Metabolic Disorders Research Articles

Therapeutic Potential of FTO Demethylase in Metabolism and Disease Pathways.

The crucial involvement of the Fat Mass and Obesity-associated (FTO) protein in both metabolic and non-metabolic diseases has been documented since its discovery. This enzyme, known as FTO, is a demethylase that belongs to the 2-oxoglutarate-dependent nucleic acid demethylases. Its primary function is to target N6-methyladenosine (m6A) in RNA, which is crucial in regulating RNA stability, processing, and expression. This review facilitates understanding the FTO gene variations linked to Body Mass Index (BMI) and obesity, resulting in increased vulnerability to type 2 diabetes. While prior reviews have already discussed the link between FTO and BMI and its impact on type 2 diabetes, the current review additionally examines the emerging evidence suggesting a direct influence of the FTO gene on metabolism. Additionally, the paper discusses the alternative role of FTO and emphasizes the endophenotypes in neurological circuits and the demethylase function of FTO in neurodegenerative disorders. The review further examines the impact of FTO on several physiological systems and emphasizes the need to study FTO as a potential multitarget for future research and therapies.

Impact of obesity, genetic predisposition and comorbidities on pregnancy-related hypertension

Purpose: This study aims to explore the impact of obesity, genetic predisposition, and comorbidities on pregnancy-related hypertension. Given the rising prevalence of maternal obesity and associated metabolic disorders, understanding how these factors contribute to hypertensive complications during pregnancy is crucial for developing effective prevention and management strategies. The study also examines the role of genetic susceptibility and pre-existing medical conditions in exacerbating hypertensive risks, emphasizing the need for a holistic approach in maternal healthcare. Research Design and Methodology: This study employs a systematic literature review (SLR) to synthesize findings from existing research on the relationship between obesity, genetic factors, and comorbidities with pregnancy-related hypertension. Relevant peer-reviewed articles from Elsevier, Emerald, Wiley, and Springer published after 2018 were analyzed to identify key trends, mechanisms, and clinical implications. The review integrates evidence from obstetrics, endocrinology, genetics, and public health to understand the topic comprehensively. Findings and Discussion: The study reveals that obesity significantly contributes to hypertensive disorders in pregnancy through mechanisms such as endothelial dysfunction, chronic inflammation, insulin resistance, and RAAS activation. Genetic predisposition, particularly polymorphisms in RAAS-related genes (AGT, ACE, AGTR1) and endothelial function genes (eNOS, VEGF), is strongly associated with increased hypertension risk. Additionally, pre-existing conditions such as diabetes mellitus, chronic hypertension, kidney disease, and autoimmune disorders further aggravate hypertensive complications. Implications: The findings emphasize the necessity for early screening programs, personalized treatment approaches, and interdisciplinary prenatal care. Healthcare policymakers should develop standardized guidelines for managing hypertensive pregnancies complicated by obesity and comorbidities. The study highlights the importance of lifestyle interventions, genetic screening, and pharmacological advancements in reducing pregnancy-related hypertension risks and improving maternal-fetal health outcomes.

LIMA1 O-GlcNAcylation Promotes Hepatic Lipid Deposition through Inducing β-catenin-Regulated FASn Expression in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Hepatic lipid deposition is a key factor in progressing metabolic dysfunction-associated steatotic liver disease (MASLD). This study investigates the impact of the LIM domain and actin-binding protein 1 (LIMA1) on hepatic steatotic in MASLD and explore the underlying mechanisms. Increased levels of LIMA1 is observed in both serum and serum sEV of metabolic dysfunction-associated steatohepatitis (MASH) patients compared to healthy controls, with AUROC values of 0.76 and 0.86, respectively. Furthermore, increased LIMA1 O-GlcNAcylation is observed in mouse models of MASLD, and steatotic hepatocytes. Mechanistic studies revealed that steatosis upregulated Host cell factor 1 (HCF1) and O-GlcNAc transferase (OGT) expression, leading to catalyzed O-GlcNAcylation at the T662 site of LIMA1 and subsequent inhibition of its ubiquitin-dependent degradation. O-GlcNAcylation of LIMA1 enhances hepatocyte lipid deposition by activating β-catenin/FASn-associated signaling. Additionally, compared with their AAV8-TBG-LIMA1-WT counterparts, AAV8-TBG-LIMA1ΔT662 injection exhibited decreases in systemic insulin resistance, steatosis severity, inflammation and fibrosis in HFD-fed and CDAHFD-fed LIMA1 HKO (hepatocyte-specific knockout) mice. Moreover, LTH-sEV-mediated delivery of LIMA1 promoted MASLD progression by promoting hepatic stellate cell (HSC) activation. The findings suggest that serum sEV LIMA1 may be a potential noninvasive biomarker and therapeutic target for individuals with MASH.

