Metabolic Disorders Research Articles

Sestrin2 serves as a scaffold protein to maintain cardiac energy and metabolic homeostasis during pathological stress.

Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide. Metabolic imbalances and pathological stress often contribute to increased mortality. Sestrin2 (Sesn2) is a stress-inducible protein crucial in maintaining cardiac energy and metabolic homeostasis under pathological conditions. Sesn2 is upregulated in response to various stressors, including oxidative stress, hypoxia, and energy depletion, and mediates multiple cellular pathways to enhance antioxidant defenses, promote autophagy, and inhibit inflammation. This review explores the mechanisms through which Sesn2 regulates these pathways, focusing on the AMPK-mTORC1, Sesn2-Nrf2, and HIF1α-Sesn2 pathways, among others. We can identify the potential therapeutic targets for treating CVDs and related metabolic disorders by comprehending these complex mechanisms. Sesn2's unique ability to respond thoroughly to metabolic challenges, oxidative stress, and inflammation makes it a promising prospect for enhancing cardiac health and resilience against pathological stress.

The Role of Gut Microbioma in Human Health: Exploring the Impact on Metabolism, Immunity, and Neurological Disorders

Abstract: The human microbiota has been progressively accepted for its role in sustaining overall health and well-being. The gut microflora vigorously communicates with the host metabolic system that exert influence on the progression, maturation, immune cells development and immune homeostasis maintenance. For the proper functioning of the immune system a diversified and steady gut microflora is needed, while “Dysbiosis” or an imbalance in the gut microbioma will lead to autoimmune and inflammatory diseases. The gut microbiota provides shape to our immune response and contribute to host protection against pathogen or bacterium through mechanisms such as the transformation of pro- inflammatory cytokine production, regulatory T-cell inductor and by intestinal mucosaql barrier. In addition to gut microbiota can affect our neurological function and play a key role in the pathogenesis of psychological disorders such as autism, depression, anxiety, Parkinson and Alzheimer’s disease. Gut microbiota can regulate neurological disorders by supplementing them with fecal transplantation, probiotics and antibiotics. An important parameter to consider gut microbioma disorder is Firmicutes/ Bacteroidetes.

In-vitro evaluation of antioxidant properties of aqueous extracts of Murraya koenigii, Aegle marmelos and Laurus nobilis

This study investigates the antioxidant properties of aqueous extracts of Murraya koenigii (curry leaf), Aegle marmelos (bael) and Laurus nobilis (bay leaf) using in vitro assays. The plants have been traditionally used in Indian medicinal systems for the treatment of various metabolic disorders. Aqueous extracts from the leaves of Murraya koenigii, fruit pulp of Aegle marmelos and leaves of Laurus nobilis were prepared. The total phenolic content and total flavanoid content was also determined in these aqueous extracts. They were tested for their ability to scavange free radicals by DPPH assay, ABTS assay and FRAP assay which are elevated during various metabolic disorders. The results suggest that all the three plants exhibited significant antioxidant activities. But strongest antioxidant properties were exhibited by Murraya koenigii leaf extract followed by the pulp of Aegle marmelos and lowest antioxidant activity was exhibited by Laurus nobilis extract, supporting their use in traditional medicine and potential development into therapeutic agents. So, this research suggested that these medicinal plants possess a significant antioxidant potential and are important source of natural antioxidants and can be effectively used in treating oxidative stress disorders. As a result, the study's significant findings demonstrate that it is a step towards evidence-based phytomedicine.

The association of osteoarthritis with metabolic disorders

Osteoarthritis (OA) is the most common form of synovial joint arthritis that causes chronic pain and disability to a large number of people worldwide. Most often, osteoarthritis affects the joints of the knees, hips, spine and hands. The Global Burden of Disease (GBD, 2021) estimates that osteoarthritis will be the fourth leading cause of disability by 2030, with enormous healthcare costs for treatment, as well as significant indirect costs due to loss of productivity and premature retirement. The aim of our research is to determine in what way prevalent metabolic syndrome is among participants with osteoarthritis of one of the synovial joints (knees, hips, hands), and whether metabolic disorders are a risk factor for the development and worsening of osteoarthritis. A prospective clinical study was conducted at the Public Health Institution Health Center Živinice, from July 2022 to May 2024, on a random sample of 200 participants with a confirmed clinical diagnosis of osteoarthritis (OA), who were divided into a group with metabolic syndrome and a group without metabolic syndrome based on the NCEP ATP III panel criteria for metabolic syndrome. The prevalence of knee osteoarthritis is significantly higher compared to the prevalence of hip and hand osteoarthritis, and it is greater among participants with a higher BMI (in participants with the highest BMI, knee osteoarthritis occurs with a 100% probability) and with the presence of metabolic syndrome, especially in more severe forms, specifically radiologically confirmed osteoarthritis, regardless of age and gender. Unlike OA knees the prevalence of OA hips and hands shows no correlation with BMI and metabolic syndrome. Multiple comparative analysis of differences in the average severity of osteoarthritis of the knee of subjects with normal glycemia / prediabetes / diabetes type 2 it showed a statistically significant difference in the average severity of knee osteoarthritis in subjects with regular blood sugar compared to subjects with prediabetes/diabetes mellitus type 2 regardless of age and gender. This means that with an increase in blood sugar levels, the degree of severity of osteoarthritis of the knee increases, since each subsequent Group has a higher average value of this indicator (p<0.05; CI 95%).

