Insulin Resistance Research Articles

Metabolic effects of heterocyclic amines on insulin‑induced AKT phosphorylation and gluconeogenic gene expression are modified by N-acetyltransferase 2 genetic polymorphism.

Heterocyclic amines (HCAs) are mutagens and carcinogens primarily generated when cooking meat at high temperatures or until well-done, and their major metabolic pathway includes hepatic N-hydroxylation via CYP1A2 followed by O-acetylation via N-acetyltransferase 2 (NAT2). NAT2 expresses a well-defined genetic polymorphism in humans resulting in rapid and slow acetylators. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes. We assessed the effect of some of the most common HCAs found in cooked meat, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, on insulin signaling and gluconeogenic gene expression in cryopreserved human hepatocytes characterized by their NAT2 genotype and phenotype to investigate the role of NAT2 genetic polymorphism in HCA-induced metabolic dysregulation. HCA treatment significantly reduced insulin-induced protein kinase B phosphorylation and significantly increased expression of genes involved in gluconeogenesis (G6PC, PCK1, FOXO1, and PPARA) in cryopreserved human hepatocytes from rapid but not from slow acetylators. The findings suggest that NAT2 genetic polymorphism modifies HCA-induced insulin resistance and gluconeogenic gene expression, implying that individuals with rapid acetylator phenotype may be at greater risk of dysregulated glucose homeostasis following exposure to HCAs.

The role of Anti-Müllerian hormone in women health.

Anti-Müllerian hormone (AMH), also known as Müller duct inhibitory factor and primarily known for its role in sexual differentiation. In female fetuses, AMH production by granulosa cells begins around the 36th week of gestation and continues in women until menopause. It is becoming more significant in the endocrine and gynecological diagnosis of adult women. The suppressive effect of AMH on follicle-stimulating hormone (FSH)-induced aromatase production likely plays a role in hyperandrogenism in polycystic ovary syndrome (PCOS) and may increase insulin resistance. Female adolescent with type 1 diabetes (T1D) have an increased likelihood of developing PCOS, but it is not known whether they also show elevated AMH levels. The elevated AMH levels observed in prepubertal girls with T1D suggest that there are more small follicles in their ovaries, probably in response to insulin treatment. Elevated levels of androgens and anti-Müllerian hormone have been previously reported in non-pregnant women with diabetes. The increased AMH concentrations can be associated with reduced systemic inflammation [lower c-reactive protein (CRP) values], irrespective of the type of diet and greater insulin sensitivity in old obese males. AMH can also serve as a valuable marker for granulosa cell tumors (folliculomas) and their recurrence. In these clinical scenarios, AMH levels can be significantly elevated and correspond with the size of the tumor.

Heme oxygenase, biliverdin reductase, and bilirubin pathways regulate oxidative stress and insulin resistance: a focus on diabetes and therapeutics.

Metabolic and insulin-resistant diseases, such as type 2 diabetes mellitus (T2DM), have become major health issues worldwide. The prevalence of insulin resistance in the general population ranges from 15.5% to 44.6%. Shockingly, the global T2DM population is anticipated to double by 2050 compared with 2021. Prior studies indicate that oxidative stress and inflammation are instrumental in causing insulin resistance and instigating metabolic diseases. Numerous methods and drugs have been designed to combat insulin resistance, including metformin, thiazolidinediones (TZDs), sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP1RA), and dipeptidyl peptidase 4 inhibitors (DPP4i). Bilirubin is an antioxidant with fat-burning actions by binding to the PPARα nuclear receptor transcription factor, improving insulin sensitivity, reducing inflammation, and reversing metabolic dysfunction. Potential treatment with antioxidants like bilirubin and increasing the enzyme that produces it, heme oxygenase (HMOX), has also gained attention. This review discusses the relationships between bilirubin, HMOX, and insulin sensitivity, how T2DM medications affect HMOX levels and activity, and potentially using bilirubin nanoparticles to treat insulin resistance. We explore the sex differences between these treatments in the HMOX system and how bilirubin levels are affected. We discuss the emerging concept that bilirubin bioconversion to urobilin may have a role in metabolic diseases. This comprehensive review summarizes our understanding of bilirubin functioning as a hormone, discusses the HMOX isoforms and their beneficial mechanisms, analyzes the sex differences that might cause a dichotomy in responses, and examines the potential use of HMOX and bilirubin nanoparticle therapies in treating metabolic diseases.