Mechanisms and Therapeutic Potential of Key Anti-inflammatory Metabiotics: Trans-Vaccenic Acid, Indole-3-Lactic Acid, Thiamine, and Butyric Acid.

Identifying metabolites produced by probiotic bacteria, also known as metabiotics, is becoming increasingly common due to their anti-inflammatory, anti-obesogenic, and immunomodulatory effects. Postbiotics alongside diet, regulate both physical and mental health, as the microbiota members can interact physically with host cells or through secretion of nutrients and metabiotics. These metabiotics also reduce the severity of certain metabolic disorders and support the proper functioning of various organs and systems. In this review, we describe the mechanisms of action of trans-vaccenic acid (TVA), indole-3-lactic acid (ILA), thiamine (vitamin B1), and butyric acid metabolites produced or induced by probiotics such as Lactobacillus and/or Bifidobacterium, among others and previously identified using analytical techniques such as mass spectrometry (LC-MS). Within their mechanisms of action, Trans-vaccenic acid exerts anti-inflammatory effects and helps alleviate complications associated with metabolic diseases. Indole metabolites promote IL-22 production and regulate epithelial cell proliferation and antimicrobial peptide production. Thiamin is essential for energy metabolism regulation, and butyric acid regulates the brain-gut axis and also regulates immune response. This review expands our understanding of the potential therapeutic useofmetabiotics.

Impaired cognitive function and decreased monoamine neurotransmitters in the DNAJC12 gene knockout mouse model

BackgroundHyperphenylalaninemia, a prevalent amino acid metabolism disorder, often results in cognitive impairment. Recent studies have identified a rare variant of this disorder caused by mutations in the DNAJC12 gene. The specific mechanisms by which DNAJC12 mutations lead to hyperphenylalaninemia and the lack of an animal model for study remain significant gaps in understanding.PurposeThis study aims to elucidate the role of DNAJC12 in intellectual disability and explore the mechanisms by which DNAJC12 deficiency leads to hyperphenylalaninemia through developing a DNAJC12 gene knockout mouse model.MethodsWe thoroughly examined the clinical features and genetic mutations evident in two patients with biallelic mutations in the DNAJC12 gene. Based on the patient’s mutation locations, we determined the target site for the knockout utilizing CRISPR/Cas9 technology. To assess the impact of these mutations on DNAJC12 expression, we used quantitative real-time PCR and Western blotting techniques to measure mRNA and protein levels, respectively. The Morris water maze test was administered to evaluate the cognitive functions of the mice. Additionally, we utilized High-Performance Liquid Chromatography (HPLC) to measure serum aromatic amino acids and brain monoamines, facilitating an investigation into the metabolism of phenylalanine and tyrosine.ResultsWe reported two patients with mutations in the DNAJC12 gene. Case 1 carried the mutations c.158-1G > A and c.262 C > T in the DNAJC12 gene. He presented with nocturnal eye closure, crying, and arching back in reverse tension before treatment, suggesting a neurotransmitter metabolism disorder. Case 2 carried the mutations c.473 C > G, and c.102 deletion in the DNAJC12 gene. He showed elevated blood phenylalanine levels, although further clinical details were not available. Based on the patients’ mutation locations, exons 2–4 of the DNAJC12 gene were targeted and eliminated. In our animal model experiments, DNAJC12 gene knockout mice exhibited a complete absence of DNAJC12 expression at both mRNA and protein levels. These knockout mice showed significant deficits in learning and memory performance as assessed by the Morris water maze test. Quantitative real-time PCR analysis indicated no significant differences in the levels of aromatic amino hydroxylases between knockout and wild-type mice. However, Western blot analysis revealed a substantial reduction in phenylalanine hydroxylase (PAH) protein levels in the liver of knockout mice, while tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2) expression remained unchanged. HPLC analysis demonstrated increased serum Phe concentrations and decreased levels of brain neurotransmitters in the knockout group.ConclusionsWe report two patients with four novel DNAJC12 mutations (c.158-1G > A, c.262 C > T, c.473 C > G, c.102delT), expanding the mutation spectrum. Based on the patients’ mutation location, we established the first DNAJC12 gene knockout mouse model. The knockout mice exhibit hyperphenylalaninemia, impaired cognitive function, and decreased monoamine neurotransmitters. DNAJC12 deficiency may contribute to the clinical phenotype via the PAH pathway, potentially at the post-transcriptional level.

