Hormone and Metabolic Research最新文献

Aging is marked by a gradual decline in multiple physiological functions, increasing the risk of age-related disorders. Multiple factors have been identified as contributors to aging, many of which are regulated by the hypothalamus. Growth hormone-releasing hormone (GHRH) produced in the hypothalamus is a key regulator of growth hormone (GH) secretion. With aging, both GHRH and GH levels decline, leading to muscle loss, increased fat accumulation, metabolic dysregulation, and cognitive impairments. GH replacement therapy has been explored as a potential intervention to counteract these effects; however, its long-term use is associated with significant risks, including metabolic disturbances, cardiovascular complications, and potential cancer promotion. In contrast, studies suggest that GHRH-based therapies can improve body composition, muscle strength, cognitive function, and cardiovascular health while avoiding the risks linked to direct GH administration. Additionally, preclinical findings indicate that GHRH agonists may offer cardioprotective and immunomodulatory benefits. In this review, we summarize current knowledge on the roles of GHRH and GH in aging, highlight the limitations of GH-based therapies, and discuss the potential of GHRH-based approaches in mitigating age-related decline and improving health span.

Systemic immune-inflammatory indices derived from routine complete blood counts are useful markers of systemic inflammation across various conditions. Currently, double filtration plasmapheresis is used to lower lipid levels and remove pro-inflammatory mediators; however, its effects on systemic immune-inflammatory indices are underreported. A retrospective analysis of patients undergoing two double filtration plasmapheresis sessions for hypercholesterolemia or hyperlipoproteinemia(a) at a single center was conducted between April and July 2025. Complete blood count-derived immune-inflammatory indices and lipid profiles were measured immediately before and after the first and second double filtration plasmapheresis sessions, respectively. Intra-individual comparisons were performed using the Wilcoxon signed-rank test. Double filtration plasmapheresis performed with the Inuspheresis System significantly reduced the neutrophil-to-lymphocyte ratio (p=0.040), platelet-to-lymphocyte ratio (p=<0.001), systemic immune-inflammatory index (p=0.008), and aggregate index of systemic inflammation (p=0.048), while significantly increasing lymphocyte-to-monocyte ratio (p=<0.001); systemic inflammation response index did not change significantly. Expected reductions were also observed in total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and lipoprotein(a), all with p <0.001. In addition to its lipid-lowering effects, double filtration plasmapheresis modulated short-term systemic immune-inflammatory indices, indicating potential utility for these metrics as surrogate markers of acute systemic inflammation and immunomodulation. Given their availability from routine complete blood counts, monitoring these indices could aid individualized patient assessment during double filtration plasmapheresis. These results may also help refine personalized care in patients with low-grade inflammation and aging-related immune dysfunction.

Cardiovascular and metabolic disorders, particularly diabetes and obesity, are highly prevalent in the Middle East and North Africa (MENA) region, exhibiting some of the highest global incidence rates. These conditions significantly increase the severity of infectious diseases, notably COVID-19, leading to a rise in long-COVID cases among affected individuals. Furthermore, the MENA region's extreme temperatures exacerbate cardiovascular issues by elevating heart rates and blood pressure, increasing dehydration and blood viscosity. Extracorporeal therapies, such as apheresis, effectively reduces plasma lipids and inflammatory markers. Furthermore, apheresis has shown promise in reducing autoantibodies associated to long-COVID. Our previous research indicated that apheresis alleviates symptoms in patients with long-COVID and chronic fatigue syndrome. In this study, we treated 24 male patients from the MENA region suffering from chronic fatigue and/or different metabolic diseases such as diabetes, dyslipidemia, or obesity, using double filtration plasmapheresis. Comprehensive plasma analyses were performed before and after apheresis to assess lipid profiles, inflammatory markers, and autoantibodies, revealing significant changes following the procedure. Genetic analyses on a subgroup of the patients showed no mutations in the LDLR, APOB, APOE, PCSK9, LIPA, and LDLRAP1 genes known to be associated with predispositions to monogenic lipid disorders. However, all patients in this subgroup demonstrated an intermediate to high likelihood that their elevated lipid levels have a polygenic basis. These findings suggest that implementing apheresis in the MENA region could significantly improve health outcomes and life expectancy for affected individuals.

Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, is approved for the treatment of type 2 diabetes mellitus and heart failure. Its known ability to enhance mitochondrial adenosine triphosphate production and improve cardiac function led us to investigate whether blood adenosine triphosphate levels could serve as a predictive biomarker for treatment response. This prospective study included 120 patients from Kyrgyzstan: 49 with type 2 diabetes mellitus, 43 with heart failure, and 28 with both type 2 diabetes mellitus and heart failure. The mean age of the study population was 63.9±7.1 years, with no significant age difference between groups. Patients received oral empagliflozin at a dose of either 10 or 25 mg daily for 12 weeks. Adenosine triphosphate activity was measured in erythrocytes from whole blood samples before and after treatment. In vitro assays were also performed, incubating patient blood samples with empagliflozin at concentrations of 0.1, 1, and 10 µM. In patients with type 2 diabetes mellitus, empagliflozin significantly reduced body mass index (p=0.001), though HbA1c levels remained unchanged. Among heart failure patients, treatment resulted in a significant increase in left ventricular ejection fraction (p=0.028) and a decrease in B-type natriuretic peptide levels (p=0.01). Blood adenosine triphosphate concentrations increased significantly following empagliflozin treatment in both type 2 diabetes mellitus and heart failure groups. Proteomic analysis identified 12 differentially expressed proteins-ADIPOQ, ARG1, CST3, CPPED1, GSTO1, FN1, ITIH4, LCN2, LCP1, MIF, PCMT1, and SERPINA3-that are functionally linked to type 2 diabetes mellitus and/or heart failure pathophysiology. Our data suggest that blood adenosine triphosphate activity may serve as a potential biomarker for clinical response to empagliflozin in patients with type 2 diabetes mellitus and heart failure. Further studies are warranted to validate these exploratory findings and to evaluate the sensitivity, specificity, and predictive value of blood adenosine triphosphate as a biomarker in these populations.

Thyroid hormones, primarily triiodothyronine (T3) and thyroxine (T4), are critical regulators of metabolic rate, mitochondrial function, and cellular repair mechanisms. Emerging evidence suggests that thyroid status may significantly influence aging trajectories and longevity through modulation of key cellular pathways. This review explores the role of thyroid hormones in aging biology, with a focus on their interaction with longevity-associated signaling pathways and the hallmarks of aging. Both physiological and subclinical thyroid states in the context of healthspan, cognitive preservation, metabolic resilience, and mitochondrial integrity are explored. A narrative synthesis of human and animal studies was conducted, including mechanistic, epidemiologic, and clinical data, to evaluate how thyroid hormone levels affect aging pathways such as mechanistic target of rapamycin, AMP-activated protein kinase, IGF-1, sirtuins, FOXO transcription factors, and mitochondrial biogenesis. Thyroid hormones modulate several hallmarks of aging, including mitochondrial dysfunction, genomic instability, epigenetic drift, and deregulated nutrient sensing. T3 enhances mitochondrial respiration and autophagy while interacting with mechanistic target of rapamycin and AMP-activated protein kinase to regulate energy balance. Altered thyroid function-particularly subclinical hypothyroidism-has been paradoxically associated with increased longevity in some centenarian cohorts, possibly due to reduced oxidative metabolism. However, overt thyroid dysfunction is linked to increased metabolic risk in aging populations. Thyroid hormones serve as metabolic gatekeepers that influence both cellular aging and organismal longevity. A deeper understanding of their role in aging pathways may inform novel strategies for promoting healthy aging, including thyroid hormone modulation and personalized endocrine optimization.

