Hormones-International Journal of Endocrinology and Metabolism最新文献

Purpose: This study explores the role of nuclear factor E2-related factor 2 (Nrf2) in regulating adipose tissue phenotype and its potential mechanisms for promoting aging resistance in 3T3-L1 adipocytes. The study aims to evaluate the impact of Nrf2 knockdown on adipose phenotype transformation, focusing on brown adipose tissue (BAT) and white adipose tissue (WAT) marker genes, as well as longevity-related factors.

Methods: 3T3-L1 preadipocytes were differentiated into adipocytes using a standard MDI regimen. Nrf2 expression was knocked down via siRNA transfection. Gene expression was assessed using quantitative real-time PCR (qPCR), and protein levels were analyzed using Western blotting.

Results: Nrf2 knockdown was confirmed by Western blot (p<0.001) and qPCR (p<0.001), showing a significant reduction in Nrf2 expression. Notably, this knockdown resulted in increased expression of BAT markers, including PGC-1α (p = 0.012), Dio2 (p = 0.020), and PRDM16 (p = 0.001), at both mRNA (PGC-1α [p = 0.012], Dio2 [p = 0.020], and PRDM16 [p = 0.001]) and protein (PGC-1α [p = 0.001]; Dio2 [p = 0.003]; PRDM16 [p = 0.007])levels. Conversely, WAT markers such as BMP4 (mRNA: p = 0.01; WB: p = 0.001), resistin (mRNA: p = 0.016; WB: p = 0.004), and Rb1 (mRNA: p = 0.03; WB: p = 0.003) were significantly downregulated. Additionally, levels of Cycs (mRNA: p = 0.024; WB: p = 0.037) and UCP1 (mRNA: p = 0.024; WB: p = 0.023) were elevated, indicating enhanced mitochondrial function and metabolic activity (P < 0.05). The knockdown also affected longevity-related proteins, Sirt1 (WB: p = 0.018) and AMPKα (WB: p = 0.021), underscoring Nrf2's role in metabolic regulation.

Conclusion: Nrf2 knockdown in 3T3-L1 adipocytes promotes a transition towards a brown adipose phenotype and enhances the expression of longevity-related factors, suggesting Nrf2 as a potential therapeutic target for addressing aging-related metabolic decline.

Objective: This study aims to identify hub genes associated with the onset and progression of Graves' disease (GD) with the goal of developing novel biomarkers to enhance diagnosis and improve patient outcomes.

Methods: mRNA profiles from thyroid tissue samples (24 GD vs. 24 normal controls) were obtained from GEO (GSE9340), ArrayExpress (E-MEXP-2612), and GTEx (Thyroid dataset). After batch correction via SVA algorithm, 366 differentially expressed genes (DEGs) were identified using limma. Functional enrichment, protein-protein interaction networks, and immune microenvironment analysis were performed. Hub genes were validated in clinical thyroid specimens (3 GD vs. 3 controls) using RT-qPCR.

Results: A total of 366 DEGs were identified in the diseased and normal groups. Among these, eight hub genes (TYROBP, CSF1R, CD163, ITGAM, CD86, FCGR3B, ITGB2, and IL10RA) showed strong correlations with immune cell content. These genes were predominantly enriched in pathways related to amino acid metabolism, viral protein interactions with cytokines and cytokine receptors, phagosome, chemokine signaling, programmed cell death, NF-κB, and other pathways. Additionally, these hub genes were linked to 39 regulatory factors. mRNA levels of these hub genes were validated in clinical samples through RT-qPCR. It is noteworthy that eight genes were found to be upregulated in GD samples.

Conclusion: The study highlights the potential impact of ITGB 2, TYROBP, CSF1R, CD163, ITGAM, CD86, FCGR3B, and IL10RA on the development and progression of GD, supporting their role as potential biomarkers.

Introduction: Stiff-person syndrome (SPS) is a rare neurological disorder that causes progressive muscle rigidity, gait disturbances, and functional impairment; type 1 is autoimmune, with positive anti-GAD antibodies (Ab), while type 2 is paraneoplastic and associated with antiamphiphysin Ab.

Case presentation: A 41-year-old man with a silent medical history presented with stiffness and functional impairment; after numerous rheumatological and neurological investigations, he was diagnosed with SPS, with evidence of high titer anti-GAD Ab. After treatment with benzodiazepines was started, the patient began to experience episodes of confusion, which persisted even after reducing the dosage. During one of these episodes, he was admitted to the emergency department and a glucose level of 26 mg/dL was found. Differential diagnosis led to detection of an insulin-secreting neuroendocrine tumor of the pancreas; thus, a paraneoplastic origin of SPS was hypothesized. However, antiamphiphysin Ab were negative, anti-GAD Ab were persistently elevated, and symptoms only transiently improved after removal of the tumor.