The effect of Xerostomia in diabetes mellitus patients on the incidence of dry socket after tooth extraction: A literature review

Background: Diabetes Mellitus (DM) is a metabolic disorder caused by the absence of insulin hormone production or lack of response to insulin. Diabetes mellitus can cause complications such as caries, periodontal disease, and xerostomia. Xerostomia is associated with low salivary flow which can cause several additional complications. Objective: To determine the effect of xerostomia, a complication in patients with diabetes mellitus, on the incidence of dry sockets after tooth extraction. Method: The method used in this study is a Literature Review, which searches three different journal databases, using the search terms "xerostomia" OR "diabetes mellitus" AND "tooth extraction" OR "dry socket." Results: It shows that there is an effect between the occurrence of xerostomia in patients with diabetes mellitus and the incidence of dry sockets after tooth extraction. Discussion: In patients with diabetes mellitus, saliva production can decrease due to nerve and blood vessel damage caused by glucose metabolism disorders in the body. This can reduce the quality and increase the viscosity of saliva, making the wound-healing process after tooth extraction more difficult. Xerostomia in patients with diabetes mellitus can worsen the dry socket condition because of the lack of moisture in the oral cavity, which can affect the blood clotting process after tooth extraction. If the blood clot dislodges, it can cause a dry socket in xerostomia patients. Conclusion: Dry socket in diabetic patients with xerostomia is thought to be due to low saliva production which interferes with wound healing after tooth extraction.

The role of metformin in modulating cardiometabolic risk in obese pediatric populations with metabolic syndrome: A systematic review

Introduction: Obesity significantly increases the risk of developing cardiometabolic complications, which are precursors to cardiovascular diseases (CVD). In children and adolescents, metabolic dysfunctions such as insulin resistance, dyslipidemia, and hypertension are key contributors to early-onset cardiovascular risk. Metformin, a well-established antidiabetic agent, has shown potential benefits in addressing these metabolic imbalances. However, the long-term impact of metformin on cardiovascular outcomes in obese pediatric patients remains unclear. Aim: This systematic review aims to evaluate the effect of metformin on cardiometabolic parameters in obese children and adolescents with metabolic syndrome, focusing on insulin sensitivity, body mass index (BMI), blood pressure, and lipid profiles. Methods: A systematic review was conducted by searching databases including PubMed, Cochrane Library, Embase, and Web of Science. The inclusion criteria targeted randomized controlled trials (RCTs), cohort studies, systematic reviews, and meta-analyses published between 2004 and 2024. Pediatric patients aged 6-18 years with obesity and metabolic syndrome were included. The primary outcomes assessed were BMI, insulin sensitivity, lipid profiles, blood pressure, and cardiovascular outcomes. Results: A total of 23 studies, including 10 RCTs and 1 meta-analysis, were reviewed, involving 777 patients. Metformin demonstrated consistent improvements in insulin sensitivity and BMI in obese children and adolescents. Several studies reported modest reductions in BMI, improved insulin resistance, and better lipid profiles. However, variability in results was observed regarding long-term cardiovascular outcomes. While metformin reduced systolic blood pressure and carotid intimal-medial thickness (CIMT), the long-term impact on preventing major cardiovascular events remained inconclusive. Discussion: Metformin’s benefits on cardiometabolic risk factors in obese children are primarily attributed to its effects on insulin sensitivity, lipid metabolism, and inflammatory pathways. Its ability to activate AMP-activated protein kinase (AMPK) leads to improved metabolic profiles and reduced inflammation and is crucial for mitigating obesity-related cardiovascular risks. Despite these positive effects, the evidence for long-term prevention of cardiovascular events is limited and requires further exploration. Conclusions: Metformin offers significant short-term benefits in improving BMI, insulin sensitivity, and cardiometabolic parameters in obese children and adolescents. However, its long-term efficacy in preventing cardiovascular events remains uncertain. Further studies are necessary to establish its role in long-term cardiovascular protection in pediatric populations

