Endocrine Research最新文献

Background: Obesity in youth is associated with increased risk of metabolic disorders. Adipose tissue hormones are involved in body-weight regulation. Among these, apelin is recognized as an insulin-sensitizer adipokine. Data on apelin levels in obese children and its relation to insulin-sensitivity are limited.

Objective: We aimed to evaluate apelin levels in relation to obesity and insulin sensitivity in a large cohort of overweight/obese children and adolescents. Furthermore, these youths were reevaluated after a median 6.5 years of follow-up, thus allowing assessing changes in apelin levels in relation to increasing age and weight changes.

Methods: Clinical data in 909 children and adolescents were collected between 2007 and 2010. Two hundred and one were reexamined at a median 6.5 years of follow-up. All subjects at baseline and at follow-up underwent an OGTT. Apelin levels were measured on sera by ELISA method.

Results: At baseline, lower apelin levels were associated with increasing age and puberty (Tanner ≥II 0.67 ± 0.96 ng/mL vs. Tanner I 0.89 ± 1.13 ng/mL, p < .002), but not with body-weight. At follow-up, apelin levels in the 201 subjects reexamined were significantly lower than at baseline (0.45 ± 0.77 ng/mL at follow-up, 0.68 ± 0.95 ng/mL baseline, p < .001), confirming the effects of age and puberty. Body-weight did not affect apelin levels. Multiple regression analysis confirmed that sex and puberty were associated with lower apelin levels, independently from age and insulin-sensitivity.

Conclusions: Apelin levels decrease significantly with pubertal development, whilst body-weight in children and adolescents did not determine changes in apelin. Reduced levels of apelin in children and adolescents may therefore represent a necessary response to maintain the "physiological" insulin resistance of puberty. Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; G: glucose; BMI: Body mass index; DBP: Diastolic blood pressure; ELISA: enzyme-linked immunosorbent assay; HDL-C: High-density lipoprotein-cholesterol; HOMA-B: Homeostatic model assessment for beta-cell function; HOMA-IR: Homeostatic model assessment of insulin-resistance; INS: Insulin; ISI: insulin-sensitivity index; LDL-C: Low-density lipoprotein cholesterol; NW: normal weight; OB: obese; OGTT: oral glucose tolerance test; OW: overweight; SBP: Systolic blood pressure; TC: Total cholesterol; TGs: Triglycerides.

Background: Gender transitioning is increasingly common, but little is known about the extent to which individuals in transition and fully transitioned suffer from wage discrimination. Methods: Managers in the United States (n=204) were shown photos of white and Asian male and female "employees" at different stages of simulated hormone therapy and were asked to estimate their actual hourly wages based on appearance.

Results: The results suggest that Asian men and women "in transition" and fully transitioned do not suffer from significant wage discrimination. However, among the white stimuli, gender atypical ("in transition" and fully transitioned) men and women are estimated to earn significantly less than their gender typical (sexually dimorphic) counterparts, with some gender-specific nuances.

Conclusions: The effects of hormone therapy may have a deleterious impact on the wages of white transgender individuals.

Aims: Metabolic Syndrome (MetS) a global problem, which comprises a cardio-metabolic cluster of risk factors, increases the risk for type-2 diabetes (T2DM) and atherosclerotic cardiovascular diseases (ASCVD). To date, the best laboratory-based biomarker for MetS appears to be high-sensitivity C-reactive protein (hsCRP). Chemerin, a novel adipokine is increased in MetS and appears to contribute to both insulin resistance and inflammation. In this pilot study, we tested if the chemerin:HDL-C or chemerin:adiponectin ratios are better biomarkers for predicting MetS than hsCRP.

Patients and methods: We enrolled patients and controls with nascent MetS, uncomplicated by diabetes, ASCVD, macro-inflammation, and smoking using rigorous criteria. Fasting blood samples were obtained in order to calculate insulin resistance in the liver (HOMA-IR) and adipose tissue (ADIPO-IR) and for measurement of chemerin and adiponectin levels. Statistical analyses including receiver operating characteristic (ROC) curves were used to evaluate data.

Results: We observed the chemerin:HDL-C ratio is significantly increased in MetS and increases with severity of MetS (p < .001). The chemerin: adiponectin ratio was not significantly increased following adjustment for age and waist circumference. The chemerin:HDL-C ratio correlated with BMI, WC, triglycerides, plasma glucose, HDL-C, and both HOMA-IR and ADIPO-IR. ROC curve analysis showed that the chemerin:HDL-C ratio area under the curve (AUC) was greater than the AUC for hsCRP.

Conclusion: In this preliminary report, we demonstrate that the ratio of chemerin to HDL-C is a valid biomarker of MetS and appears to be a better predictor than hsCRP. These findings need to be confirmed in larger studies.

Purpose: To present a case series of primary and immunotherapy-related secondary hypophysitis.