Kidney Dysfunction Prediction by Serum Adropin in Type 2 Diabetes Iraqi Patients

Abstract Background: Diabetic nephropathy (DN) is a problem that arises from microvascular complications with type 2 diabetes mellitus (T2DM). It especially denotes the deterioration of renal function. Adropin, a regulatory peptide hormone, has attracted interest for its potential role in regulating metabolism, specifically glucose metabolism and insulin resistance. Objective: To assess Adropin’s role in the identification and severity of T2DM nephropathy. Methods: A cross-sectional study which involved an 88 patients with DN was conducted in the National Diabetes Center/Mustansiriyah University during the period from October 2023 to April 2024. Body mass index, blood analysis for sugar levels, lipid profile, renal function test, and albumin to creatinine ratio in urine were conducted. In addition, the content of human adropin was evaluated using an enzyme-linked immunosorbent assay. Results: Much more fasting blood sugar, glycated hemoglobin, insulin, homeostasis model assessment insulin resistance, cholesterol, triglycerides, low-density lipoprotein (LDL) and very LDL, urea, and creatinine were found in the microalbuminuria and macroalbuminuria groups of DN patients than in the normoalbuminuria group. The amount of adropin in the blood was lowered in people with microalbuminuria and macroalbuminuria (245.91 ± 59.47 and 179.86 ± 51.96 pg/ml, respectively) than in people with normoalbuminuria (377.97 ± 98.69 pg/ml) as well. While the subject attempts to identify the difference between the groups of DN, adropin works very well and is very sensitive. Conclusion: This study establishes a correlation between reduced adropin levels and impaired kidney function in individuals diagnosed with T2DM. Adropin content in the serum is able to serve as a biomarker for the early recognition of DN, by its role in glucose metabolism and insulin resistance.

Deubiquitinating enzyme USP2 alleviates muscle atrophy by stabilizing PPARγ.

Insulin resistance, a hallmark of type 2 diabetes, accelerates muscle breakdown and impairs energy metabolism. However, the role of Ubiquitin Specific Peptidase 2 (USP2), a key regulator of insulin resistance, in sarcopenia remains unclear. Peroxisome proliferator activated receptor γ (PPARγ) plays a critical role in regulating muscle atrophy. This study investigates the role of deubiquitinase USP2 in mitigating muscle atrophy. Our findings revealed reduced USP2 expression in skeletal muscles of patients with type 2 diabetes. In mouse models of diabetes- and dexamethasone (DEX)-induced muscle atrophy, USP2 expression was downregulated in skeletal muscles. Usp2 knockout exacerbated muscle loss and functional impairment induced by diabetes or DEX. Moreover, skeletal muscle-specific Usp2 knockout further aggravated muscle loss and functional impairment induced by diabetes. Local injection of AAV-Usp2 into the gastrocnemius muscles of diabetic mice increased muscle mass, and improved skeletal muscle performance and endurance. It enhanced insulin sensitivity in diabetic mice, shown by lower fasting serum glucose and insulin levels and better glucose tolerance. Mechanistic analysis showed USP2 directly interacted with PPARγ by deubiquitinating it, stabilizing its protein levels, enhancing insulin signaling and sensitivity, and maintaining muscle mass. Loss of PPARγ abolishes the regulatory effects of USP2 on insulin sensitivity and muscle atrophy. MYOD1 activates USP2 transcription by binding to its promoter region. This study demonstrates the protective role of USP2 in mitigating muscle atrophy by stabilizing PPARγ through deubiquitination, particularly in models of diabetic and DEX-induced muscle atrophy. Targeting the USP2-PPARγ axis may offer promising therapeutic strategies for metabolic disorders and sarcopenia.

Hallmarks of Quercetin Benefits as a Functional Supplementary in the Management of Diabetes Mellitus-Related Maladies: From Basic to Clinical Applications.

Quercetin (QE), a particular flavonoid, is well known for its medicinal effects, including anti-oxidant, hypoglycemic, and anti-inflammatory effects. In this review, the findings of QE effects on diabetes STZinduced, alloxan-induced, and its complications have been summarized with a particular focus on in vitro, in vivo, and clinical trials. Consequently, QE mediates several mechanisms, including ameliorating tumor necrosis factor (TNF)-α, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1β, IL-8, and IL-10 expression, increasing insulin glucose uptake to inhibit insulin resistance. Moreover, QE stimulates insulin secretion and attenuates insulin resistance through various pathways, namely transient KATP channel, motivating peroxisome proliferator-activated receptor expression, increasing glucose transporter-4, and decreasing inducible nitric oxide synthase in skeletal muscle. QE has protective effects on the complications caused by diabetes, such as polycystic ovary syndrome, high-fat diet-induced obesity, diabetic-induced hepatic damage, vascular inflammation, nephropathy, and neuropathy.

