Search Results (945)

Metagenomic investigation of gut microbiome is a comprehensive and rapid technique for the analysis and diagnosis of numerous diseases. The gut microbiome is an intricate ecosystem, coordinated by the interaction of various microbes and the metabolites produced by them, which helps in developing and sustaining immunity and homeostasis. A healthy gut microbiome is driven by different factors, such as nutrition, lifestyle, etc. The current study examines the association of diet to gut microbiome dysbiosis and its role in various disease conditions. Gut microbiome data was collected from 73 patients and tested at BioAro Inc. lab, using shotgun metagenomics through next generation sequencing. It was then analyzed and compared with data from 20 healthy subjects from HMP database. An in-house bioinformatics pipeline (PanOmiQ) and Pathogen Fast Identifier were utilized for secondary analysis, while tertiary analysis was accomplished using R software. Results showed a higher number of opportunistic pathogen microorganisms in the gut microbiome of subjects consuming a meat diet, as compared to those consuming a plant diet. These opportunistic pathogens included Ruminococcus torques (>3.34%), Ruminococcus gnavus (>2.22%), and Clostridium symbiosum (>1.87%). The study also found a higher relative abundance of these pathogens in cancer patients, as compared to healthy subjects. We also observed a highly significant (p < 0.0001) correlation of a meat diet with obesity in comparison to the subjects on a plant diet and the healthy subjects. Our findings suggest that patients following a plant diet have a lower relative abundance of pathogens that are associated with cancer and obesity. These findings provide critical insight into how we can use shotgun metagenomics to study the composition and diversity of the gut microbiome and the effects of a diet on the gut microbiome and its role in metabolic diseases. This is the first report investigating gut microbiota using shotgun metagenomics, correlating with different diseases and diet followed, which might impact the presence of opportunistic pathogens or keystones species. Additionally, it can provide valuable insights to physicians and dietetic practitioners for providing personalized treatment or customizing a diet plan. Full article

Background/Objective: Insulin resistance (IR) during pregnancy, even in women with normal body mass index (BMI), may affect maternal and fetal metabolic and immune status. This study aimed to evaluate neopterin (NPT), leptin, insulin, and ghrelin concentrations in maternal blood (MB) and umbilical cord blood (CB) in normoglycemic women with and without IR, all with normal BMI. Methods: Peripheral and cord blood was collected from 36 Caucasian women with term, uncomplicated vaginal deliveries. The participants were classified into control (n = 16; age = 30.81 ± 4.875 years) and IR (n = 20; age = 31.95 ± 4.979 years) groups based on a professional medical diagnosis. Anthropometric parameters were recorded, and metabolic/hormonal markers were measured using ELISA and RIA. Results: NPT concentrations in CB were significantly higher in the IR group (p < 0.05), correlated positively with MB NPT levels (r = 0.3809, p < 0.05). A significantly higher concentration of both insulin and leptin was observed in the MB of women with IR compared to the control group (p < 0.0001), whereas in CB, only insulin concentration was significantly higher in the IR group than in healthy controls (p < 0.05). Ghrelin levels did not differ between the groups. Conclusions: Insulin resistance in non-obese pregnant women is associated with increased NPT concentration in CB, which may suggest fetal immune activation. However, defining the role of NTP as a metabolic “messenger” between mother and child requires further study. Full article