Methods: A single-center retrospective chart review was performed at the University of British Columbia, Vancouver, Canada. Eleven cases of primary hypophysitis and 2 cases of immunotherapy-related secondary hypophysitis were included. Of the 11 primary cases, 6 were diagnosed clinically without biopsy.

Results: In primary hypophysitis, headache was the most common presenting symptom (6/11; 55%) and stalk enlargement the prevailing radiologic sign (8/11; 73%). Central adrenal insufficiency (4/11; 36%), central hypothyroidism (4/11; 36%), and central diabetes insipidus (CDI) (4/11; 36%) were the most common pituitary deficiencies at presentation. Initial management included surgery (4/11; 36%), supraphysiologic steroids (2/11; 18%), or observation (6/11; 55%). Outcomes assessed included radiologic improvement (8/9; 89%), improvement in mass symptoms (4/7; 57%), anterior pituitary recovery (1/7; 14%), and CDI recovery (0/4; 0%). In immunotherapy-related hypophysitis either under observation or supraphysiologic steroid therapy, the inflammatory mass resolved and pituitary dysfunction persisted.

Conclusions: In primary hypophysitis, the inflammatory pituitary mass typically resolves and hypopituitarism persists. In the absence of severe or progressive neurologic deficits, a presumptive clinical diagnosis and conservative medical management should be attempted. In the absence of severe features, immunotherapy-related hypophysitis may be managed effectively without the use of supraphysiologic steroids.

Purpose: To observe the expression of Nrg4, uncoupling protein-1 (UCP1), tumor necrosis factor α (TNFα), CD31, VE-cadherin/CDH5 and vascular endothelial growth factor A (VEGF-A) mRNA in abdominal subcutaneous (SC), omental (OM) adipose tissue in children with relation to anthropometric parameters. Further to verify the effect of inflammatory mediators on Nrg4 and UCP1 mRNA expression in adipocytes.

Methods: Paired SC and OM adipose tissues were obtained from 58 children. In vitro, the adipocytes isolated from primary inguinal adipose tissue of mice were treated with TNFα (50 ng/ml) for 12-48 h. mRNA levels of Nrg4, UCP1 and TNFα were determined by real-time PCR.

Results: Nrg4, UCP1, VEGF-A and CDH5 mRNA levels in SC were significantly higher than those in OM adipose tissue and the mRNA level of TNFα showed the opposite result. Moreover, Nrg4 and UCP1 mRNA in SC were significantly lower in overweight children compared to normal weight children. Nrg4 in SC and OM was negatively associated with BMISDS, WHtR. CDH55 mRNA in OM was negatively associated with WHR. VEGF-A was positively correlated with Nrg4 in SC. In vitro, Nrg4 and UCP1 mRNA levels in adipocytes were dose- and time-dependently decreased under TNFα treatment.

Conclusions: Nrg4, UCP1, VEGF-A and CDH5 mRNA expression in adipose tissues display a depot-specific pattern. Nrg4 mRNA levels in adipose tissue are decreased with obesity and associated with WAT browning and angiogenesis. TNFα may be involved in the regulation of Nrg4 level in adipose tissue, which may be one of the causes of the down-regulation of Nrg4 expression in obesity with chronic inflammatory response.

Purpose: The association between obesity and autoimmune diseases has been suggested by several previous studies. The objective of our study was to assess the association of abdominal obesity phenotypes with thyroid autoimmunity.

Materials and methods: This study was conducted within the framework of a population-based cohort study, Tehran Thyroid Study (TTS) on 4708 subjects without thyroid autoimmunity at baseline. Participants were categorized into four abdominal obesity phenotypes according to waist circumference (WC) and other metabolic syndrome components. Serum concentrations of thyroid peroxidase antibody (TPOAb), free T4 (FT4), thyrotropin (TSH), glucose, and lipid profiles were measured after 3, 6 and 9 years of follow-up. Cox proportional hazard models were used to evaluate associations of different phenotypes with the incidence of thyroid autoimmunity, adjusted for age, sex, FT4, and TSH.

Results: Highest and lowest incidence rates of TPOAb positivity were observed among metabolically unhealthy, non-abdominally obese (MUNAO) [8.78 (7.31-10.55) per 1000 person-years of follow-up] and metabolically unhealthy abdominally obese (MUAO) [4.98 (3.88-6.41) per 1000 person-years of follow-up] phenotypes. Considering the metabolically healthy non-abdominal obese (MHNAO) individuals as reference, none of metabolically healthy abdominally obese (MHAO), MUNAO, and MUAO phenotypes were associated with increased risk of developing TPOAb positivity. Compared to individuals with high WC, the incidence rate (95%CI) of TPOAb positivity was higher among those with normal WC: 8.44 (7.13-10.0) vs 5.11 (4.01-6.51) per 1000 person-years, respectively. Higher WC was not associated with incident TPOAb positivity.