Longitudinal Associations of PFAS Exposure With Insulin Sensitivity and β-Cell Function Among Hispanic Women With Gestational Diabetes Mellitus History.

We investigated associations between per- and polyfluoroalkyl substances (PFAS) and changes in diabetes indicators from pregnancy to 12 years after delivery among women with a history of gestational diabetes mellitus (GDM). Eighty Hispanic women with GDM history were followed from the third trimester of pregnancy to 12 years after delivery. Oral and intravenous glucose tolerance tests were conducted during follow-up. Plasma PFAS concentrations were measured at the third trimester of pregnancy and first postpartum visit. A linear mixed-effects model was used to analyze associations between PFAS and trajectories of diabetes indicators, adjusted for age, breastfeeding status, daily total calorie intake, and body fat percentage. Increased 2-(N-methyl-perfluorooctane sulfonamido) acetate level was associated with faster increase in concentrations of fasting glucose (P = 0.003). Increased perfluorononanoate (PFNA) and linear perfluorooctanoate (n-PFOA) concentrations were associated with faster increase in fasting insulin concentrations (P = 0.04 for PFNA; P = 0.02 for n-PFOA) and faster decrease in acute insulin response to glucose (P = 0.04 for PFNA; P = 0.02 for n-PFOA). PFAS exposure is associated with glucose intolerance, insulin resistance, and β-cell dysfunction, thus increasing type 2 diabetes risk.

Utility of the C-peptide/insulin molar ratio for distinguishing type A insulin resistance syndrome from type 2 diabetes.

Type A insulin resistance syndrome (IRS), characterized by impaired insulin receptor function due to variants of the insulin receptor gene, manifests as severe insulin-resistant diabetes. Differentiation of type A IRS from type 2 diabetes on the basis of hyperinsulinemia can be challenging. Given the association between insulin receptor dysfunction and reduced insulin clearance, we evaluated the potential of the circulating C-peptide reactivity (CPR)/immunoreactive insulin (IRI) molar ratio, a marker of insulin clearance, for distinguishing type A IRS from type 2 diabetes. We retrospectively analyzed CPR and IRI levels measured during a 75-g oral glucose tolerance test (OGTT) in 18 individuals with type A IRS and 126 with type 2 diabetes. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic performance of the CPR/IRI molar ratio and IRI levels. IRI levels were significantly higher and the CPR/IRI molar ratio significantly lower in individuals with type A IRS compared with those with type 2 diabetes. The area under the ROC curve for the CPR/IRI molar ratio at baseline, 1 hour, and 2 hours after OGTT initiation was 0.997 (sensitivity 100%, specificity 99.2%), 0.999 (sensitivity 100%, specificity 97.6%), and 0.997 (sensitivity 100%, specificity 95.1%), respectively. The CPR/IRI molar ratio demonstrated robust diagnostic performance regardless of body mass index or hyperinsulinemia severity. The CPR/IRI molar ratio, both at baseline and during OGTT, exhibited higher sensitivity and specificity than IRI levels alone for distinguishing type A IRS from type 2 diabetes. This ratio may serve as a reliable clinical marker for early and accurate diagnosis of type A IRS.

Cognitive dysfunction in diabetes - the 'forgotten' diabetes complication: a narrative review.

In addition to peripheral neuropathy of various kinds, diabetes can also cause central neuropathy, which among other things can manifest itself as premature cognitive dysfunction, often linked to vascular dysfunction. Although the link between diabetes and cognitive dysfunction was discovered more than 100 years ago and has important clinical implications, this diabetes complication remains relatively unknown. Recent years have seen research that has clarified cerebral insulin resistance and defective insulin signaling as examples of pathogenic factors behind this cognitive impairment in diabetes. We provide a narrative review of select and contemporary publications with relevance for the interface between diabetes/prediabetes and cognitive function. Recently published studies show that physical activity can reverse insulin resistance in the brain as well as cognitive impairment and pathological appetite regulation. Pharmacological interventions with, for example, nasal insulin, GLP-1 receptor agonists, SGLT-2 inhibitors, or PPAR-γ agonists have also shown promising results. Optimization of lifestyle factors (e.g. physical activity), as well as several pharmaceutical agents already in clinical use against diabetes, have shown promising results in improving cognitive function in diabetic patients. An important task for primary health care, where most patients with type 2 diabetes are diagnosed, treated, and followed, is to increase awareness and early detection of cognitive dysfunction in these patients for optimizing risk factor control.