Background: Pelemir (Cephalaria syriaca) is a bitter-tasting ancestral legume with a high polyphenol content and emerging potential as a functional food ingredient. This study investigated the acute metabolic effects of pelemir-enriched bread in adults. Methods: In this two-phase non-randomized trial, 60 participants in three groups (n = 20 per group: healthy controls [HCs], individuals with obesity [OB], and individuals with type 2 diabetes [T2D]) consumed regular or pelemir-enriched bread on two separate test days. Postprandial glucose, insulin, C-peptide, GLP-1, PYY, ghrelin, leptin, triglyceride, and IL-6 were measured over 120 min. Subjective appetite ratings were evaluated using visual analog scales (VASs). The incremental area under the curve (iAUC) values were compared using Wilcoxon tests and linear mixed-effects models. Results: Pelemir-enriched bread significantly increased iAUCs for insulin (p = 0.014), C-peptide (p = 0.046), and GLP-1 (p = 0.039) compared to regular bread. There was no significant change in iAUC for glucose. Group-stratified analyses showed a higher postprandial iAUC of glucose, insulin, and C-peptide in the OB group compared to the HC group. VAS-based appetite ratings did not show significant changes in hunger, fullness, or desire to eat, but a borderline significant reduction was observed in prospective food consumption after pelemir-enriched bread (p = 0.050). Conclusions: Acute consumption of pelemir-enriched bread may modulate postprandial insulin and incretin responses. Its modest impact on subjective appetite regulation supports further investigation of pelemir as a functional food rich in polyphenols, especially in populations with metabolic dysfunction. Full article

Background/Objectives: Diet and obesity contribute to approximately 50% of tumor development. Therefore, nutrition plays a key role not only in cancer prevention but also in determining prognosis. Notably, between 30% and 90% of cancer patients experience malnutrition. Furthermore, the hypercatabolic state induced by tumors leads to widespread protein degradation, clinically manifesting as sarcopenia or cachexia, and ultimately accelerating mortality. This narrative review examines the potential role of amino acids (AAs) in inhibiting tumor growth and counteracting protein–energy malnutrition—aiming to preserve muscle mass and nourish healthy cells while placing neoplastic cells in a state of metabolic stress. Methods: The analysis was conducted following the Standards for Reporting Qualitative Research guidelines. Results: Administration of targeted mixtures of essential amino acids (EAAs) has been shown to improve muscle mass, strength, and quality of life in patients with hypercatabolic conditions. Experimental in vitro and in vivo studies also suggest a potential inhibitory effect on tumor proliferation. However, increased availability of certain AAs may, in some cases, stimulate tumor growth, one reason why EAAs supplementation in cancer patients remains controversial. Conclusions: Despite prevailing concerns, emerging evidence indicates that supplementation with a complete, well-balanced EAAs formulation may be a valuable adjunct to standard cancer therapies. This approach could help correct cancer-associated protein imbalances, enhance patients’ quality of life, and create a metabolic environment unfavorable to tumor progression. Full article

The circadian rhythm of the central brain clock in the suprachiasmatic nucleus (SCN) is synchronized by light. White adipose tissue (WAT) is one of the metabolic endocrine organs containing a molecular clock, and it is synchronized by the SCN. Excess WAT is a risk factor for health issues including type 2 diabetes mellitus (DM2). We hypothesized that bright-light exposure would affect the human WAT transcriptome. Therefore, we analyzed WAT biopsies from two previously performed randomized cross-over trials (trial 1: n = 8 lean, healthy men, and trial 2: n = 8 men with obesity and DM2). From 7:30 h onwards, all the participants were exposed to either bright or dim light. Five hours later, we performed a subcutaneous abdominal WAT biopsy. RNA-sequencing results showed major group differences between men with obesity and DM2 and lean, healthy men as well as a differential effect of bright-light exposure. For example, gene sets encoding proteins involved in oxidative phosphorylation or respiratory chain complexes were down-regulated under bright-light conditions in lean, healthy men but up-regulated in men with obesity and DM2. In addition to evident group differences between men with obesity and DM2 and healthy lean subjects, autonomic or neuroendocrine signals resulting from bright-light exposure also differentially affect the WAT transcriptome. Full article