Conclusion: There was no significant association between baseline abdominal obesity phenotype status and development of TPOAb positivity over 9 years of follow-up.

Purpose/aims: The relationship between thyroid-stimulating hormone (TSH) and lipoprotein subfractions by Vertical Auto Profile (VAP) is unclear. We aimed to evaluate lipoprotein profiles according to TSH levels in euthyroid individuals.Material and Methods: Cross-sectional analysis of 3,525 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) with no previous thyroid disease and who were not on lipid-lowering medication. Total-cholesterol and its fractions, lipoprotein subfractions, triglycerides, and triglyceride-rich lipoprotein cholesterol [TRL-C (VLDL₁₊₂-C, VLDL₃-C, IDL-C)] were determined by VAP. Associations between TSH quintiles and lipoprotein subfractions were evaluated by crude and adjusted linear regression models.Results: For the total sample, significant beta-coefficients in full adjusted models for the 5^th quintile of TSH (compared to 1^st) were found for the following VAP lipids and lipoproteins: IDL-C (β: 0.90; 0.11 to 1.69); VLDL-C (β: 2.80; 1.51 to 4.08), triglycerides (β: 18.66; 8.07 to 29.25), non-HDL-C (β: 4.63; 0.50 to 8.75 mg/dl), TRL-C (β:1.93;0.70 to 3.17), VLDL₃-C (β: 1.04; 0.50 to 1.57), as well as, TC/HDL-C (β: 0.15; 0.03 to 0.26) and TG/HDL-C ratio (β: 0.49;0.21 to 0.77). In women, similar results were found for VLDL-C, triglycerides, non-HDL-C, TRL-C, VLDL₃-C, TC/HDL-C and TG/HDL-C-ratios. In men, we also found positive associations between the highest quintile of TSH with VLDL-C, triglycerides, VLDL₃-C and TG/HDL-C.Conclusions: In the ELSA-Brasil, the highest TSH levels were mostly positively associated with lipoprotein levels, particularly TG, TRL and their remnants. Notwithstanding, our findings suggest that TSH levels within the normal range have little impact on the atherogenic profile.

Background: Uptake of coronaviruses by target cells involves binding of the virus by cell ectoenzymes. For the etiologic agent of COVID-19 (SARS-CoV-2), a receptor has been identified as angiotensin-converting enzyme-2 (ACE2). Recently it has been suggested that plasma membrane integrins may be involved in the internalization and replication of clinically important coronaviruses. For example, integrin αvβ3 is involved in the cell uptake of a model porcine enteric α-coronavirus that causes human epidemics. ACE2 modulates the intracellular signaling generated by integrins.

Objective: We propose that the cellular internalization of αvβ3 applies to uptake of coronaviruses bound to the integrin, and we evaluate the possibility that clinical host T4 may contribute to target cell uptake of coronavirus and to the consequence of cell uptake of the virus.

Discussion and conclusions: The viral binding domain of the integrin is near the Arg-Gly-Asp (RGD) peptide-binding site and RGD molecules can affect virus binding. In this same locale on integrin αvβ3 is the receptor for thyroid hormone analogues, particularly, L-thyroxine (T4). By binding to the integrin, T4 has been shown to modulate the affinity of the integrin for other proteins, to control internalization of αvβ3 and to regulate the expression of a panel of cytokine genes, some of which are components of the 'cytokine storm' of viral infections. If T4 does influence coronavirus uptake by target cells, other thyroid hormone analogues, such as deaminated T4 and deaminated 3,5,3'-triiodo-L-thyronine (T3), are candidate agents to block the virus-relevant actions of T4 at integrin αvβ3 and possibly restrict virus uptake.

Background and aim: While the relationship between obesity and reproductive dysfunction is well known, the physiological mechanism behind obesity-related infertility remains unclear. Previous work suggests that follicle development prior to ovulation is disrupted in obese individuals. Follicle-stimulating hormone (FSH) and anti-Mullerian hormone (AMH) are two key regulators of follicle development, and the poorest reproductive outcomes have been recorded when these hormones are imbalanced. In order to understand how obesity impacts the reproductive axis, the present study induces reproductive dysfunction in female rats using a high-fat, high-sugar diet (HFHS). Results: In our study, several animals on the HFHS diet displayed abnormal estrous cycles. The HFHS diet also resulted in an increased prevalence of ovarian cysts and decreased formation of corpora lutea. Across all groups, the FSH/AMH ratio displayed a strong negative correlation with pre-antral, antral, and total follicle counts. Moreover, rats on the HFHS diet displayed larger adipocytes and produced higher levels of leptin than controls. When combined with average adipocyte size in multiple regression, the FSH/AMH ratio was strongly associated with cyst formation in the ovary. Conclusions: These findings provide strong evidence for the potential relevance of a combined FSH/AMH ratio as a marker of ovarian health and follicular status. Therefore, this ratio reflects a complex interaction between the reproductive and metabolic systems.