Glucose Metabolic Abnormalities and Their Interaction With Defective Phosphate Homeostasis in Tumor-induced Osteomalacia.

Phosphate homeostasis was compromised in tumor-induced osteomalacia (TIO) due to increased fibroblast growth factor 23 (FGF23) secretion. Nevertheless, the glucose metabolic profile in TIO patients has not been investigated. This work aimed to clarify the glucose metabolic profiles in TIO patients and explore their interaction with impaired phosphate homeostasis. 20 TIO patients, 20 individuals with normal glucose tolerance, and 20 patients with type 2 diabetes mellitus (DM) were enrolled and underwent an oral glucose tolerance test (OGTT). Serum phosphate and FGF23 concentration were monitored during OGTT. In patients with TIO, 60% (12/20) exhibited impaired glucose tolerance (IGT) and 5% (1/20) had type 2 DM. Those with IGT or type 2 DM experienced more ambulatory difficulties (69.2% vs 42.9%), lower phosphate concentrations (0.43 ± 0.10 vs 0.53 ± 0.10, P = .042), and lower calcium concentrations (2.20 ± 0.08 vs 2.30 ± 0.40, P = .001) compared to TIO patients without these conditions. According to correlation analysis, serum phosphate levels were negatively correlated with plasma glucose levels at 60 minutes (P < .001), fasting plasma insulin levels (P < .05), and homeostasis model assessment for insulin resistance (P < .05). Those with high FGF23 levels had a higher glucose level at 60 minutes (10.5 [9.3, 12.3] vs 7.3 [6.4, 10.1], P = .048) than that of low group. After glucose loading, both FGF23 and phosphate levels exhibited a decreasing trend. The development of diabetes in TIO patients may be predisposed by ambulatory issues, low phosphate, and elevated FGF23 levels. Dysglycemia might further aggravate hypophosphatemia.

Association between enteral carboxymethyllysine intake and daily glycemic variability in critically ill adults: A retrospective cohort study.

Advanced glycation end-products (AGEs) can enter patients' circulation through exogenous sources, such as enteral nutrition formulae. Circulating AGEs, specifically carboxymethyllysine, can promote insulin resistance and activation of pro-inflammatory pathways leading to oxidative stress, cell death, and organ failure. Suboptimal kidney function increases the risk of elevated circulating AGEs because levels are controlled through urinary excretion. Our aim was to determine associations between carboxymethyllysine intake and glycemic control as well as clinical outcomes in critically ill patients and explore these in the subset of patients with an acute kidney injury (AKI). This was a retrospective cohort study. Data were extracted from electronic medical records. Patients were eligible if they were ≥18 years and received enteral nutrition, with known carboxymethyllysine content, for ≥3 days. AKI was defined using the Kidney Disease: Improving Global Outcomes guidelines. Linear and logistic regression models were used to determine adjusted associations. Between 2015 and 2021, 2636 patients met the eligibility criteria, with 848 (32%) patients having an AKI. Most were male (n = 1752, 67%) with a median (interquartile range) Acute Physiology And Chronic Health Evaluation III score of 59 (45-77). For every 10-μmol increase in carboxymethyllysine provision, mean blood glucose increased by 0.05 mmol (95% CI, 0.03-0.07), and the odds of dying increased by 16% (odds ratio = 1.16; 95% CI, 1.06-1.27). A subgroup analysis indicated these associations persisted in patients with AKI but not in those without. Carboxymethyllysine intake was associated with increased mean blood glucose and odds of dying in our study cohort.

Striving for early effective glycaemic and weight management in type 2 diabetes: A narrative review.

