may indicate Mets progression. Serum uric acid (SUA) has also been identified as an independent risk factor for MetS. This study aimed to investigate the association between MetS components and levels of serum hs-CRP and SUA using representative and reliable data for the Korean population.MethodsThis study used the data of the Korea National Health and Nutrition Examination Survey 2016–2018, a cross-sectional and nationally representative survey performed by the Korean Centers for Disease Control and Prevention.ResultsWe analysed the data of 13,454 individuals. High hs-CRP levels were observed in 1,164 (8.7%) subjects while 3,296 (24.5%) subjects had high SUA levels. Moreover, hs-CRP was negatively correlated with serum high-density lipoprotein (HDL) (OR, 1.703; 95% CI, 1.431–2.027). When stratified by sex, this trend remained, but the correlation was stronger in women than in men. Furthermore, high SUA levels were significantly associated with hypertension (HTN) (OR, 1.399; 95% CI, 1.210–1.616), hypertriglyceridemia (OR, 1.735; 95% CI, 1.486–2.026), and low HDL (OR, 1.257; 95% CI, 1.106–1.429), but not with diabetes mellitus (DM) (OR, 0.478; 95% CI, 0.382–0.597). When grouped by sex, this trend remained, however, all MetS components were found to be more prevalent in women with high SUA.ConclusionsOur findings showed that low HDL was more prevalent in subjects with high hs-CRP, and high SUA levels were observed in subjects with HTN, hypertriglyceridemia, and low HDL. However, the prevalence of high SUA was lower in diabetic subjects.

A simple dietary intervention to reduce inflammation and oxidative stress in individuals with metabolic syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Approximately 25% of the world's population have metabolic syndrome and those diagnosed have a two-fold risk of developing cardiovascular disease. Inflammation and oxidative stress are responsible for the pathogenesis of metabolic syndrome. Diets with a high intake of vegetables containing carotenoids, a type of antioxidants, are associated with reduced levels of inflammation and oxidative stress, yet interventions to increase vegetable intake have been difficult to adapt. We conducted a randomized controlled trial of a simple dietary antioxidant intervention to reduce the levels of inflammation and oxidative stress. Purpose To examine the effect of a simple dietary antioxidant intervention on levels of inflammation and oxidative stress in persons with metabolic syndrome. Methods A total of 93 individuals with metabolic syndrome (mean age 61 ± 12 years old, 71% female) were enrolled. The intervention group received an 11.5-ounce serving of 100% carotenoid-rich vegetable juice to consume once per day for 30 days. The control group maintained their normal dietary pattern for 30 days. Adherence to the intervention was measured with Veggie Meter®, a validated reflection spectroscopy approach to assess skin carotenoid levels. Inflammation and oxidative stress were measured by plasma levels of high-sensitivity C-reactive protein (CRP) and malondialdehyde (MDA) at baseline and one-month post intervention. Two-way repeated measures analysis of variance was used to compare the group means over time. Log-transformation was applied as necessary for the variables with skewed distribution. Results There was no significant interaction between treatment and time on skin carotenoid levels, (respectively, P=0.214). There was a statistically significant increase of skin carotenoid levels in the intervention group alone (220 vs 264 in pre and post intervention, respectively, P=0.002). Change in mean CRP levels did not differ between control and intervention groups (P=0.520). Similarly, change in mean MDA did not significantly differ between two groups (P = 0.450). Conclusion A simple and easy to adapt, 1-month dietary antioxidant intervention did not change levels of inflammation and oxidative stress in individuals with metabolic syndrome, potentially due to the short-term treatment. Future interventions with dietary antioxidants should be implemented for longer time periods to fully assess the impact on inflammation and oxidative stress.

Mitochondrial Dysfunction Associated with mtDNA in Metabolic Syndrome and Obesity.

Metabolic syndrome (MetS) is a precursor to the major health diseases associated with high mortality in industrialized countries: cardiovascular disease and diabetes. An important component of the pathogenesis of the metabolic syndrome is mitochondrial dysfunction, which is associated with tissue hypoxia, disruption of mitochondrial integrity, increased production of reactive oxygen species, and a decrease in ATP, leading to a chronic inflammatory state that affects tissues and organ systems. The mitochondrial AAA + protease Lon (Lonp1) has a broad spectrum of activities. In addition to its classical function (degradation of misfolded or damaged proteins), enzymatic activity (proteolysis, chaperone activity, mitochondrial DNA (mtDNA)binding) has been demonstrated. At the same time, the spectrum of Lonp1 activity extends to the regulation of cellular processes inside mitochondria, as well as outside mitochondria (nuclear localization). This mitochondrial protease with enzymatic activity may be a promising molecular target for the development of targeted therapy for MetS and its components. The aim of this review is to elucidate the role of mtDNA in the pathogenesis of metabolic syndrome and its components as a key component of mitochondrial dysfunction and to describe the promising and little-studied AAA + LonP1 protease as a potential target in metabolic disorders.