Obesity is a significant health issue, as it is related to human diseases such as asthma and respiratory viral infections. Asthma patients with obesity have more severe diseases, which can be presented with type 1 (e.g., IFN-γ) high inflammation. The interactions of obesity or saturated fatty acids (e.g., palmitic acid, PA) with IFN-γ in airway viral infections have not been clear. In this study, we determined the role of obesity risk factors high-fat diet (HFD) and PA in rhinovirus infection in the context of IFN-γ stimulation in mice and cultured human tracheobronchial epithelial cells. We further examined the therapeutic effect of a glycolytic inhibitor on metabolic reprogramming and viral infection in our experimental models. In mice, HFD in combination with IFN-γ significantly increased lung rhinovirus levels as well as neutrophilic inflammation. Similarly, PA and IFN-γ combination increased viral infection in mice, but HFD or PA alone had a minimal effect on viral infection. Mouse model data were confirmed in cultured primary healthy human airway epithelial cells where PA and IFN-γ together increased viral load. Mechanistically, HFD or PA in combination with IFN-γ up-regulated the glycolytic pathway and generated metabolites favoring viral replication. Inhibition of glycolysis by 2-DG effectively reduced viral infection in human airway epithelial cells. Our data suggest that hosts with obesity along with type 1 high inflammation may be at an increased risk of respiratory viral infections. Intervention of the glycolytic pathway or its metabolites may reduce the severity of viral infection. Full article

Metabolically healthy (MHO) and unhealthy obesity (MUO) exhibit distinct molecular genetic mechanisms underlying metabolic disorders. Studying gene and microRNA expression in subcutaneous adipose tissue (SAT) may reveal key pathogenetic differences between these phenotypes. We compared the expression of genes (ADIPOQ, HIF1A, CCL2) and microRNAs (miR-142-3p, miR-155, miR-378) in SAT between MHO and MUO patients and assessed their association with metabolic parameters. The study included 39 obese patients (19 MHO, 20 MUO) and 10 healthy controls. SAT biopsies were analyzed using real-time PCR. Correlations with clinical and metabolic markers were evaluated. Obese patients showed decreased ADIPOQ (p = 0.039) and miR-142 (p = 0.008) expression and increased CCL2 (p = 0.004), miR-155 (p = 0.017), and miR-378 (p = 0.04) expression compared to the controls. MUO patients exhibited higher HIF1A expression (p = 0.03) and strong correlations between CCL2 and dyslipidemia (total cholesterol, triglycerides)/dysglycemia (fasting glucose) (r = 0.45, p = 0.03; r = 0.52, p = 0.01; r = 0.63, p = 0.001, respectively). miR-142 negatively correlated with fibrosis markers, while miR-378 was linked to insulin resistance. The differential gene and microRNA expression highlights the role of inflammation, hypoxia, and fibrosis in MUO pathogenesis. miR-142-3p, miR-155, and miR-378 may serve as potential biomarkers for metabolic risk stratification and therapeutic targets. Full article

Some reports indicated the association of rs17602729 and rs34526199 functional polymorphisms of the AMPD1 gene encoding adenosine monophosphate deaminase 1 (AMPD1) with the risk of coronary artery disease (CAD) and/or its intermediate phenotype. Therefore, the aim of our study was to analyze the association of both AMPD1 polymorphisms with the predisposition to disease and both clinical and biochemical phenotypes but solely in diabetic individuals with CAD. The study group consisted of 196 adult diabetic individuals with CAD, and the control group comprised 200 healthy newborns. Both AMPD1 polymorphisms were identified by a SNaPshot minisequencing reaction. Clinical and laboratory data were taken from patients’ records. There were no significant differences between both groups in the frequency distributions of AMPD1:rs17602729 and rs34526199 alleles or genotypes. BMI and the frequency of obesity in TT rs17602729 homozygotes (no AMPD1 activity) were significantly lower and the serum concentration of HDL cholesterol was significantly higher compared to other patients. The concentrations of total cholesterol and LDL cholesterol in homozygotes for wild-type AMPD1:rs17602729 (c.34C) and rs34526199 (c.860A) alleles (full AMPD1 activity) were significantly lower compared to its values in other patients. Our results suggest that genetically predicted activity of AMPD1 is associated with variation in body mass and lipid metabolism in diabetic Polish people with CAD. Full article