Despite the recognition by key guidelines that achieving early glycaemic control has important benefits in individuals with type 2 diabetes (T2D) and that addressing excess adiposity is one of the central components of comprehensive person-centred T2D care, a substantial proportion of individuals with T2D do not meet their metabolic treatment goals. Prior treatment paradigms were limited by important treatment-associated risks such as hypoglycaemia and body weight gain. Therefore, a more conservative, sequential approach to treatment was typically utilized. One potential consequence of this approach has been a missed opportunity to achieve a 'legacy effect', where early treatment to reach glycaemic targets is associated with enduring long-term benefits in T2D. Additionally, while previous treatment approaches have addressed core defects in T2D, including insulin resistance and β-cell function decline, they have been unable to address one of the underlying causal abnormalities-excess adiposity. Here, we review currently available evidence for the beneficial long-term effects of early glycaemic control and management of body weight in people with T2D and discuss potential next steps.

An insight on the additive impact of type 2 diabetes mellitus and nonalcoholic fatty liver disease on cardiovascular consequences.

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are associated with a multifactorial complicated aetiology that is often coexisting and has a strong and distinct connection with cardiovascular diseases (CVDs). In order to accomplish effective and appropriate therapeutic strategies, a deeper understanding of the bidirectional interaction between NAFLD patients, NAFLD patients with T2DM, and NAFLD patients with CVDs is required to control the concomitant rise in prevalence of these conditions worldwide. This article also aims to shed light on the epidemiology and mechanisms behind the relationship between T2DM, NAFLD and the related cardiovascular consequences. Literature was collected from PubMed, Medline, Embase, Web of Science and Google scholar from inception to June, 2024. For surveying literature different combinations and formats of terms including NAFLD, NASH, T2DM and CVDs were used. In the recent decade, clinical and epidemiological studies have been conducted and provide strong evidence that NAFLD is closely linked with CVD progression along with associated morbidity and mortality in both patients with and without T2DM. Several mechanistic approaches contribute to cardiovascular consequences and abnormalities in cardiac biomarkers in T2DM and NAFLD patients, including adipose tissue malfunction, mitochondrial dysfunction, the microbiota, genetic and epigenetic alterations contributing to insulin resistance, glucotoxicity and lipotoxicity. The study reveals a complex interplay between diabetes, hepatic and cardiovascular complications, leading to significant morbidity and mortality in diabetic and NAFLD patients. This pandemic necessitates further research to identify mitigating variables and develop effective treatment approaches.

Investigating the Roles of Brain-Derived Neurotrophic Factor, Vitamin D, and Insulin Resistance in Vitiligo Patients

Background: Vitiligo is a skin condition where skin loses its color, presenting as macules which are smooth white patches. It is considered to affect 1% of the world’s population and is associated with various factors such as autoimmunity, oxidative stress, and some mosquito psychological comorbities. Reduced levels of brain derived neurotrophic factor (BDNF) and vitamin D in addition to insulin resistance have also been impart in this disorder. Objective: The objective of this study was to determine the degree of involvement of BDNF, insulin, and vitamin D on the causation and course of vitiligo. Methods: A case control study was where 90 subjects were enrolled; 45 diagnosed with vitiligo and 45 were healthy control subjects from the dermatology clinic. Serum level of BDNF, insulin, vitamin D, and other metabolic markers were taken for evaluation through Enzyme linked immunosorbent assay (ELISA) tests. The activity and severity of the disease were evaluated using VIDA and VASI scores in that order. The parameters were then compared through statistical analysis (t-test and Pearson correlation) while the diagnostic accuracy of BDNF was evaluated with the ROC curve analysis. Results: With respect to mean serum level findings, BDNF and vitamin D were significantly lower in the vitiligo patients compared to the controls (p&lt;0.05). Conversely, insulin, fasting blood glucose FBG, and HOMA-IR levels in the patient group were significantly increased (p&lt;0.05). The diagnostic potential of BDNF was poor with AUC=40%. Furthermore, there were significant relationships discovered between the serum levels and duration as well as severity and activity scores of the disease. Conclusion: In reference to the above investigation, the three potential targets may be insulin resistance, BDNF, and deficient Vitamin D. These may be factors in the explanation of the pathophysiology of vitiligo. These biomarkers may be useful for strategizing therapy, disease management, and the psychological disease that accompanies vitiligo.