Movement Disorders after Dengue Virus Infection: A Scoping Review.

Movement disorders after dengue virus (DENV) infection have been increasingly recognized. We aimed to synthesize the clinical and paraclinical characteristics, treatment responses, and outcomes of these neurologic complications. We systematically reviewed PubMed, Embase, Scopus, and LILACS databases up to September 2023 following a published protocol. We identified 73 cases of DENV-induced movement disorders. Cerebellar ataxia was the most common, followed by parkinsonism, opsoclonus-myoclonus-ataxia syndrome, and dystonia. Movement disorders typically developed within 14 days of DENV infection and were associated with a range of neurological symptoms, including cognitive impairment and psychiatric disturbances. Neuroimaging studies frequently showed abnormalities in the basal ganglia and brainstem. Treatment varied depending on the specific movement disorder and included corticosteroids, intravenous immunoglobulin, and symptomatic medications. Whereas a handful of cases met the criteria for acute encephalitis, many lacked sufficient data to establish a definitive diagnosis. Para-infectious and postinfectious immune-mediated movement disorders were also reported. A rare case of chronic progressive panencephalitis due to DENV infection highlights the potential for long-term neurological consequences. Other DENV-related complications, such as stroke, pituitary apoplexy, subacute thyroiditis, and metabolic disturbances, can also cause movement disorders. We emphasize the importance of recognizing the diverse neurological manifestations of DENV infection and the need for further research to improve our understanding of the underlying mechanisms and optimize treatment strategies. We propose a more rigorous approach to determining the causality between infection and movement disorder, demanding stronger evidence beyond mere association and advocating for targeted research to fill the existing knowledge gaps. © 2025 International Parkinson and Movement Disorder Society.

Genetic evidence for the liver-brain axis: lipid metabolism and neurodegenerative disease risk

BackgroundThe liver‒brain axis is critical in neurodegenerative diseases (NDs), with lipid metabolism influencing neuroinflammation and microglial function. A systematic investigation of the genetic relationship between lipid metabolism abnormalities and ND, namely, Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), is lacking. To assess potential causal links between ND and six lipid parameters, two-sample Mendelian randomization (MR) was used.MethodsLarge-scale European ancestry GWAS data for lipid parameters and ND (AD, ALS, PD, and MS) were used. Genetic variants demonstrating significant correlations (P < 5 × 10−8) with lipid metabolism parameters were identified and employed as instrumental variables (IVs) after proper validation. The research incorporated UK Biobank genomic data to examine associations between genetic variants and lipid metabolism parameters. The analysis included primary MR, sensitivity analyses, and multivariable MR, which considered potential mediators.ResultsMR via the inverse-variance weighted method revealed causal effects of cholesterol (CHOL, OR = 1.10, 95% CI: 1.03–1.18, P = 4.23 × 10⁻3) and low-density lipoprotein cholesterol (LDLC, OR = 1.10, 95% CI: 1.03–1.17, P = 3.28 × 10⁻3) on the risk of ALS, which were validated across multiple methods. Potential correlations were observed between ApoB and ALS and inversely correlated with AD, whereas no significant associations were found for PD or MS. CHOL and LDLC associations with ALS demonstrated no significant heterogeneity or pleiotropy, supporting their reliability.ConclusionsHigher CHOL and LDLC levels were associated with increased ALS risk, suggesting a potential causal link, and supporting the liver‒brain axis hypothesis in ND. Current genetic evidence does not support a significant role for lipid metabolism in PD and MS etiology, suggesting the relationship between lipid metabolism and other NDs may be more complex and warrants further investigation.