Regulatory Roles of MicroRNAs in the Pathogenesis of Metabolic Syndrome.

Metabolic syndrome refers to a group of several disease conditions together with high glucose triglyceride levels, high blood pressure, lower high-density lipoprotein level, and large waist circumference. About 400 million people worldwide, one-third of the Euro-American population and 27% Chinese population over age 50 have it. microRNAs, an abundant novel class of endogenous small, non-coding RNAs in eukaryotic cells, act as negative controllers of gene expression by promoting either degradation/translational repression of target messenger RNA. More than 2000 microRNAs in the human genome have been identified and they are implicated in various biological & pathophysiological processes, including glucose homeostasis, inflammatory response, and angiogenesis. Destruction of microRNAs has a crucial role in the pathogenesis of obesity, cardiovascular disease, and diabetes. Recently the discovery of circulating microRNAs in human serum may help to promote metabolic crosstalk between organs and serves as a novel approach for the identification of various diseases, like Type 2 diabetes & atherosclerosis. In this review, we will discuss the most recent and up-to-date research on the pathophysiology and histopathology of metabolic syndrome besides their historical background and epidemiological highlight. As well as search the methodologies employed in this field of research and the potential role of microRNAs as novel biomarkers and therapeutic targets for metabolic syndrome in the human body. Furthermore, the significance of microRNAs in promising strategies, like stem cell therapy, which holds enormous promise for regenerative medicine in the treatment of metabolic disorders will also be discussed.

1705-P: Expression of Selected MicroRNAs in Adipose Tissue-Derived Mesenchymal Stem Cells and Metabolic Syndrome

Adipose tissue mesenchymal stem cells (AdMSC) secrete microRNAs (miR). Although miR are involved in pathogenesis of metabolic syndrome, the role of those secreted by AdMSC remains elusive. We aimed to assess expression of selected miR by AdMSC in relation to basic metabolism parameters in nondiabetic adults. For this preliminary study 10 obese, 8 overweight and 5 normal weight subjects with no inflammatory or cancerous disease were enrolled, including 19 female and 6 prediabetic ones. AdMSC were harvested from abdominal subcutaneous fat and cultured in standard conditions. Expressions of four miR reported in metabolic disturbances were estimated with RT-qPCR. Total and visceral fat were assessed with bioimpedance. Expression of miR-21, miR-122, or miR-192 did not correlate with any clinical parameter. On the other hand, expression of miR-155 [2-ΔCt] was lowest in obese subjects (3.69±2.67 vs. 7.07±4.42 in overweight and 10.25±7.05 ×10-3 in normal weight ones, P =0.04, K-W ANOVA). It correlated inversely with BMI, total fat mass, visceral adiposity, and serum CRP, whereas positively (marginally significantly) with serum HDL-cholesterol (table 1). Expression of miR-155 in AdMSC appears blunted in visceral obesity, which correlates with HDL-dyslipidemia and microinflammation. This calls for further study of AdMSC miR secretome in the pathogenesis of metabolic syndrome with focus on miR-155. Disclosure G. Wystrychowski: Other Relationship; Polfa Tarchomin. K. Simka-Lampa: None. A. Witkowska: None. E. Sobecko: None. A. Skubis-Sikora: None. B. Sikora: None. E. Wojtyna: None. K. Gwizdek: None. A. Golda: Other Relationship; Servier Laboratories. M. Wróbel: Other Relationship; Novo Nordisk, Lilly, Boehringer Ingelheim Inc. C. Kruszniewska-Rajs: None. J. Gola: None. Funding Medical University of Silesia, Katowice, Poland

290-OR: FoxK1-Associated Gene Regulatory Network—A New Transcriptional Regulator of Hepatic Insulin Action