Liver sinusoidal endothelial cells (LSECs) are essential for preserving liver homeostasis. Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a category of hepatic disorders characterized by excessive fat accumulation in the liver, known as steatosis. Over time, accumulated hepatic fat can induce inflammation of the liver (hepatitis). MASLD is among the most prevalent types of chronic liver disease. Obesity and Type 2 diabetes mellitus (T2DM) are frequent etiological factors of MASLD. In the absence of therapy, MASLD can lead to more severe hepatic conditions, which can be life-threatening. MASLD is noteworthy due to its potential progression to MASH and further severe liver impairment, including cirrhosis and hepatocellular carcinoma (HCC), a neoplastic progression. This narrative review examines the distinctive functions of LSECs in regulating immunologic responses, collagenization, and drug-sensitive bioreactivity in healthy livers, MASLD, and metabolic dysfunction-associated steatohepatitis (MASH), as well as in a human primary 3D model. We found that LSECs serve as crucial regulators of immunological equilibrium in the liver by inhibiting disproportionate immunologic activation, concurrently filtering tissue antigens, and engaging with immunologic cells, such as Kupffer cells (KCs) and T lymphocytes. In chronic diseases of the liver, LSECs experience cellular dysfunction, resulting in capillarization (focal to diffuse), loss of fenestrations (fenestrae), and the activation of pro-fibrotic signaling pathways, including transforming growth factor-beta (TGF-β). Indeed, TGF-β is crucial in activating hepatic stellate cells (HSCs), a process that facilitates the progression of liver disease toward fibrosis. In addition to examining the dynamic interplay between LSECs, specifically HSCs, and other liver cells throughout the progression of fatty liver–MASH, we suggest that LSECs may become a potential therapeutic target for modifying immune responses and averting fibrosis in hepatic disorders. The limitations of animal models are also highlighted and discussed. Full article

Obesity affects millions of individuals globally, and a deeper understanding of its associated physiological disturbances is essential for addressing key public health concerns. It has been demonstrated that the influenza virus possesses substantial global epidemic potential, with higher incidence rates observed in obese individuals and prolonged recovery times. Obese individuals exhibit impaired immune organ function, decreased immune cell activity, disrupted metabolism characterized by mitochondrial dysfunction, and an imbalance in gut microbiota associated with intestinal mucosal barrier damage. The gut microbiota and their metabolic composition in obese patients differ from those in non-obese individuals, potentially promoting viral replication and exacerbating disease severity. These factors collectively contribute to more severe tissue damage and heightened immune responses in obese patients during influenza infection. Therefore, understanding the impact of obesity on influenza virus infection dynamics enables the development of strategies promoting healthy lifestyles to manage body weight and enhance immunity against viral infections. Additionally, given that this special population may not respond optimally to antimicrobial drugs and vaccination, it is necessary to consider how treatment strategies for this group are managed. This review illustrates findings concerning the impact of obesity on the immune response to influenza virus infection, including potential underlying mechanisms. Full article

Background and objectives: Overweight and obesity are global public health problems, as they increase the risk of chronic diseases, reduce quality of life, and generate a significant economic and healthcare burden. This study evaluates the capacity of nutritional patterns and psychological status to predict the presence of cardiometabolic risk among overweight and obese young adults, from a neural network approach. Method: The study included N = 188 overweight or obese students, who provided measures on their dietary intake, physical and psychological state, and sociodemographic profile. Neural networks were used to predict their metabolic status, classified into two categories based on anthropometric, biochemical, and cardiometabolic risk factors: metabolically unhealthy obesity (MUO) versus metabolically healthy obesity (MHO). Results: The predictive models demonstrated differences in specificity and sensitivity capacity depending on the criteria employed for the classification of MUO/MHO and gender. Among the female subsample, MUO was predicted by poor diet (low consumption of mineral and vitamins, and high consumption of fats and sodium) and high levels of depression and stress, while among the male subsample high body mass index (BMI), depression, and anxiety were the key factors. Protective factors associated to MHO were lower BMI, lower psychopathology distress and more balanced diets. Predictive models based on the HOMA-IR criterion yielded very high specificity and low sensibility (high capacity to identify MHO but low accuracy to identify MUO). The models based on the IDF criterion achieved excellent discriminative capacity for men (specificity and sensitivity around 92.5%), while the model for women obtained excellent sensitivity and low specificity. Conclusions: The results provide empirical support for personalized prevention and treatment programs, accounting for individual differences with the aim of promoting healthy habits among young adults, especially during university education. Full article