Effect of rhGH treatment on lipidome and brown fat activity in prepuberal small for gestational age children: a pilot study

Recombinant human growth hormone (rhGH) therapy is the primary treatment for children born small for gestational age (SGA) who fail to show spontaneous catch-up growth by two or four years. While its effects on white adipose tissue are well-documented, this pilot study aimed to investigate its impact on the lipidome and the thermogenic and endocrine activities of brown adipose tissue (BAT) in SGA children following rhGH treatment. The study involved 11 SGA children divided into two groups: (a) SGA children who were not treated with rhGH (n = 4) and (b) SGA children who received rhGH treatment with Saizen® (n = 7). This second group of seven SGA children was followed for 12 months after initiating rhGH treatment. Interventions included 12-hour fasting blood extraction and infrared thermography at baseline and 3 and 12 months post-treatment. Five appropriate-for-gestational-age (AGA) children served as controls. Exclusion criteria included endocrinological, genetic, or chronic diseases. Untargeted lipidomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS), and serum biomarker levels were measured using ELISA assays. Serum lipidomic analysis revealed that free fatty acids (FFAs) increased to levels close to those of the AGA group after three months of rhGH administration, including polyunsaturated fatty acids, correlating with reduced leptin levels. Elevated levels of 1a,1b-dihomo-PGJ2 and adrenic acid suggested potential aging markers. rhGH treatment also significantly reduced meteorin-like (METRNL) and monocyte chemoattractant protein-1 (MCP1) serum levels to control levels. rhGH influences the serum lipidome, promoting changes in maturation and metabolism. Further research is required to clarify the direct effects of rhGH on specific lipid species and batokines, potentially addressing metabolic disturbances linked to obesity and aging.

Early-life gut mycobiome core species modulate metabolic health in mice

The gut microbiome causally contributes to obesity; however, the role of fungi remains understudied. We previously identified three core species of the infant gut mycobiome (Rhodotorula mucilaginosa, Malassezia restricta and Candida albicans) that correlated with body mass index, however their causal contributions to obesity development are unknown. Here we show the effects of early-life colonization by these fungal species on metabolic health in gnotobiotic mice fed standard (SD) or high-fat-high-sucrose (HFHS) diets. Each species resulted in bacterial microbiome compositional and functional differences. R. mucilaginosa and M. restricta increased adiposity in mice fed SD, while only R. mucilaginosa exacerbated metabolic disease. In contrast, C. albicans resulted in leanness and resistance to diet-induced obesity. Intestinal nutrient transporter expression was unaffected by the presence of fungi in jejunal enteroids, yet the immune landscape in white adipose tissue was distinctly impacted by each fungal species, suggesting that these phenotypes may be a result of fungal immune regulation. This work revealed that three common fungal colonizers have distinct causal influences on obesity and metabolic inflammation and justifies the consideration of fungi in microbiome research on host metabolism.

Development of cyclopeptide inhibitors specifically disrupting FXR-coactivator interaction in the intestine as a novel therapeutic strategy for MASH