Risk of Insulin Resistance in 44,939 Spanish Healthcare Workers: Association with Sociodemographic Variables and Healthy Habits

Introduction: Insulin resistance (IR) is a highly prevalent pathophysiological entity implicated in the development of a wide variety of metabolic, cardiovascular, and endocrine disorders. The aim of this study is to assess the association between sociodemographic variables and healthy habits with IR risk scales. Methodology: This dual study, incorporating both longitudinal-retrospective and cross-sectional designs, analyzed healthcare workers across four professional categories (physicians, nurses, healthcare technicians, and auxiliary personnel). It examined the association of age, sex, professional category, smoking status, physical activity, and adherence to the Mediterranean diet with elevated scores on insulin resistance risk scales. Results: All the variables analyzed were associated with the presence of elevated values of the IR scales, with age, sex, and physical activity showing the strongest association (reflected in the odds ratio values). Conclusions: The profile of an individual with a higher risk of presenting elevated values of the IR risk scales would be an elderly male auxiliary health worker who is a smoker and is physically inactive, with a low adherence to the Mediterranean diet.

Markers for Pressure Injury Risk in Individuals with Chronic Spinal Cord Injury: A Pilot Study.

To identify markers associated with pressure injury (PrI) history in individuals with spinal cord injury (SCI) using two approaches: skin blood flow (SBF) response toward localized heating, and serum marker for insulin resistance. For this cross-sectional, observational study of adults with chronic traumatic SCI at T12 and above, researchers recruited two groups of participants: with history of PrI (group 1), and without history of PrI (group 2). The study protocol included obtaining fasting blood samples and measurement of SBF at bilateral heels with localized heating of 42 °C for 30 minutes from all participants. Primary SBF outcomes were initial peak and plateau SBF normalized to baseline SBF. The primary outcome for insulin resistance was Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), calculated from fasting plasma glucose and insulin. Secondary outcomes included demographic and SCI information. Researchers used the Fisher exact test and Wilcoxon-Mann-Whitney test to compare the intergroup difference of categorical and continuous variables, respectively. Sixteen adults completed this study (group 1, n = 7; group 2, n = 9). In comparison with group 2, group 1 had significantly higher HOMA-IR (3.90 ± 0.71 vs 1.45 ± 0.71), suggesting higher insulin resistance, and longer duration of injury (22.54 ± 7.24 vs 7.98 ± 6.58 years). There were no between-group differences in SBF or other secondary outcomes. HOMA-IR is a novel serum index associated with PrI history in persons with chronic SCI. Future longitudinal study is warranted to examine the role of insulin resistance in increasing PrI risk for the SCI population.

The Epigenetic Role of Nutrition Among Children and Adolescents: A Systematic Literature Review

Background/Objectives: Recent research has focused on the study of the epigenetic role of nutrition as a tool which is expected to introduce new perspectives in the field of disease prevention and management. Although maternal nutrition is one of the best-studied mechanisms of epigenetic modifications of the fetus/newborn, less is known on the impact of childhood/adolescent nutrition on the regulation of epigenetic mecha-nisms after the first year of life. The aim of the present study was the assessment of the epigenetic role of nutrition in the health and development of children and adolescents. Methods: A systematic review was performed according to the Preferred Reported Items for Systematic Reviews and Meta-analyses guidelines in five databases (PubMed, Cochrane, Science Direct, Scopus, and Google Scholar) up to 31 October 2024, which yielded 17 eligible studies. The Newcastle–Ottawa Scale and the Cochrane Collabora-tion Risk of Bias-2 tool were used for the evaluation of risk of bias in observational studies and randomized trials, respectively. Results: Three studies investigated the epi-genetic modifications due to lifestyle interventions combining changes both in diet and physical activity; the remaining 14 studies examined the role of dietary nutrients in the regulation of epigenetic mechanisms in various health conditions, such as Angelman’s syndrome, parenteral nutrition in Intensive Care Units, attention deficit hyperactivity disorder, risk of cardiovascular diseases, asthma or food sensitization, obesity, insulin resistance, and type 2 diabetes or evaluated epigenetic markers as new tools for the comprehension and prediction of the participants’ response to nutritional interven-tions. Conclusions: The important impact of diet on the regulation of epigenetic mech-anisms and the expression of various genes and gene pathways could be utilized for personalized nutritional interventions in various pediatric health conditions.

Phenome-wide associations of sleep characteristics in the Human Phenotype Project.