Background/Objectives: Cardiovascular disease (CVD) remains one of the leading causes of death worldwide, with several well-established risk factors. Among dermatological conditions, psoriasis is a well-known contributor to cardiometabolic risk, while lichen planus (LP) remains an underexplored chronic inflammatory disorder in this context. This study aimed to comparatively assess the prevalence and clinical patterns of metabolic syndrome (MetS) components in patients with LP versus psoriasis and healthy controls, focusing on the intrinsic inflammatory burden in patients not receiving systemic therapy. We also examined whether specific clinical subtypes of LP carry distinct metabolic profiles. Methods: We conducted a cross-sectional observational study at a tertiary dermatology center between January 2020 and December 2024. A total of 236 adult patients were included: 78 with LP, 79 with psoriasis, and 79 controls with minor dermatological conditions. Demographic, clinical, and laboratory data were collected. LP subtypes (cutaneous, mucocutaneous, reticular oral, erosive oral) were evaluated using the Lichen Planus Activity Index (LPAI) and Oral Lichen Planus Clinical Index (OLP-CI); psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI). Cardiometabolic comorbidities were assessed according to established guidelines. Results: LP patients showed significantly higher prevalence of hypertension (OR 1.94, p = 0.044) and type 2 diabetes mellitus (OR 3.09, p = 0.015) compared to controls. Compared to psoriasis, LP was associated with a higher prevalence of mixed dyslipidemia (OR 3.41, p = 0.033), while psoriasis showed more abdominal obesity (OR 0.35, p = 0.003). Mucosal LP subtypes, especially erosive and reticular oral LP, were linked to elevated cardiometabolic risk. Conclusions: LP, particularly its oral subtypes, is associated with a distinct cardiometabolic risk profile comparable to or exceeding that of psoriasis. These findings support the need for systematic metabolic screening in LP patients as part of comprehensive care. Full article

Background/Objectives: Maternal nutrition and pregestational BMI are critical determinants of pregnancy outcomes. This prospective multicenter observational study investigated the interplay between prepregnancy BMI, dietary patterns, and oxidative/inflammatory status in 153 Italian healthy pregnant women with normal weight (NW), overweight (OW), or obesity (OB). Methods: Detailed clinical, biochemical, placental, and neonatal data were measured at third trimester and delivery. Dietary intake was assessed via a validated questionnaire, and dietary patterns were derived using principal component analysis. Results: OW and OB women had significantly higher levels of inflammatory (CRP, hepcidin) and oxidative stress biomarkers (DNA/RNA damage, catalase activity) than NW. Multivariate models confirmed independent associations between BMI and these biomarkers (CRP: β = 0.297, p = 0.000; hepcidin: β = 1.419, p = 0.006; DNA/RNA damage: β = 409.9, p = 0.000; catalase activity: β = 1.536, p = 0.000). Superoxide dismutase activity and total antioxidant capacity were not associated with BMI. Nutritional intake across BMI groups was largely suboptimal relative to national recommendations, with insufficient levels of polyunsaturated fats and key micronutrients. Four dietary patterns were identified, with adherence varying by BMI. A “prudent-style” pattern (high plant, low animal) was positively associated with gestational age (β = 0.243, p = 0.033) and inversely with neonatal head circumference (β = −0.414, p = 0.050). A “Western-like” pattern (high sugars, snacks, animal fats) was linked to reduced maternal ferritin (β = −2.093, p = 0.036) and increased neonatal head circumference (β = 0.403, p = 0.036). However, not all deviations from the “prudent-style” pattern were metabolically equivalent: while Pattern 3 (high-protein, carbohydrate) may offer partial protective effects, Pattern 4 (moderate protein/plant/sugar) displayed elements of nutritional imbalance with signs of placental inefficiency (β = −0.384, p = 0.023). Conclusions: These findings underscore the dual impact of maternal BMI and diet quality on oxidative-inflammatory balance and perinatal outcomes, supporting the need for early, individualized nutritional strategies in pregnancy. This is further emphasized by the variability in dietary adherence across BMI categories. Full article