Conclusion: This is the first case, to our knowledge, demonstrating association between type 1 SPS and insulinoma, along with describing partial and transient improvement of neurological symptoms after resolution of the associated hypoglycemic syndrome.

Purpose: Hypoparathyroidism (HypoPT) is one of the most common complications of surgical treatment for thyroid cancer and afflicated patients often report symptoms or impairments in quality of life (QoL). We aimed to investigate differences in various QoL domains between thyroid cancer survivors with and without permanent hypoparathyroidism.

Methods: Thyroid cancer survivors with a minimum of 1.5 years post-diagnosis completed the EORTC core questionnaire (EORTC QLQ-C30) and the EORTC thyroid module (QLQ-THY34). Sociodemographic and clinical information were obtained from the patients themselves and their medical charts. Analysis of covariance was used to compare QoL between survivors with and without hypoparathyroidism (adjusting for age, gender, time since diagnosis, and comorbidity).

Results: Of the 126 participants, 21 (17%) were diagnosed with permanent HypoPT. There was no evidence of differences regarding any QoL domain between survivors due to hypoparathyroidism. The symptoms with the highest burden for both groups were fatigue (hypoPT: 24.9; non-hypoPT: 32.8; p = 0.151) and insomnia (hypoPT: 22.2; non-hypoPT: 30.8; p = 0.213). Thyroid cancer specific impairments were observed for joint pain (hypoPT: 28.6; non-hypoPT: 34.0; p = 0.480), worry about important others (hypoPT: 25.8; non-hypoPT: 27.9; p = 0.765), exhaustion (hypoPT: 23.8; non-hypoPT: 27.9; p = 0.482), and lacking social support (hypoPT: 36.5; no-hypoPT: 23.0; p = 0.070).

Conclusion: The present study appears to show that QoL in thyroid cancer survivors may be unrelated to hypoparathyroidism, further suggesting a more complex relationship between these two aspects.

Purpose: Women with gestational diabetes mellitus (GDM) are frequently asked to check their ketone levels by measuring ketonuria before breakfast. However, ketosis could be present even before lunch and dinner. Furthermore, blood ketone measurement could be a more accurate test. Our aim was to evaluate the effect of a blood ketone intensive measurement in the detection of ketosis in women with GDM with a negative urinary ketone test.

Methods: This was a single center, observational, prospective study involving consecutive women with GDM. Only women with negative fasting urinary ketone tests were included. During the same gestational weeks (weeks 30-32), all women were asked to perform a blood ketone test before their main meals. Ketosis was defined as the presence for at least 25% of the time of fasting blood ketone levels > 0.1 mmol/L and > 0.2 mmol/L before lunch and dinner.

Results: Overall, a total of 101 women (mean age 34.7 ± 4.8 years, prepregnancy BMI 28.2 ± 5.2 kg/m²) were studied. Blood ketones were present in 37.6% of the cases before breakfast, 13.9% before lunch, and 11.9% before dinner. Women with at least one daily presence of blood ketones composed 40.6% of the sample. Presence of fasting blood ketones was correlated with ketone presence before lunch (r = 0.63, p < 0.0001) and before dinner (r = 0.55, p < 0.0001) and with mean glucose levels (r = 0.23, p = 0.02) 1 h after breakfast.

Conclusion: Blood ketone testing in women with GDM can detect a larger number of ketosis episodes than a urinary ketone test. Intensive blood ketone measurement should be recommended to women with GDM.

Introduction: Obesity has been linked to an elevated susceptibility to development of erectile dysfunction, yet the interplay between sex hormone levels, sexual function, and obesity remains unclear. This study aimed to investigate sexual dysfunction among male patients with obesity and to emphasize the importance of recognizing the problem and pursuing solutions.

Methods: A total of 60 patients were included in the study (30 patients from the obesity center and 30 patients without obesity as the control group). Assessment of androgen hormone deficiency and erectile dysfunction was conducted through the implementation of AMS and IIEF-5 tests. The questionnaire includes aspects of medical history, demographic features, and lifestyle factors. Comprehensive measurements included BMI, WC, BP, lipid panel, total/free testosterone, sex-hormone-binding-globulin (SHBG), dehydroepiandrosterone-sulfate (DHEAS), fasting blood glucose (FBG), fasting insulin, and HbA1C levels. Results were evaluated using SPSS.

Results: The AMS score in the obesity group was significantly lower compared to the group without obesity. The IIEF-5 score did not exhibit a statistically significant difference between the groups. Testosterone, free testosterone, SHBG, and HDL values were lower in the obesity group compared to the group without obesity.