Abstract Intestinal farnesoid X receptor (FXR) antagonists have been proven to be efficacious in ameliorating metabolic diseases, particularly for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). All the reported FXR antagonists target to the ligand-binding pocket (LBP) of the receptor, whereas antagonist acting on the non-LBP site of nuclear receptor (NR) is conceived as a promising strategy to discover novel FXR antagonist. Here, we have postulated the hypothesis of antagonizing FXR by disrupting the interaction between FXR and coactivators, and have successfully developed a series of macrocyclic peptides as FXR antagonists based on this premise. The cyclopeptide DC646 not only exhibits potent inhibitory activity of FXR, but also demonstrates a high degree of selectivity towards other NRs. Moreover, cyclopeptide DC646 has high potential therapeutic benefit for the treatment of MASH in an intestinal FXR-dependent manner, along with a commendable safety profile. Mechanistically, distinct from other known FXR antagonists, cyclopeptide DC646 specifically binds to the coactivator binding site of FXR, which can block the coactivator recruitment, reducing the circulation of intestine-derived ceramides to the liver, and promoting the release of glucagon-like peptide-1 (GLP-1). Overall, we identify a novel cyclopeptide that targets FXR-coactivator interaction, paving the way for a new approach to treating MASH with FXR antagonists.

The association between visceral fat metabolic score and stroke: mediation by declining kidney function

BackgroundStroke is a leading cause of mortality and disability worldwide. Metabolic Score for Visceral Fat (METS-VF), a metric of visceral obesity, has emerged as a novel predictor of metabolic diseases. However, its association with stroke remains unclear. This study investigates the relationship between METS-VF and the risk of stroke, as well as the potential mediating role of kidney function.MethodsData from the 1999–2020 National Health and Nutrition Examination Survey (NHANES) were analyzed, including 19,109 participants. Weighted logistic regression models were used to assess the association between METS-VF and stroke risk, with restricted cubic splines employed to explore their non-linear relationships. Mediation analysis examined the role of kidney function, measured by estimated glomerular filtration rate (eGFR). Subgroup and sensitivity analyses, including propensity score matching (PSM) and multiple imputations, were conducted to ensure the robustness of the findings.ResultsHigher METS-VF was significantly associated with an increased risk of stroke (OR = 2.78, 95% CI: 1.71–4.52, P < 0.001) after adjusting for multiple covariates. A non-linear relationship was observed, with stroke risk sharply increasing when METS-VF exceeded 7.00. Mediation analysis revealed that declining eGFR mediated 26.72% of the METS-VF-stroke association. Subgroup analysis indicated that the association was stronger in men (OR = 5.06, 95% CI: 2.80–9.12, P < 0.001) than in women (OR = 2.01, 95% CI: 1.03–3.92, P = 0.04, P for interaction = 0.01). Sensitivity analyses using PSM and multiple imputations confirmed the robustness of the results.ConclusionsMETS-VF is independently associated with stroke risk, showing a non-linear relationship, with a potential mediating role of declining kidney function.

Impact of shear wave elastography and attenuation imaging for predicting life-threatening event in patients with metabolic dysfunction-associated steatotic liver disease

We aimed to elucidate the value of ultrasound-based biomarkers for predicting the major life-threatening events in metabolic dysfunction-associated steatotic liver disease (MASLD). We established a prospective cohort of 279 patients who underwent two-dimensional shear wave elastography (2D-SWE), ultrasound-guided attenuation parameter (UGAP). An area under the curve analysis was performed to determine the cutoff values of liver stiffness measurements (LSM) by 2D-SWE and attenuation coefficient (AC) by UGAP for a moderate fibrosis and a moderate steatosis. We then classified the cohort into Groups A (low LSM and low AC), B (low LSM and high AC), C (high LSM and high AC), and D (high LSM and low AC). We compared the incidence of events between the groups, and estimated the hazard ratios (HRs) with 95% confidence intervals (CIs). The LSM and AC cut off values were 8.37 kPa and 0.62 dB/cm/MHz, respectively. The cumulative incidence rate in Groups A, B, C, and D were 11.2%, 12.2%, 29.5%, and 31.0%/5years, respectively (p < 0.05). LSM (HRs = 1.20, 95%CIs: 1.09–1.32, p < 0.01), and AC (HRs = 1.62, 95%CIs: 1.04–2.51, p = 0.03) were associated with life-threatening events. A combination of 2D-SWE and UGAP may help identify patients with MASLD at high risk for subsequent life-threatening events.

Harnessing the fundamental roles of vitamins: the potent anti-oxidants in longevity.