Combi-Elastography versus Transient Elastography for Assessing the Histological Severity of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Combi-elastography is a B-mode ultrasound-based method in which two elastography modalities are utilized simultaneously to assess metabolic dysfunction-associated steatotic liver disease (MASLD). However, the performance of combi-elastography for diagnosing metabolic dysfunction-associated steatohepatitis (MASH) and determining fibrosis severity is unclear. This study compared the diagnostic performances of combi-elastography and vibration-controlled transient elastography (VCTE) for identifying hepatic steatosis, fibrosis, and high-risk MASH. Participants who underwent combi-elastography, VCTE, and liver biopsy were selected from a prospective cohort of patients with clinically suspected MASLD. Combi-elastography-related parameters were acquired, and their performances were evaluated using area under the receiver-operating characteristic curve (AUROC) analysis. A total of 212 participants were included. The diagnostic performance for hepatic steatosis of the attenuation coefficient adjusted by covariates from combi-elastography was comparable to that of the controlled attenuation parameter measured by VCTE (AUROC, 0.85 vs 0.85; p=0.925). The performance of the combi-elastography-derived fibrosis index adjusted by covariates for diagnosing significant fibrosis was comparable to that of liver stiffness measured by VCTE (AUROC, 0.77 vs 0.80; p=0.573). The activity index from combi-elastography adjusted by covariates was equivalent to the FibroScan-aspartate aminotransferase score in diagnosing high-risk MASH among participants with MASLD (AUROC, 0.72 vs 0.74; p=0.792). The performance of combi-elastography is similar to that of VCTE when evaluating histology of MASLD.

Small hepatitis B virus surface antigen (SHBs) induces dyslipidemia by suppressing apolipoprotein-AII expression through ER stress-mediated modulation of HNF4α and C/EBPγ.

Persistent infection with hepatitis B virus (HBV) often leads to disruptions in lipid metabolism. Apolipoprotein AII (apoAII) plays a crucial role in lipid metabolism and is implicated in various metabolic disorders. However, whether HBV could regulate apoAII and contribute to HBV-related dyslipidemia and the underlying mechanism remain unclear. This study revealed significant reductions in apoAII expression in HBV-expressing cell lines, the serum, and liver tissues of HBV-transgenic mice. The impact of HBV on apoAII is related to small hepatitis B virus surface antigen (SHBs). Overexpression of SHBs decreased apoAII levels in SHBs-expressing hepatoma cells, transgenic mice, and the serum of HBV-infected patients, whereas suppression of SHBs increased apoAII expression. Mechanistic investigations demonstrated that SHBs repressed the apoAII promoter activity through a HNF4α- and C/EBPγ-dependent manner; SHBs simultaneously upregulated C/EBPγ and downregulated HNF4α by inhibiting the PI3K/AKT signaling pathway through activating endoplasmic reticulum (ER) stress. Serum lipid profile assessments revealed notable decreases in high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) in SHBs-transgenic mice compared to control mice. However, concurrent overexpression of apoAII in these mice effectively counteracted these reductions in lipid levels. In HBV patients, SHBs levels were negatively correlated with serum levels of HDL-C, LDL-C, TC, and TG, whereas apoAII levels positively correlated with lipid content. This study underscores that SHBs contributes to dyslipidemia by suppressing the PI3K/AKT pathway via inducing ER stress, leading to altered expression of HNF4α and C/EBPγ, and subsequently reducing apoAII expression.IMPORTANCEThe significance of this study lies in its comprehensive examination of how the hepatitis B virus (HBV), specifically through its small hepatitis B virus surface antigen (SHBs), impacts lipid metabolism-a key aspect often disrupted by chronic HBV infection. By elucidating the role of SHBs in regulating apolipoprotein AII (apoAII), a critical player in lipid processes and associated metabolic disorders, this research provides insights into the molecular pathways contributing to HBV-related dyslipidemia. Discovering that SHBs downregulates apoAII through mechanisms involving the repression of the apoAII promoter via HNF4α and C/EBPγ, and the modulation of the PI3K/AKT signaling pathway via endoplasmic reticulum (ER) stress, adds critical knowledge to HBV pathogenesis. The research also shows an inverse correlation between SHBs expression and key lipid markers in HBV-infected individuals, suggesting that apoAII overexpression could counteract the lipid-altering effects of SHBs, offering new avenues for understanding and managing the metabolic implications of HBV infection.

Drug treatment for MASLD: Progress and direction.