Conclusion: Although conducted in a small sample, our findings strongly indicate a positive correlation between obesity and the risk of moderate to severe ED. Most of the time, this condition goes unarticulated, thereby adversely affecting the quality of life for individuals with obesity. Clinicians should pay more attention to patients experiencing sexual dysfunction, especially those with obesity.

Purpose: This study aims to explore the inverse correlation between obesity and testosterone concentrations in men, with a particular focus on the role of hemodilution in this association. The research question addressed is whether hemodilution, due to increased plasma volume (PV), contributes to the lower testosterone concentrations observed in obese men.

Methods: We conducted a retrospective analysis using three datasets with sample sizes of 86, 134, and 446 participants, respectively. Multivariable linear regression models were used to examine the changes in PV, testosterone concentration, and mass across BMI categories, adjusting for age in each dataset and in the pooled data.

Results: The study demonstrated a significant inverse correlation between BMI groups and testosterone concentrations across the three datasets, as well as in the pooled data (beta coefficients: -0.024, -0.045, -0.040, -0.043; P < 0.001). Despite this, total testosterone mass remained stable (P > 0.05), suggesting that hemodilution, rather than a reduction in testosterone production, may account for the lower testosterone concentrations in obesity. Adjusted testosterone concentrations for obese participants were calculated using a formula that accounts for the increased PV.

Conclusion: Our findings suggest that hemodilution, associated with increased PV in obesity, is a significant factor contributing to the lower testosterone concentrations in obese men. This has implications for the diagnosis and treatment of testosterone deficiency in obesity and underscores the need for adjusted reference ranges. Further research is necessary to validate these findings and to explore their clinical implications.

Type 1 diabetes (T1D) is an autoimmune condition affecting approximately 1.5 million children and adolescents worldwide, with an incidence of approximately 2-3% each year and rising. During the recent COVID-19 pandemic, a significant increase in incidence of T1D in children and adolescents was observed in numerous countries worldwide, with an increased number of newly-diagnosed cases presenting with diabetic ketoacidosis. The increased frequency of T1D presenting with diabetic ketoacidosis has been attributed not only to the SARS-CoV-2 virus itself but also to the restrictions imposed by the pandemic. The shift to telemedicine and unwillingness to seek medical care due to fear of infection contributed to delayed diagnosis and more severe disease presentation. Furthermore, the periods of lockdown that were implemented during the pandemic presented multiple challenges for children and adolescents living with T1D and disrupted the management of their condition. Changes in physical activity and diet as well as shortage of medical supplies during that period have been linked to worsening of glycemic control, which were at least partly offset by increased parental involvement and use of telemedicine.

Objectives: To evaluate bone marrow fat concentration changes after sleeve gastrectomy in metabolic syndrome patients with and without diabetes.

Methods: A total of 58 metabolic syndrome patients (29 metabolic syndrome patients with diabetes (35.10 years ± 6.62) and 29 metabolic syndrome patients without diabetes (35.07 years ± 6.47)) who underwent sleeve gastrectomy received prospective follow-up for 2 years. Echo asymmetry, least square estimation-MRI, and laboratory tests were performed on all patients before and 2 years after surgery. The differences between baseline and end-of-study parameters were analyzed with the paired Student's t test. In addition, the associations of vertebral bone marrow fat concentration (denoted by proton density fat fraction, PDFF) with other variables were determined using multiple linear regression analysis.

Results: Bone proton density fat fraction decreased significantly among patients with diabetes (from 38.62 ± 8.01 to 34.54 ± 7.54, P = 0.003) and without diabetes (from 36.82 ± 8.80 to 35.09 ± 8.33, P = 0.011) after sleeve gastrectomy. Among patients with diabetes, multivariable predictors of changes in proton density fat fraction by descending order of standardized coefficient were changes in HbA1c (2.690, P < 0.001), baseline HbA1c (2.354, P < 0.001), changes in insulin (0.627, P < 0.001), changes in low-density lipoprotein cholesterol (0.597, P = 0.013), and changes in C-peptide (-0.664, P = 0.001). Among patients without diabetes, multivariable predictors of changes in proton density fat fraction were changes in low-density lipoprotein cholesterol (1.486, P < 0.001), changes in high-density lipoprotein cholesterol (0.460, P = 0.003), baseline low-density lipoprotein cholesterol (0.438, P = 0.014), changes in triglyceride (0.383, P = 0.007), and changes in total cholesterol (-1.614, P < 0.001).

Conclusions: Sleeve gastrectomy may decrease bone marrow fat concentration of MetS patients regardless of diabetes status. Changes in bone marrow fat concentration may be influenced by different factors based on diabetes status.