Aging is a complex and heterogeneous biological process characterized by telomere attrition, genomic instability, mitochondrial dysfunction, and disruption in nutrient sensing. Besides contributing to the progression of cancer, metabolic disorders, and neurodegenerative diseases, these manifestations of aging also adversely affect organ function. It is crucial to understand these mechanisms and identify interventions to modulate them to promote healthy aging and prevent age-related diseases. Vitamins have emerged as potential modulators of aging beyond their traditional roles in health maintenance. There is an increasing body of evidence that hormetic effects of vitamins are responsible for activating cellular stress responses, repair mechanisms, and homeostatic processes when mild stress is induced by certain vitamins. It is evident from this dual role that vitamins play a significant role in preventing frailty, promoting resilience, and mitigating age-related cellular damage. Moreover, addressing vitamin deficiencies in the elderly could have a significant impact on slowing aging and extending life expectancy. A review of recent advances in the role of vitamins in delaying aging processes and promoting multiorgan health is presented in this article. The purpose of this paper is to provide a comprehensive framework for using vitamins as strategic tools for fostering longevity and vitality. It offers a fresh perspective on vitamins' role in aging research by bridging biological mechanisms and clinical opportunities.

Negative emotional states and metabolic disorders in arterial hypertension in coal industry workers

Negative emotional states and metabolic disorders in arterial hypertension in coal industry workers

Unlocking the secrets of the human gut microbiota: Comprehensive review on its role in different diseases

The human gut microbiota, a complex and diverse community of microorganisms, plays a crucial role in maintaining overall health by influencing various physiological processes, including digestion, immune function, and disease susceptibility. The balance between beneficial and harmful bacteria is essential for health, with dysbiosis - disruption of this balance - linked to numerous conditions such as metabolic disorders, autoimmune diseases, and cancers. This review highlights key genera such as Enterococcus , Ruminococcus , Bacteroides , Bifidobacterium , Escherichia coli , Akkermansia muciniphila , Firmicutes (including Clostridium and Lactobacillus ), and Roseburia due to their well-established roles in immune regulation and metabolic processes, but other bacteria, including Clostridioides difficile , Salmonella , Helicobacter pylori , and Fusobacterium nucleatum , are also implicated in dysbiosis and various diseases. Pathogenic bacteria, including Escherichia coli and Bacteroides fragilis , contribute to inflammation and cancer progression by disrupting immune responses and damaging tissues. The potential for microbiota-based therapies, such as probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, to improve health outcomes is examined. Future research directions in the integration of multi-omics, the impact of diet and lifestyle on microbiota composition, and advancing microbiota engineering techniques are also discussed. Understanding the gut microbiota’s role in health and disease is essential for formulating personalized, efficacious treatments and preventive strategies, thereby enhancing health outcomes and progressing microbiome research.

Metabolic Messengers: small extracellular vesicles.

Small extracellular vesicles (sEVs) are signalling molecules and biomarkers of cell status that govern a complex intraorgan and interorgan communication system through their cargo. Initially recognized as a waste disposal mechanism, they have emerged as important metabolic regulators. They transfer biological signals to recipient cells through their cargo content, and microRNAs (miRNAs) often mediate their metabolic effects. This review provides a concise overview of sEVs, specifically in the context of obesity-associated chronic inflammation and related metabolic disorders, describing their role as metabolic messengers, identifying their key sites of action and elucidating their mechanisms. We highlight studies that have shaped our understanding of sEV metabolism, address critical questions for future exploration, discuss the use of miRNAs as disease biomarkers and provide insights into the therapeutic potential of sEVs or specific miRNAs for treating metabolic diseases and related disorders in the future.