Insulin acts on the liver to maintain glucose homeostasis, and disruption of insulin action in liver is central in the pathogenesis of diabetes and metabolic syndrome. While most previous studies of insulin action on gene expression in liver have focused on FoxO1, we have found that Forkhead box protein K1 (FoxK1) is another important regulator of hepatic gene expression which acts in a complementary manner. Thus, upon insulin stimulation, FoxK1 translocates from the cytoplasm to nucleus while FoxO1 translocates from nucleus to cytoplasm. Chromatin immunoprecipitation (ChIP) sequencing shows that FoxK1 binds to &amp;gt;1000 gene regulatory elements in the proximal promoters and enhancers in hepatic chromatin, with TGTTTAC being the major FoxK1 DNA binding motif. De novo motif analysis suggested that HNF4A is also one of the major co-regulators for FoxK1 in mediating gene expression. Insulin stimulated binding of FoxK1 to promoters was observed in up-regulation of genes involved in steroid biosynthesis and cell cycle, and down-regulation of genes involved in autophagy. FoxK1 is also a potential transcription factor for insulin receptor (IRβ) mediated gene regulation as evidenced by its binding to LARS1 and TIMM22 promoters. Both FoxK1 and IRβ share regulation of genes involved in rRNA processing, mitotic cell cycle and nonsense-mediated decay. Interestingly, gene promoters of genes in glucose metabolism (PCK1, G6PC and PKM) are bound by FoxK1, but not by IRβ in response to insulin. FoxK1 can also work with FoxO1 in regulation of genes involved in mitochondrial translation, and with both IRβ and FoxO1 in insulin regulation of AHCY, PPRC1, and CDKN1A, i.e., genes involved in cell senescence, amino acid metabolism and mitochondrial biogenesis. Thus, FoxK1 is a potential factor priming the response to insulin and helps with the recruitment of IRβ or FoxO1 in regulation of gene expression in liver in metabolism and other important biological pathways. Disclosure P.Allu: None. H.Pan: None. J.Dreyfuss: None. C.Kahn: None.

Beneficial effects of seaweed-derived components on metabolic syndrome via gut microbiota modulation.

Metabolic syndrome comprises a group of conditions that collectively increase the risk of abdominal obesity, diabetes, atherosclerosis, cardiovascular diseases, and cancer. Gut microbiota is involved in the pathogenesis of metabolic syndrome, and microbial diversity and function are strongly affected by diet. In recent years, epidemiological evidence has shown that the dietary intake of seaweed can prevent metabolic syndrome via gut microbiota modulation. In this review, we summarize the current in vivo studies that have reported the prevention and treatment of metabolic syndrome via seaweed-derived components by regulating the gut microbiota and the production of short-chain fatty acids. Among the surveyed related articles, animal studies revealed that these bioactive components mainly modulate the gut microbiota by reversing the Firmicutes/Bacteroidetes ratio, increasing the relative abundance of beneficial bacteria, such as Bacteroides, Akkermansia, Lactobacillus, or decreasing the abundance of harmful bacteria, such as Lachnospiraceae, Desulfovibrio, Lachnoclostridium. The regulated microbiota is thought to affect host health by improving gut barrier functions, reducing LPS-induced inflammation or oxidative stress, and increasing bile acid production. Furthermore, these compounds increase the production of short-chain fatty acids and influence glucose and lipid metabolism. Thus, the interaction between the gut microbiota and seaweed-derived bioactive components plays a critical regulatory role in human health, and these compounds have the potential to be used for drug development. However, further animal studies and human clinical trials are required to confirm the functional roles and mechanisms of these components in balancing the gut microbiota and managing host health.

SGK1 Target Genes Involved in Heart and Blood Vessel Functions in PC12 Cells.

Serum and glucocorticoid-regulated kinase 1 (SGK1) is expressed in neuronal cells and involved in the pathogenesis of hypertension and metabolic syndrome, regulation of neuronal function, and depression in the brain. This study aims to identify the cellular mechanisms and signaling pathways of SGK1 in neuronal cells. In this study, the SGK1 inhibitor GSK650394 is used to suppress SGK1 expression in PC12 cells using an in vitro neuroscience research platform. Comparative transcriptomic analysis was performed to investigate the effects of SGK1 inhibition in nervous cells using mRNA sequencing (RNA-seq), differentially expressed genes (DEGs), and gene enrichment analysis. In total, 12,627 genes were identified, including 675 and 2152 DEGs at 48 and 72 h after treatment with GSK650394 in PC12 cells, respectively. Gene enrichment analysis data indicated that SGK1 inhibition-induced DEGs were enriched in 94 and 173 genes associated with vascular development and functional regulation and were validated using real-time PCR, Western blotting, and GEPIA2. Therefore, this study uses RNA-seq, DEG analysis, and GEPIA2 correlation analysis to identify positive candidate genes and signaling pathways regulated by SGK1 in rat nervous cells, which will enable further exploration of the underlying molecular signaling mechanisms of SGK1 and provide new insights into neuromodulation in cardiovascular diseases.