Metabolic dysfunction-associated steatotic liver disease (MASLD), also called non-alcoholic fatty liver disease, is the most epidemic chronic liver disease worldwide. Metabolic dysfunction-associated steatohepatitis (MASH) is the critical stage of MASLD, and early diagnosis and treatment of MASH are crucial for reducing the incidence of intrahepatic and extrahepatic complications. So far, pharmacotherapeutics for the treatment of MASH are still a major challenge, because of the complexity of the pathogenesis and heterogeneity of MASH. Many agents under investigation have shown impressive therapeutic effects by targeting different key pathways, including the attenuation of steatohepatitis or fibrosis or both. It is notable that thyroid hormone receptor-β agonist, resmetirom has become the first officially approved drug for treating MASH with fibrosis. Other agents such as peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 analogs, and fibroblast growth factor 21 analogs are awaiting approval. This review focuses on the current status of drug therapy for MASH and summarizes the latest results of new medications that have completed phase 2 or 3 clinical trials, and presents the future directions and difficulties of new drug research for MASH.

Saturated Fats: Time to Assess Their Beneficial Role in a Healthful Diet

Saturated fats are widely seen as undesirable components of a healthy diet, as a result of their illusory association with elevated serum cholesterol. The regulation of serum cholesterol is now better understood and a lack of polyunsaturated fatty acids, rather than an abundance of saturated fatty acids, is responsible. Palmitic acid was shown to incite inflammation at unnaturally high concentrations in tissue culture, but later was found to play an auxiliary role as a precursor to ceramide biosynthesis and possibly in the palmitoylation of membrane receptors involved in the initiation of inflammation. Studies of arthritic inflammation in lab animals showed that dietary saturated fats are anti-inflammatory, whereas polyunsaturated oils are pro-inflammatory. Inflammation plays a role in numerous metabolic diseases, including insulin resistance, fatty liver disease and metabolic syndrome, among others. Fat, as triglycerides in adipose tissue, is an efficient way for living organisms to store energy and reduce the toxicity of other macronutrients. Macronutrients, such as excess carbohydrates and polyunsaturated fatty acids, are converted to saturated and monounsaturated fatty acids for storage as triglycerides in adipose tissue. Fatty acids are released from adipose tissue during fasting and as a result of some metabolic disorders, where elevated levels of nonesterified fatty acids in blood can lead to hepatic lipid accumulation, inflammation and insulin resistance. Although most serum nonesterified fatty acids may be saturated fatty acids, they are not necessarily derived from the diet. This paper will attempt to clarify the role of saturated fatty acids, and palmitic acid in particular, with regard to certain adverse health conditions.

Association of metabolic phenotypes with cardiovascular events in primary and secondary prevention

Abstract Background Metabolic disorders are established risk factors for the development of coronary artery disease (CAD) and major adverse cardiovascular events (MACE). Although obesity is strongly related with the metabolic health status, its role as a cardiovascular risk modifier in the absence of metabolic disorders remains controversial. Recent implementation of nutrient-stimulated hormone-based therapies (NUSH) including glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of obesity even in metabolically healthy individuals requires further understanding to ensure optimal patient management. Purpose The aim of this study is to investigate the association of metabolic phenotypes with cardiovascular events in primary and secondary prevention of CAD. Methods We included patients over 18 years electively evaluated for CAD by invasive coronary angiography (ICA) between 2010 and 2021 in our tertiary referral centre in one of Europe’s largest university hospitals. Metabolic disorder was considered as the presence of diabetes, irrespective of additional risk factors, or hypertension and hyperlipidaemia, and obesity as a BMI of ≥30 kg/m², distinguishing four metabolic phenotypes: metabolically healthy/unhealthy nonobese/obese (MHN, MHO, MUN, MUO). The primary study endpoint MACE was defined as a composite of cardiovascular death, non-fatal myocardial infarction, ischemic stroke, and hospitalization for heart failure. Results The total study population included 12 760 patients (68 [58-76] years; 57.3% male), of whom 56.5% presented metabolically healthy (43.3% MHN; 13.1% MHO) and 43.5% unhealthy (28.3% MUN; 15.2% MUO). During a median follow up time of 3.91 (1.75-7.09) years, 2 592 (20.3%) MACE and 3 351 (26.3%) all-cause deaths occurred. Cox regression analysis adjusted for age, sex, and chronic kidney disease (CKD) showed different risk patterns for distinct metabolic phenotypes (Table 1). While we observed higher event rates in metabolically unhealthy compared to healthy individuals, obesity alone was not associated with increased events (Figure 1). However, metabolically healthy individuals experienced lower event rates with increasing BMI. Among patients without or with nonobstructive CAD, metabolic disease was strongly associated with increased subsequent coronary revascularization regardless of BMI. These patterns were similar across all endpoints irrespective of presence of obstructive or nonobstructive CAD. Conclusions Whereas metabolic disorders are strongly associated with adverse clinical events, obesity alone does not reflect the cardiovascular risk profile in patients with or without obstructive CAD. Thus, focusing on obesity alone for primary or secondary prevention appears unjustified. Particularly after the recent implementation of GLP-1 receptor agonists for the treatment of obesity, precise and individual risk stratification is essential to allow for an optimal personalized patient management.Figure 1Table 1