Background: Clinical outcomes among older adults hospitalized with heart failure with preserved ejection fraction (HFpEF) in the setting of metabolically healthy obesity (MHO) remain insufficiently explored. This study aimed to evaluate whether MHO status is associated with different rates of major adverse cardiac and cerebrovascular events (MACCEs) during HFpEF-related hospitalizations compared to patients without MHO. Methods: Data from the 2019 National Inpatient Sample (NIS) database was analyzed using relevant ICD-10 codes to identify HFpEF admissions in older adults. Propensity score matching (1:1) was applied to generate balanced cohorts of patients with and without MHO. Multivariable adjustments were performed to assess primary outcomes, including MACCEs, all-cause mortality (ACM), acute myocardial infarction (AMI), dysrhythmia, cardiac arrest (CA), and stroke. Statistical significance was set at p < 0.05. Results: Each MHO cohort included 22,405 patients with a median age of 75 years. The MHO+ group demonstrated a significantly higher risk of dysrhythmia (OR 1.32, 95% CI 1.21–1.43, p < 0.001). Interestingly, an “obesity paradox” was observed, as the MHO+ cohort had lower odds of MACCEs (OR 0.70, 95% CI 0.61–0.81, p < 0.001), ACM (OR 0.66, 95% CI 0.54–0.82, p < 0.001), and AMI (OR 0.71, 95% CI 0.59–0.86, p = 0.001) compared to MHO−. No significant differences were found for CA or stroke between the groups. Conclusions: Although the MHO+ group had an elevated risk of dysrhythmia, they exhibited more favorable outcomes in terms of MACCEs, ACM, and AMI—supporting the concept of an “obesity paradox.” Further research is needed to better understand the role of MHO as a comorbid condition in patients with HFpEF. Full article

A dietary supplement, trans-resveratrol and hesperetin (tRES+HESP)—also known as GlucoRegulate—induces increased expression of glyoxalase 1 (Glo1) by activation of transcription factor Nrf2, countering accumulation of the reactive dicarbonyl glycating agent, methylglyoxal. tRES+HESP corrected insulin resistance and decreased fasting and postprandial plasma glucose and low-grade inflammation in overweight and obese subjects in a clinical trial. The aim of this study was to explore, for the first time, health-beneficial gene expression other than Glo1 induced by tRES+HESP in human endothelial cells and fibroblasts in primary culture and HepG2 hepatoma cell line and activity of cis-resveratrol (cRES) as a Glo1 inducer. We measured antioxidant response element-linked gene expression in these cells in response to 5 µM tRES+HESP by the NanoString method. tRES+HESP increases gene expression linked to the prevention of dicarbonyl stress, lipid peroxidation, oxidative stress, proteotoxicity and hyperglycemia-linked glycolytic overload. Downstream benefits were improved regulation of glucose and lipid metabolism and decreased inflammation, extracellular matrix remodeling and senescence markers. The median effective concentration of tRES was ninefold lower than cRES in the Glo1 inducer luciferase reporter assay. The GlucoRegulate supplement provides a new treatment option for the prevention of type 2 diabetes and metabolic dysfunction–associated steatotic liver disease and supports healthy aging. Full article