Incidence and risk factors of ocular complications among patients with homocystinuria in Saudi Arabia: a cross-sectional study

Background: Cysteine beta-synthase deficiency, often known as classic homocystinuria, is an uncommon inborn mistake in methionine metabolism. Developmental delay, intellectual incapacity, skeletal and vascular symptoms, and ocular abnormalities are possible main clinical characteristics. Objective: This study sought to describe the ocular anomalies that King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia, homocystinuria patients presented with between 2018 and 2022. Methods: This retrospective research included 6 homocystinuria patients. Demographic and clinical characteristics of patients as age, gender, comorbidities were collected. Relevant clinical and ophthalmic assessments, like visual acuity, fundus examination findings, complications and type of surgery were also reported. Results: Six patients with homocystinuria (12 eyes) were included. Associated diseases were mostly mental retardation (100%), epilepsy (66.7%), developmental delay (50.0%), scoliosis (33.3%), bronchiectasis (16.7%), thrombophilia (16.7%), metabolic disorders (16.7%) and deep venous thrombosis (16.7%). All patients had ectopia lentis (100%), while one patient (16.7%) had eye ectropion, one patient (16.7%) had anterior uveitis and one patient (16.7%) had scleromalacia. Surgery type was mostly Lensectomy and vitrectomy (83.3%) then scleral fixation (16.7%), and Grice green procedure (16.7%). There were insignificant differences between first and last Autoref readings in spherical, cylinder and axis errors of right and left eyes Conclusions: Late-diagnosed homocystinuria patients frequently have abnormalities of the eyes. Ectopia lentis should always raise the possibility that homocystinuria is the cause of the condition.

Molecular Dissection of the Role of ACE2 in Glucose Homeostasis.

Angiotensin Converting Enzyme 2 (ACE2) was discovered 25 years ago as a negative regulator of renin-angiotensin system, opposing the effects of angiotensin-II. Beyond its well-demonstrated roles in cardiovascular regulation and Covid-19 pathology, ACE2 is involved in a plethora of physio-pathological processes. In this review, we summarize the latest discoveries on the role of ACE2 in glucose homeostasis and regulation of metabolism. In the endocrine pancreas, ACE2 is expressed at low levels in β cells, but loss of its expression inhibits glucose-stimulated insulin secretion and impairs glucose tolerance. Conversely, overexpression of ACE2 improved glycemia and suggests that recombinant ACE2 might be a future therapy for diabetes. In the skeletal muscle of ACE2-deficient mice, a progressive triglyceride accumulation was observed, whereas in diabetic kidney the initial increase in ACE2 is followed by a chronic reduction of expression in kidney tubules and impairment of glucose metabolism. At the intestinal level, dysregulation of the enzyme alters the amino acid absorption and intestinal microbiome, while at the hepatic level, ACE2 protects against diabetic fatty liver disease. Not least, ACE2 is upregulated in adipocytes in response to nutritional stimuli and administration of recombinant ACE2 decreased body weight and increased thermogenesis. In addition to tissue-specific regulation of ACE2 function, the enzyme undergoes complex cellular posttranslational modifications which are changed during diabetes evolution, with at least proteolytic cleavage and ubiquitination leading to modifications in ACE2 activity. Detailed characterization of ACE2 in specific cellular- and tissue-manner holds promise for improving therapeutic outcomes in diabetes and metabolic disorders.

Dietary and lifestyle patterns identified through reduced rank regression and their association with insulin-related disorders: a prospective analysis from the Tehran Lipid and Glucose Study