Macrophage heterogeneity in cardiometabolic disease

Abstract Metabolic diseases such as obesity and atherosclerosis are characterised by chronic inflammation that leads to the accumulation of immune cells in affected organs. Macrophages in the obese adipose tissue and the atherosclerotic plaque show transcriptional, phenotypic and functional heterogeneity. The accumulation of CD11c+ macrophages in atherosclerosis and obesity suggests the presence of conserved macrophage phenotypes in metabolic tissues. We aimed to characterise shared and distinct features of monocytes and macrophages in the aorta and adipose tissue in the context of metabolic disease using single-cell techniques. Single-cell RNA sequencing of the blood, aorta and visceral adipose tissue during a time course of metabolic disease progression (steady state, 12w western diet, 18w western diet) and data integration with murine aortic and adipose tissue community datasets revealed conserved and tissue specific features of metabolic disease. Resident macrophages in the aorta and adipose tissue displayed tissue specific transcriptional programs, highlighting that cell maintenance and function of tissue resident macrophages differ between metabolic tissues. Further, macrophages in the aorta and adipose tissue undergo disease associated compositional changes. For example, we uncovered distinct CD11c+ macrophage subsets that are conserved in the aorta and adipose tissue across multiple metabolic disease models and share core transcriptional signatures between both metabolic tissues. However, CD11c+ macrophage subsets showed tissue specific dynamics during metabolic disease progression. Overall, our analysis underscores that tissue niche affects macrophage composition as well as activation and transcriptional regulation patterns. Understanding similarities and differences between the two tissues will be important to inform identification of new therapeutic targets for cardiometabolic diseases.

(Multi-) omics studies of ILC2s in inflammation and metabolic diseases

Type 2 innate lymphoid cells (ILC2s) have emerged as pivotal regulators in the pathogenesis of diseases, with their roles in inflammation, metabolism, and tissue homeostasis becoming increasingly recognized. This review provides an overview of the current understanding of ILC2s in inflammation and metabolic disorders, including their functional contributions. Moreover, we will discuss how these cells adapt their metabolic processes to support their function and survival and how their metabolic requirements change under different physiological and pathological conditions. Lastly, we will review recent omics studies that have provided insights into the molecular and cellular characteristics of ILC2s. This includes transcriptomic, proteomic, and metabolomic analyses that have elucidated the gene expression profiles, protein interactions, and metabolic networks, respectively, associated with ILC2s. These studies have advanced our understanding of the functional diversity of ILC2s and their involvement in metabolic disease.

Additive effect of metabolic dysfunction-associated fatty liver disease on left ventricular function and global strain in type 2 diabetes mellitus patients: a 3.0 T CMR feature tracking study

Abstract Purpose Type 2 diabetes mellitus (T2DM) represents the most prevalent form of diabetes, exerting a significant influence on cardiovascular health. Concurrently, metabolic dysfunction-associated fatty liver disease (MAFLD) is closely linked to heightened cardiac dysfunction risk. Our study aimed to explore the additive effect of MAFLD on left ventricular (LV) deformation among T2DM patients, utilizing cardiac magnetic resonance (CMR) feature tracking technology. Methods This study retrospectively included 270 patients with T2DM, comprising 110 individuals with MAFLD and 160 without, alongside 80 age- and sex-matched healthy controls, all of whom underwent CMR examination. Parameters derived from CMR encompass those related to LV function and global strain metrics. LV global strain parameters include global radial peak strain (GRPS), longitudinal peak strain (GLPS), and circumferential peak strain (GCPS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR), measured across radial, circumferential, and longitudinal directions. Intergroup analysis, employing the Mann-Whitney U test, was utilized to compare LV function and global strain parameters. Results The LV function parameters, including LV end-diastolic volume (LVEDV), LVEDV index, LV end-systolic volume (LVESV), LVESVI, LV mass, and LV mass index, displayed a progressive augmentation from controls through T2DM patients without MAFLD, to those with MAFLD. In parallel, LVEF showed a declining trajectory across these groups. In contrast, LVSV and LVSVI were comparable among the three groups. In a similar vein, when examining global strain parameters derived from CMR, a significant and progressive deterioration is observed across the groups. GRPS, GCPS and GLPS, along with PSSR and PDSR in radial, circumferential, and longitudinal directions, manifest a pronounced decline moving from control subjects to T2DM patients without MAFLD, and further deteriorating in those with T2DM and MAFLD (All p-values < 0.05). To assess the effect of MAFLD severity on global peak strain, patients with T2DM and MAFLD were stratified into two groups: a mild MAFLD group (N=77) and a moderate to severe MAFLD group (N=33). Although there was a noticeable decline in GRPS, GCPS and GLPS, as well as in PSSR and PDSR across the three groups—from those without MAFLD to those with mild and then moderate to severe MAFLD—the observed differences did not reach statistical significance. The absence of statistical significance is likely due to the small sample sizes of the groups categorized by severity of MAFLD. Conclusions This study revealed that MAFLD has additive worsening effects on LV function and LV global strains in T2DM patients evaluated by CMR. Besides, moderate to severe MAFLD, compared to mild MAFLD, exhibits worse global strain parameters. Early detection and intervention of MAFLD might improve the prognosis of T2DM patients.