Polymorphisms of Fat Mass and Obesity-Associated Gene in the Pathogenesis of Child and Adolescent Metabolic Syndrome.

Childhood metabolic syndrome (MetS) is prevalent around the world and is associated with a high likelihood of suffering from severe diseases such as cardiovascular disease later in adulthood. MetS is associated with genetic susceptibility that involves gene polymorphisms. The fat mass and obesity-associated gene (FTO) encodes an RNA N6-methyladenosine demethylase that regulates RNA stability and molecular functions. Human FTO contains genetic variants that significantly contribute to the early onset of MetS in children and adolescents. Emerging evidence has also uncovered that FTO polymorphisms in intron 1, such as rs9939609 and rs9930506 polymorphisms, are significantly associated with the development of MetS in children and adolescents. Mechanistic studies reported that FTO polymorphisms lead to aberrant expressions of FTO and the adjacent genes that promote adipogenesis and appetite and reduce steatolysis, satiety, and energy expenditure in the carriers. The present review highlights the recent observations on the key FTO polymorphisms that are associated with child and adolescent MetS with an exploration of the molecular mechanisms underlying the development of increased waist circumference, hypertension, and hyperlipidemia in child and adolescent MetS.

The role of metabolic syndrome in the development of polycystic ovary syndrome in adolescence

The review article presents an analysis of the metabolic syndrome problem in children and adolescents, its role in the development of polycystic ovary syndrome (PCOS) in accordance with the latest International guidelines and modern literature. The urgency of the problem lies in the rapid spread of overweight among children in the world and, consequently, the growth of alimentary-dependent pathology. One of the major consequences of weight problems is metabolic syndrome (MS). There are still no clear MS criteria for children and adolescents. IDF suggests using IDF criteria for adults. Priority in the pathogenesis of MS is given to insulin resistance (IR), which is associated with puberty. The problem of IR assessment remains. HOMA-IR and QUICKI methods are not considered reliable tests to determine IR, so the assessment is based on clinical signs (hyperglycemia, dyslipidemia, abdominal obesity, hypertension). Obesity and IR can be predictors of PCOS, which can often be associated with puberty. Pathological signs of the syndrome typical for adults in adolescence may be a manifestation of the physiological course of puberty. Obligative criteria for the diagnosis of PCOS in adolescence are irregular menstruation/oligomenorrhea, proven biochemically and clinically hyperandrogenemia). First-line therapy for PCOS in adolescents with MS is weight loss and dosed exercise, which helps to normalize a hormonal balance. Drug treatment may include insulin-sensitizing drugs (metformin), antiandrogens (spironlactone, flutamide, cyproterone acetate), 5-alpha-reductase inhibitors (finasteride), combined oral contraceptives, inositol. Prevention of overweight, obesity in children can prevent the development of IR and, accordingly, associated MS and PCOS, reproductive health disorders. Prevention measures are aimed at avoiding maternal obesity, gestational diabetes, malnutrition and smoking during pregnancy, promoting breastfeeding and physical activity.

The Ethnopharmacological Properties of Green-Engineered Metallic Nanoparticles against Metabolic Disorders.

Metabolic syndrome is a multifaceted pathophysiologic condition that is largely caused by an imbalance between caloric intake and energy expenditure. The pathogenesis of metabolic syndrome is determined by an individual's genetic/epigenetics and acquired factors. Natural compounds, notably plant extracts, have antioxidant, anti-inflammatory, and insulin-sensitizing properties and are considered to be a viable option for metabolic disorder treatment due to their low risk of side effects. However, the limited solubility, low bioavailability, and instability of these botanicals hinder their performance. These specific limitations have prompted the need for an efficient system that reduces drug degradation and loss, eliminates unwanted side effects, and boosts drug bioavailability, as well as the percentage of the drug deposited in the target areas. The quest for an enhanced (effective) drug delivery system has led to the formation of green-engineered nanoparticles, which has increased the bioavailability, biodistribution, solubility, and stability of plant-based products. The unification of plant extracts and metallic nanoparticles has helped in the development of new therapeutics against metabolic disorders such as obesity, diabetes mellitus, neurodegenerative disorders, non-alcoholic fatty liver, and cancer. The present review outlines the pathophysiology of metabolic diseases and their cures with plant-based nanomedicine.