An independent association between insulin resistance and cancer has been consistently reported in humans. Patients with cancer display insulin resistance or its clinical manifestations, and this metabolic adaptation precedes the clinical diagnosis of cancer. Insulin resistance in cancer patients is associated with a metabolic switch from oxidative metabolism toward glycolysis that spares oxygen to be used in anabolic processes and facilitates the fast production of energy and intermediate metabolites required for the rapid proliferation of cancer cells. In malignant cells, glucose consumption via glycolysis occurs under normoxic conditions (aerobic glycolysis). Pathogenic mechanisms underlying insulin resistance in cancer patients include hypoxia-inducible factor-1 upregulation and overproduction of cytokines, such as interferon, interleukin-6, interleukin-18, and interleukin-1β. Deficit of 2-oxoglutarate (α-ketoglutarate) has been detected in cancer cells and may facilitate hypoxia-inducible factor-1 assembly and activity. Overproduction of cytokines in cancer patients follows activation of the immune system by abnormal nucleic acid variants. Anomalous DNA or RNA structures are recognized by immune sensors and stimulate signaling pathways that ultimately increase cytokine production. Likewise, interferon overproduction occurs in congenital disorders that feature ineffectively repaired DNA lesions, such as Werner syndrome, Bloom syndrome, mutations in DNA polymerase-δ1, and ataxia telangiectasia. These diseases cause simultaneous insulin resistance and a high tendency to develop cancer, highlighting the relationship between the two processes. Defectively repaired DNA injury endangers genomic integrity, predisposing to cancer, and activates the immune system to increase interferon production and subsequent insulin resistance. Hypoxia-inducible factor-1 and cytokines induce insulin resistance by suppressing peroxisome proliferator-activated-γ in the subcutaneous adipose tissue.

Metabolic syndrome is a complex condition characterized by central obesity, hyperglycemia, insulin resistance, inflammation, dyslipidemia and hypertension which predispose individuals toward diabetes and cardiovascular disorder. The aim of this review is to investigate some selected novel adipokines, myokines, and hepatokines whose secretion is affected by exercise and improves metabolic syndrome. According to epidemiological studies, the incidence of metabolic syndrome is expected to increase every year, which predisposes health organizations with big challenges. Regular exercise stands as a preventive tool for metabolic syndrome, not only by improving blood circulation, but also through alterations in exerkines. The proteins are secreted by adipose tissue (adipokines), skeletal muscles (myokines), liver (hepatokines) or other tissues during exercise. Interestingly, adipo-myo-hepatokines are categorized into inflammatory and anti-inflammatory peptides, and exercise either reduces or elevates them. The beneficial effects of exercise for various physiological systems, and more importantly prevention and treatment of metabolic syndrome, still have remained mysterious. According to the literature, some of the anti-inflammatory exerkines cooperate in the metabolic homeostasis of organisms by increasing blood flow, muscle mass, and glucose utilization and improving insulin sensitivity and fatty acid oxidation.

Non-alcoholic fatty liver disease is the most common form of chronic liver disease. However, effective pharmacotherapy is still lacking. Sodium-glucose cotransporter-2 inhibitors have been proven to improve non-alcoholic fatty liver disease in previous clinical trials. In this work, an updated systematic review and meta-analysis of randomized controlled trials were performed to evaluate the efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients with non-alcoholic fatty liver disease. A literature search of PubMed, Cochrane, Web of Science, Medline, and Embase was performed up to August 2024. Articles were sieved to determine eligible randomized controlled trials. Review Manager version 5.4 software was used to conduct the meta-analysis. A total of 21 randomized controlled trials with 1,311 participants were included. Compared with the controls, sodium-glucose cotransporter-2 inhibitor treatment significantly improved the controlled attenuation parameter, liver fat content, liver-to-spleen ratio, liver stiffness measurement, fibrosis-4 index, serum type IV collagen 7S level, serum alanine transaminase level, serum aspartate transaminase level, serum gamma-glutamyl transaminase level, fasting serum insulin level, homeostatic model assessment for insulin resistance, body weight, body mass index, visceral adipose tissue, and subcutaneous adipose tissue. The incidence of total adverse events was not significantly different between the sodium-glucose cotransporter-2 inhibition group and the control group. Sodium-glucose cotransporter-2 inhibitors can improve liver steatosis, liver fibrosis, liver enzymes, insulin resistance, and body composition in patients with non-alcoholic fatty liver disease. Sodium-glucose cotransporter-2 inhibitors are safe and well tolerated. Sodium-glucose cotransporter-2 inhibitors may become promising drugs for non-alcoholic fatty liver disease treatment.