Serum Irisin, Myostatin, and Myonectin Correlate with Metabolic Health Markers, Liver Disease Progression, and Blood Pressure in Patients with Metabolic Dysfunction-Associated Fatty Liver Disease and Hypertension

Background/Objectives: Recent data indicate the involvement of skeletal muscles in the regulation of metabolism and in the pathogenesis of chronic noncommunicable diseases. The goal of our study was to describe the serum concentrations of myokines in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertension (HTN) and their correlation with laboratory parameters, blood pressure (BP), and MASLD severity. Methods: A total of 67 patients with MASLD and HTN underwent anthropometric measurements, laboratory tests, and point shear-wave elastography. The serum concentrations of myokines were measured using enzyme-linked immunosorbent assay (ELISA). Results: Patients with detectable serum myonectin concentrations had significantly higher maximum systolic blood pressure (p = 0.022) and higher blood levels of uric acid (p = 0.029). Serum irisin concentration ≥ 6.1 μg/mL was associated with higher FLI values (p = 0.042) and liver stiffness (p = 0.034), as well as with slightly higher waist circumference (p = 0.082) and triglyceride level (p = 0.062). Patients with serum myostatin concentration ≥ 4.98 ng/mL were significantly older (p = 0.033) and had a lower blood albumin level (p = 0.043). Conclusions: In conclusion, the myokine profile in patients with MASLD and HTN correlates both with the severity of MASLD and the parameters characteristic of metabolic health, suggesting the possible contribution of altered irisin, myonectin, and myostatin concentrations to the occurrence of cardiometabolic risks in patients with MASLD.

Circulating levels of amyloid-beta (1-40) peptide associate with cardiometabolic traits and risk for metabolic dysfunction-associated steatotic liver disease

Abstract Background and Aims The ageing-associated amyloid-beta 1-40 peptide (Αbeta40) has recently emerged as a blood-based biomarker of cardiovascular disease (CVD). Its levels predict future cardiovascular death and MACE in patients with established CVD. The clinical value of Abeta40 in patients with metabolic syndrome who do not concomitantly have clinically overt CVD or other end-organ damage remains poorly understood. At the present study we investigated the clinical value of plasma Αbeta40 in patients with pre- or established metabolic syndrome who are at risk for metabolic dysfunction-associated steatotic liver disease (MASLD). Methods Αbeta40 was measured in plasma by enzyme-linked immunosorbent assay and cardiometabolic traits were determined in a mixed population (n=888) of patients with established (n=243) and pre- or without metabolic syndrome (n=645) who did not have clinical signs of established cardiometabolic disease (heart failure, coronary artery disease, MASLD, chronic kidney disease). The endpoint of the study was the association of Abeta40 with cardiometabolic indices and risk (BARD score) for MASLD. Odds ratio (OR) was calculated by ordinal regression analysis for the increasing incidence of metabolic syndrome components per increasing Abeta40 (1-SD) after adjustment for age, sex, smoking status and hyperlipidemia. Results Abeta40 levels are associated with the presence of metabolic syndrome and with higher odds for increasing incidence of metabolic syndrome components after adjustment for sex, age, smoking status, hypertension and dyslipidemia. Increased Abeta40 plasma levels were associated with decreased HDL-C levels (OR: 1.004, 95% CI:1.000-1.009, P=0.049) and increased triglyceride levels (OR: 1.007, 95%CI: 1.001-1.012, P=0.033) after adjustment for traditional cardiovascular risk factors (age, sex, smoking status, hypertension and hyperlipidemia). Among the total population (n=888), we identified n=473 subjects with increased MASLD risk if any of the following was present: hepatic steatosis index≥36 or fatty liver index≥60 or Fib-4 index≥2.67 or NAFLD score≥0.675. Among patients with high-risk for MASLD, patients with increased BARD score had significantly higher Abeta40 levels (median Abeta40 concentration in patients with BARD score≥2 vs. patients with BARD score<2: 54.9 pg/ml (IQR=38.25) vs. 41.9 pg/m (IQR=30.35), P=0.012). Increased Abeta40 levels were associated with increased odds for AST/ALT≥0.8 ratio and increased odds for BARD score≥2 after adjustment for age, sex, smoking status, hypertension and hyperlipidemia. Conclusion Our findings suggest that Abeta40 peptide is associated with cardiometabolic traits and risk for MASLD. Whether Abeta40 may emerge as an early cardiometabolic prognostic biomarker, future longitudinal studies are warranted to determine the prognostic value of Abeta40 for the development of cardiometabolic diseases in patients with metabolic syndrome.