BackgroundSince foods are consumed in combinations that also interact with other lifestyle variables such as body mass index(BMI) and physical activity, it is difficult to separate the role of single foods or a lifestyle variable alone in predicting the risk of chronic diseases such as metabolic disorders. Therefore, a suitable way to examine the combined effect of food consumption and its interaction with other lifestyle variables is to derive dietary patterns and lifestyle patterns using appropriate statistical methods. This study aimed to derive two dietary and lifestyle patterns related to hyperinsulinemia and insulin resistance(IR) using reduced rank regression(RRR) analysis.MethodsThe current study was conducted on 1063 individuals aged ≥ 25 years old of the Tehran Lipid and Glucose Study who have complete data on fasting blood sugar, plasma insulin, anthropometric variables, and nutritional intakes. Dietary intakes were collected using a food frequency questionnaire. Dietary and lifestyle patterns were identified via RRR analysis, using 34 food groups, BMI, smoking, and physical activity as predictor variables, and fasting serum insulin and HOMA-IR as response biomarkers.ResultsRRR derived a dietary pattern with a higher intake of processed meat, doogh, pickles, lemon juices, fish, and a lower intake of starchy vegetables, garlic and onion, dried fruits, nuts, red meat, dairy products, and coffee as predictive variables for IR and hyperinsulinemia. Also, RRR derived a lifestyle pattern based on the above-mentioned dietary pattern and high BMI as response variables. In the final adjusted model of cross-sectional analysis, the odds of hyperinsulinemia(OR:1.23,95%CI:1.08–1.41,Ptrend=0.002) and IR(OR:1.52,95%CI:1.25–1.86,Ptrend<0.001) were elevated with increasing each quartile of RRR-derived dietary pattern score. Also, a higher adherence to RRR-derived lifestyle pattern was associated with higher odds of hyperinsulinemia(OR:2.49,95%CI:2.14–2.88,Ptrend<0.001) and IR(OR:3.20,95%CI:2.50–4.10,Ptrend<0.001). Moreover, after three years of follow-up, the risk of hyperinsulinemia(OR:1.30,95%CI:1.08–1.56,Ptrend=0.006) and IR(OR:1.26,95%CI:1.01–1.58,Ptrend=0.037) incidence were increased per each quartile increase of the RRR-derived lifestyle pattern.ConclusionsOur findings suggested that a dietary pattern and lifestyle with elevated BMI level, higher consumption of processed meat, doogh, pickles, lemon juices, and fish, and lower consumption of starchy vegetables, garlic and onion, dried fruits, nuts, red meat, dairy products, coffee may be associated with a higher risk of hyperinsulinemia and IR. It is suggested that further studies with a larger sample size and more extended follow-up duration, especially in other populations with different lifestyles and food habits be performed to confirm the findings of the current study.

Dietary and plasma atherogenic and thrombogenic indices and cardiometabolic risk factors among overweight and individuals with obesity

BackgroundObesity and hyperlipidemia are the two central metabolic disorders linked to non-communicable diseases (NCDs) that increase the risk of cardiovascular disease (CVD). Apart from dyslipidemia, the Atherogenic Index of Plasma (AIP), which is associated with dietary consumption, is another marker for predicting the risk of CVD. Healthy fat quality indicators may impact AIP. The purpose of this study is to ascertain whether there is any connection between Iranian obese people’s plasma and dietary indices and cardiometabolic risk factors.MethodsThis cross-sectional study, consisted of 645 overweight and obese participants. The study included assessments of body composition and anthropometric measurements. Dietary fatty acid consumption was evaluated using a validated Food Frequency Questionnaire (FFQ) containing 168 items. Additionally, biochemical parameters, including serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fasting serum glucose (FSG), and insulin levels, were measured using enzymatic methods. The lipid profile was quantified.ResultsFor participants in higher tertiles of the AIP, the percentage of men was significantly higher than women (men: 48.1%, women: 51.7%, p < 0.001). Additionally, individuals in higher tertiles of AIP had a higher waist-to-hip ratio (WHR) (mean WHR: 0.92 ± 0.05 vs. 0.86 ± 0.04 in lower tertile, p < 0.001). Participants in the highest tertile of AIP had higher systolic blood pressure (SBP: 132 ± 8 mmHg vs. 118 ± 6 mmHg in lower tertile, p < 0.001), total cholesterol (TC: 210 ± 15 mg/dL vs. 185 ± 12 mg/dL, p < 0.001), triglycerides (TG: 180 ± 20 mg/dL vs. 120 ± 15 mg/dL, p < 0.001), and glucose concentrations (fasting glucose: 105 ± 10 mg/dL vs. 90 ± 8 mg/dL, p < 0.001). Participants in the lower tertile of AIP had higher HDL cholesterol levels (HDL: 60 ± 5 mg/dL vs. 45 ± 4 mg/dL in higher tertile, p < 0.001). In the model for Thrombogenicity Index (TI), participants in the higher tertile had higher glucose concentrations (glucose: 110 ± 12 mg/dL vs. 95 ± 9 mg/dL in lower tertile, p = 0.04).ConclusionThis research introduces a novel field of investigation and emphasizes the possible importance of TI, AI, and AIP indices in regulating cardiometabolic risk factors.