Cardiovascular diseases are a leading cause of death globally. Early identification of individuals at elevated risk is essential for improving preventive measures and patient outcomes. Biomarkers like Galectin-1, leptin, and adiponectin are known to play roles in metabolic processes, with a low adiponectin/leptin ratio indicating a heightened cardiometabolic risk. However, the association between Galectin-1, leptin, adiponectin, and the adiponectin/leptin ratio with cardiovascular disease risk scores is not well understood. This study aims to assess these markers' correlation with cardiovascular disease risk and their potential utility as predictors. This cross-sectional study assessed 135 healthy adults through questionnaires and blood pressure measurements. Each participant's cardiovascular (CV) risk was estimated, with serum Galectin-1, adiponectin, and leptin levels measured. Comparisons of adipokine levels between age groups were conducted. The associations between variables were assessed, and linear regression was applied with cardiovascular risk score as the outcome. Statistical significance was set at p<0.05. After excluding fifteen individuals, 122 subjects (62 males, 60 females; mean age 43.8 yr) were included in the study. Leptin levels correlated positively with CV risk score and LDL levels in younger individuals, while the adiponectin/leptin ratio showed a negative correlation with low density lipoproetin (LDL) and CV risk scores across age groups. Smoking was a strong predictor of CV risk in younger participants, whereas diabetes, cholesterol/high-density lipoprotein ratio, and leptin were significant predictors in the middle-aged group (p<0.05). Among measured adipokines, leptin is as a key predictor of cardiovascular risk, alongside established factors like smoking, diabetes, and cholesterol/high-density lipoprotein ratio.

The triglyceride-glucose index, an indicator of insulin resistance, has emerged as a potential predictor of various cardiovascular diseases. However, the association between the triglyceride-glucose index and peripheral artery disease remains unclear. This meta-analysis sought to clarify the relationship between the triglyceride-glucose index and the incidence or prevalence of peripheral artery disease. A comprehensive search of the PubMed, Embase, and Web of Science databases was carried out to identify relevant observational studies published up to June 1, 2024. Inclusion criteria included studies on adult populations that evaluated the triglyceride-glucose index and reported peripheral artery disease outcomes. To assess the association between the triglyceride-glucose index and peripheral artery disease, risk ratios and 95% confidence intervals were computed using a random-effects model incorporating the impact of heterogeneity. Nine studies with a total of 37,761 participants were involved in the meta-analysis. The analysis revealed that individuals with a high triglyceride-glucose index had significantly increased odds of peripheral artery disease (risk ratio: 1.42, 95% confidence interval: 1.21-1.67, p < 0.001; I ²=55%). Sensitivity analyses performed by excluding one study at a time confirmed the robustness of these findings. Subgroup analyses demonstrated consistent associations across different study designs, populations, and methodological quality. Diabetic patients exhibited a stronger association (risk ratio: 1.38) compared to non-diabetic participants (risk ratio: 1.06, p _{subgroup difference}=0.006). In conclusion, a high triglyceride-glucose index is linked to peripheral artery disease, especially in people with diabetes. These results suggest that the triglyceride-glucose index could be used as a valuable marker for assessing peripheral artery disease risk in clinical practice.