Novel insights of phenylalanine in Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) and cardiovascular complications

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to cardiovascular risk, necessitating an exploration of potential metabolic contributors, such as amino acids. While amino acids are implicated in metabolic disorders, their specific relationship with MASLD and subsequent cardiovascular complications is not well-defined. We aimed to delineate the association between circulating amino acids and MASLD, identifying amino acids that could potentially link MASLD to cardiovascular issues. Methods Utilizing UK Biobank data, we tested the association of ten amino acids with MASLD in a cohort of 72,626 MASLD cases and 128,102 controls. Afterwards, we performed Mendelian Randomization (MR) using genome-wide association study (GWAS) data from 8,434 MASLD cases and 770,180 controls, and GWAS of amino acids including 115,052 participants from UK Biobank. Multiple MR methods, including MR-Egger, Cochran's Q-test, and MR-PRESSO, were applied to assess pleiotropy and heterogeneity. Survival analysis in MASLD patients assessed the link between significant amino acid and incident severe cardiovascular outcomes, including stroke, heart failure, myocardial infarction, and mortality, using three different covariate combinations: Model 1 included age, sex, and fasting time; Model 2 included in addition smoking, alcohol use, education, physical activity, and Model 3 included body mass index (BMI) in addition to model 2. Results Nine out of the ten amino acids were statistically significantly associated with MASLD across all three models (p<6.25×10^-3). Among them valine, leucine, isoleucine, total branched-chain amino acids, tyrosine, alanine, and phenylalanine were positively associated with MASLD, while glutamine and glycine were negatively associated with MASLD. The genetic predisposition of MASLD was significantly associated with increased phenylalanine (beta=0.05, p=4.0×10^-4) and tyrosine (beta=0.15, p=2.0×10^-3), suggesting that alterations in these amino acids may result from the progression of MASLD. We also detected heterogeneity (Cochran’s Q-test: p=8.4×10^-9) and pleiotropy (MR-Egger: p=0.02) for tyrosine, but not for phenylalanine. Furthermore, phenylalanine levels in MASLD patients were significantly (p<6.25×10^-3) associated with the incidence of heart failure, stroke, and mortality, but not with myocardial infarction across all three models. We did not identify a significant association between baseline tyrosine levels and any cardiovascular complications or mortality across the three models (Figure 1). Conclusion Our findings indicate a strong association between certain amino acids and MASLD, with phenylalanine, in particular, emerging as a potential mediator of cardiovascular risk in MASLD patients. The absence of heterogeneity and pleiotropy for phenylalanine strengthens its candidacy as a biomarker for future cardiovascular complications in MASLD.

An examination of co-existence of metabolic dysfunction-associated liver disease and chronic kidney disease and its effect on long-term mortality in patients with acute myocardial infarction