Sleep tests commonly diagnose sleep disorders, but the diverse sleep-related biomarkers recorded by such tests can also provide broader health insights. In this study, we leveraged the uniquely comprehensive data from the Human Phenotype Project cohort, which includes 448 sleep characteristics collected from 16,812 nights of home sleep apnea test monitoring in 6,366 adults (3,043 male and 3,323 female participants), to study associations between sleep traits and body characteristics across 16 body systems. In this analysis, which identified thousands of significant associations, visceral adipose tissue (VAT) was the body characteristic that was most strongly correlated with the peripheral apnea-hypopnea index, as adjusted by sex, age and body mass index (BMI). Moreover, using sleep characteristics, we could predict over 15% of body characteristics, spanning 15 of the 16 body systems, in a held-out set of individuals. Notably, sleep characteristics contributed more to the prediction of certain insulin resistance, blood lipids (such as triglycerides) and cardiovascular measurements than to the characteristics of other body systems. This contribution was independent of VAT, as sleep characteristics outperformed age, BMI and VAT as predictors for these measurements in both male and female participants. Gut microbiome-related pathways and diet (especially for female participants) were notably predictive of clinical obstructive sleep apnea symptoms, particularly sleepiness, surpassing the prediction power of age, BMI and VAT on these symptoms. Together, lifestyle factors contributed to the prediction of over 50% of the sleep characteristics. This work lays the groundwork for exploring the associations of sleep traits with body characteristics and developing predictive models based on sleep monitoring.

Kdm2a inhibition in skeletal muscle improves metabolic flexibility in obesity.

Skeletal muscle is a critical organ in maintaining homoeostasis against metabolic stress, and histone post-translational modifications are pivotal in those processes. However, the intricate nature of histone methylation in skeletal muscle and its impact on metabolic homoeostasis have yet to be elucidated. Here, we report that mitochondria-rich slow-twitch myofibers are characterized by significantly higher levels of H3K36me2 along with repressed expression of Kdm2a, an enzyme that specifically catalyses H3K36me2 demethylation. Deletion or inhibition of Kdm2a shifts fuel use from glucose under cold challenge to lipids under obese conditions by increasing the proportion of mitochondria-rich slow-twitch myofibers. This protects mice against cold insults and high-fat-diet-induced obesity and insulin resistance. Mechanistically, Kdm2a deficiency leads to a marked increase in H3K36me2 levels, which then promotes the recruitment of Mrg15 to the Esrrg locus to process its precursor messenger RNA splicing, thereby reshaping skeletal muscle metabolic profiles to induce slow-twitch myofiber transition. Collectively, our data support the role of Kdm2a as a viable target against metabolic stress.

Research hotspots and trends in gut microbiota and nonalcoholic fatty liver disease: A bibliometric study.

Recent research indicates that the intestinal microbial community, known as the gut microbiota, may play a crucial role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). To understand this relationship, this study used a comprehensive bibliometric analysis to explore and analyze the currently little-known connection between gut microbiota and NAFLD, as well as new findings and possible future pathways in this field. To provide an in-depth analysis of the current focus issues and research developments on the interaction between gut microbiota and NAFLD. In this study, all data were collected from the Web of Science Core Collection, and the related searches were completed on one day (February 21, 2024). The data were stored in plain text format to facilitate subsequent analysis. VOSviewer 1.6.20 and CiteSpace 6.1R6 Basic were used for knowledge graph construction and bibliometric analysis. The study included a total of 1256 articles published from 2013 to 2023, and the number of published papers demonstrated an upward trend, reaching a peak in the last two years. The University of California, San Diego held the highest citation count, while Shanghai University of Traditional Chinese Medicine in China led in the number of published works. The journal "Nutrients" had the highest publication count, while "Hepatology" was the most frequently cited. South Korean author Suk Ki Tae was the most prolific researcher. The co-cited keyword cluster labels revealed ten major clusters, namely cortisol, endothelial dysfunction, carbohydrate metabolism, myocardial infarction, non-alcoholic steatohepatitis, lipotoxicity, glucagon-like peptide-1, non-islet dependent, ethnicity, and microRNA. Keyword outbreak analysis highlighted metabolic syndrome, hepatic steatosis, insulin resistance, hepatocellular carcinoma, cardiovascular disease, intestinal permeability, and intestinal bacterial overgrowth as prominent areas of intense research. Through the quantitative analysis of relevant literature, the current research focus and direction of gut microbiota and NAFLD can be more clearly understood, which helps us better understand the pathogenesis of NAFLD, and also opens up innovative solutions and strategies for the treatment of NAFLD.