Effects of the in-utero dicyclohexyl phthalate and di-n-hexyl phthalate administration on the oxidative stress-induced histopathological changes in the rat liver tissue correlated with serum biochemistry and hematological parameters.

Phthalates are widely used as plasticizers in the industry and are found in cosmetics, food and drink packaging, drugs, toys, households, medical devices, pesticides, personal care products, and paints. Phthalates exert endocrine disrupting and peroxisome proliferator effects in humans and wildlife associated with the pathogenesis of various diseases, including diabetes, obesity, infertility, cardiovascular diseases, metabolic syndrome, and cancer. Since phthalates are metabolized in the liver, which regulates the body's energy metabolism, long or short-term exposure to the phthalates is associated with impaired glucose, lipid, and oxidative stress metabolisms contributing to liver toxicity. However, the impact of in-utero exposure to DHP and DCHP on liver metabolism has not been studied previously. Thus, in this study, we evaluated serum biochemistry parameters, hematological markers, histopathological changes, and oxidative and pentose phosphate pathway (PPP) metabolisms in the liver following in-utero DHP and DCHP administration, respectively, in male and female rats. We found increased relative and absolute liver weights and impaired triglyceride, alanine transaminase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) levels upon dicyclohexyl phthalate (DCHP) and di-n-hexyl phthalate (DHP). Histopathological changes, including congestion, sinusoidal dilatation, inflammatory cell infiltration, cells with a pyknotic nucleus, lysis of hepatocytes, and degeneration of hepatic parenchyma have been observed in the liver samples of DHP and DCHP dose groups. Moreover, increased glutathione s-transferase (GST), glucose 6-phosphate dehydrogenase (G6PD), and glutathione reductase (GR) activities have been found in the liver samples of DHP and DCHP-treated rats associated with impaired pentose phosphate pathway (PPP) and oxidative stress metabolism. First time in the literature, we showed that in-utero exposure to DHP and DCHP causes liver damage associated with impaired oxidative stress metabolism in male and female rats. Our data may guide researchers and governments to regulate and restrict phthalates in industrial products.

Intestinal microbiome characterization of adult Brazilian men with psoriasis compared to omnivore and vegetarian controls

BackgroundPsoriasis is a chronic inflammatory disease associated with systemic inflammation and comorbidities. Changes in the composition of the intestinal microbiome are involved in the pathogenesis of inflammatory diseases and metabolic syndrome. Characterizing the intestinal microbiome of patients with psoriasis may be relevant for the understanding of its clinical course and comorbidity prevention. ObjectiveTo characterize the intestinal microbiome of men with psoriasis compared to omnivore and vegetarian controls (without psoriasis). MethodCross-sectional study of 42 adult males: 21 omnivores with psoriasis; and controls: 14 omnivores and 7 vegetarian individuals. The characterization of the intestinal microbiome was performed by metagenomic analysis. Serum levels of lipopolysaccharide-binding protein (LPB) and C-reactive protein (CRP) were evaluated. ResultsThe groups differed from each other regarding nutritional aspects and microbiome; individuals with psoriasis had a higher consumption of protein and lower consumption of fibers. Levels of LPB, CRP, and the Firmicutes/Bacteroidetes ratio were higher in the group with psoriasis than in the vegetarian group (p<0.05). The genera Prevotella, Mogibacterium, Dorea, Bifidobacterium and Coprococcus, differed in the group with psoriasis compared to vegetarians; the genera Mogibacterium, Collinsella and Desulfovibrio differed from omnivores. A microbiome pattern linked to psoriasis (plsPSO) was identified, which was associated with higher LPB levels (rho=0.39; p=0.02), and lower dietary fiber intake (rho=−0.71; p<0.01). Study limitationsOnly adult men were evaluated. ConclusionA difference was identified in the intestinal microbiome of adult men with psoriasis when compared to healthy omnivores and vegetarian controls. The identified microbiome pattern was correlated with dietary fiber intake and serum levels of LPB.