Abstract Background Metabolic dysfunction-associated liver disease (MASLD) and chronic kidney disease (CKD) are both diseases that can cause increased cardiovascular risk. Recent studies have revealed that the combination of both is a more potent risk factor for ischemic heart disease. However, the mortality and outcomes of patients presenting with acute myocardial infarction (AMI) with varying combination of these two risk factors have yet to be examined. Aims Our research aims to examine the effects of concomitant MASLD and CKD on mortality in patients presenting with AMI. Methods This research examined the features and outcomes of individuals experiencing AMI at our institution. The patients were stratified into 4 groups – patients without MASLD or CKD (MASLD(-)/CKD(-)), patients with MASLD without CKD (MASLD(+)/CKD (-)), patients with CKD without MASLD (MASLD(-)/CKD(+)), and patients with both MASLD and CKD (MASLD(+)/CKD(+)). MASLD was identified as hepatic steatosis along with at least one of five metabolic criteria, and hepatic steatosis was assessed using the Hepatic Steatosis Index. CKD is defined as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m². A Kaplan-Meier curve was generated to analyse long-term all-cause mortality, and Cox regression analysis was used to identify independent predictors of mortality. Results A total of 6757 patients who presented with AMI were examined over 3.2 ± 2.4 years. Of whom, 3766 (55.7%) individuals were in the MASLD(-)/CKD(-) group, 1945 (28.8%) in the MASLD(+)/CKD (-) group, 675 (10.0%) in the MASLD(-)/CKD(+) group and 371 (5.5%) in the MASLD(+)/CKD(+) group. The MASLD(+)/CKD(+) group had the highest risk of cardiogenic shock compared to their counterparts (p<0.001). The highest 30-day mortality rates were found in the MASLD(+)/CKD(+) group (17.8%), followed by MASLD(-)/CKD(+) (11.6%), MASLD(+)/CKD(-) (4.6%) and MASLD(-)/CKD(-) (4.0%) (p<0.001). In terms of long-term mortality, the Kaplan-Meier curve demonstrated that both MASLD(-)/CKD(+) and MASLD(+)/CKD(+) groups had unfavorable survival following an AMI. Conclusions Patients with AMI, in the presence of concomitant MASLD and CKD, had the highest 30-day mortality rates. They were at the highest risks of AMI-related complications such as heart failure and cardiogenic shock. This study highlights the prognostic impact of cardiovascular-liver-kidney-metabolic health on AMI, and future studies are warranted to mitigate this risk.Figure 1:30 – day all cause mortalityFigure 2:Long term mortality

Metabolomic fingerprinting of milk fever cows: Pre- and postpartum metabolite alterations.

Milk fever (MF), a metabolic disorder in dairy cows characterized by low blood calcium concentrations postpartum, is well-recognized clinically. However, comprehensive data on the alteration of metabolites associated with this condition remains sparse. Delineate serum metabolite profiles and metabolic pathways preceding, coinciding with, and after the onset of MF. Twenty-six cows, including 20 healthy cows and 6 cows initially affected by MF. Because of culling, the number of MF-affected cows decreased to 4 at MF week, +4 weeks, and +8 weeks postpartum. A nested case-control longitudinal study was conducted, with blood samples collected at -8 and -4 weeks prepartum, MF week, and +4 and +8 weeks postpartum. Serum analysis utilized direct injection/liquid chromatography/tandem mass spectrometry (DI/LC/MS/MS) techniques. Key findings included the identification of diverse metabolites such as hexose, amino acids, phosphatidylcholines, lysophosphatidylcholines, and sphingomyelin, which varied between studied groups (P < .05). The most marked metabolic alterations were observed 4 weeks prepartum. In total, 42, 56, 38, 29, and 24 metabolites distinguished the MF group at the respective time points (P < .05). Additionally, 33 metabolic pathways, including amino acid, antioxidant metabolism, fatty acid degradation, and carbohydrate processing, were impacted (P < .05). Metabolic disruptions in dairy cows begin several weeks before the clinical manifestation of MF and persist up to 8 weeks postpartum. These findings emphasize the complexity of MF, extending beyond only hypocalcemia and indicate the necessity for preemptive monitoring in dairy herd management.

Histological Change of Placenta in Diabetic Pregnant Women in Comparison to Normal Pregnant Women

Background: The placenta is a foeto-maternal organ and its alterations is directly related to the disease’s length and severity. The human placenta experiences a number of functional and structural pathologic alterations when complicated by metabolic disorder such as diabetes mellitus. Methods: This cross-sectional comparative study was conducted over a period of threeyears from January 2019 to December 2021 at the Department of Anatomy, Rajshahi Medical College, Rajshahi, in collaboration with the Department of Obstetrics and Gynaecology, Rajshahi Medical College Hospital and Diabetic Hospital Rajshahi, Bangladesh. The study was carried out on 70 pregnant women, among them 35 diabetics and 35 non-diabetics. The fibrinoid necrosis, syncytial knot and immature villi of the placenta were studied in diabetic and non-diabetic pregnant women. SPSS software, version-24 was used for data analysis, with a p-value &lt; 0.05 indicating statistically significance for all tests. Results: The diabetic and non-diabetic pregnant women groups were almost identical in terms of attachment of umbilical cord to placenta with marginal attachment being more often found in either group (p = 0.829). Histological examination of placenta showed that fibrinoid necrosis was common in placenta of diabetic mothers than that of the normal mothers (p &lt; 0.001). Syncytial knot and immature villi were higher in the former group than those in the latter group, here p values were also less than .001. Conclusion: Histological findings (fibrinoid necrosis, syncytial knot and immature villi) were more in placenta of diabetic mother and they were highly significant different between the groups. EWMCJ Vol. 12, No. 1&amp;2, January-July 2024: 27-33