Circulating Adiponectin Levels Research Articles

Association of circulating adiponectin levels with the incidence of ischemic stroke: a meta-analysis

Association of circulating adiponectin levels with the incidence of ischemic stroke: a meta-analysis

The role of adiponectin in the association between abdominal obesity and type 2 diabetes: a mediation analysis among 232,438 Chinese participants.

Adiposity and adipokines are closely associated with obesity-related metabolic abnormalities, but little is known regarding whether abdominal obesity is linked to type 2 diabetes mellitus (T2DM) through circulating adiponectin levels. Thus, this large-population-based study was designed to investigate the mediating effect of adiponectin in the relationship between abdominal obesity and T2DM. A total of 232,438 adults who lived in Dongguan, Guangdong Province, China, were enrolled in the present study. The circulating adiponectin concentrations were measured using latex-enhanced immunoturbidimetric assay. The association between circulating adiponectin and other clinical parameters was detected by Spearman's correlation analysis. Restricted cubic spline (RCS) regression was also used to address the non-linearity of the relationship between waist circumference and diabetes. Mediation analyses of circulating adiponectin were conducted using linear and logistic regression. Subjects with abdominal obesity had lower levels of circulating adiponectin (P < 0.001). The circulating adiponectin value was inversely related to BMI (r = -0.370, P < 0.001), waist circumference (r = -0.361, P < 0.001), and fasting plasma glucose (r = -0.221, P < 0.001). The RCS plot showed a non-linear relation linking waist circumference with T2DM (P for non-linearity < 0.001). Patients with abdominal obesity presented 2.062 times higher odds of T2DM in comparison with those with non-abdominal obesity (odds ratio, 2.062; 95% confidence interval, 1.969-2.161) after adjusting for confounders. In the mediation analyses, the circulating adiponectin mediated the association between abdominal obesity and T2DM, with a mediation effect of 41.02% after adjustments. The above results were consistent in both men and women. The relationship between abdominal obesity and T2DM is mediated through circulating adiponectin level in adults, suggesting that circulating adiponectin might be a potential predictor for controlling the adverse progression from adiposity to T2DM.

Relationship between adiponectin and muscle mass in patients with metabolic syndrome and obesity

BackgroundAdiponectin is one of the most important adipokines in human beings. Obesity and sarcopenia are associated with a low-level chronic inflammatory status, and adiponectin plays an anti-inflammatory role. AimsThe objective of the current work was to study the association between muscle mass, determined via bioelectrical impedance (BIA), and circulating adiponectin levels among obese patients with metabolic syndrome who are older than 60 years of age. MethodsWe performed a cross-sectional study incorporating 651 patients with obesity and metabolic syndrome. Anthropometric data, BIA data (total fat mass (FM), fat-free mass (FFM), fat-free mass index (FFMi), skeletal muscle mass (SMM) and skeletal muscle mass index (SMMi)), arterial pressure, HOMA-IR (homeostasis model assessment of insulin resistance), and biochemical parameters were recorded. ResultsThe patients were separated into two groups based on their median SMMi (skeletal muscle mass index) levels. The low-SMMi group presented adiponectin levels that were higher than those in the high-SMMi group (delta value: 4.8 + 0.7 ng/dl: p = 0.02). Serum adiponectin values were negatively correlated with fat mass (FM), fat-free mass (FFM), fat-free mass index (FFMi), SMM, and SMMi. Adiponectin presented a negative correlation with HOMA-IR and a positive correlation with HDL-cholesterol. In the final multivariate model using SMMi as a dependent variable, adiponectin levels explained 18 % of the variability (Beta −0.49, CI95% −0.89 to −0.16) after adjusting for age and gender. ConclusionsSerum adiponectin levels are negatively associated with low skeletal muscle mass among obese subjects with metabolic syndrome who are older than 60 years of age.

Depleting inositol pyrophosphate 5-InsP7 protected the heart against ischemia-reperfusion injury by elevating plasma adiponectin.

Adiponectin is an adipocyte-derived circulating protein that exerts cardiovascular and metabolic protection. Due to the futile degradation of endogenous adiponectin and the challenges of exogenous administration, regulatory mechanisms of adiponectin biosynthesis are of significant pharmacological interest. Here, we report that 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) generated by inositol hexakisphosphate kinase 1 (IP6K1) governed circulating adiponectin levels via thiol-mediated protein quality control in the secretory pathway. IP6K1 bound to adiponectin and DsbA-L and generated 5-InsP7 to stabilize adiponectin/ERp44 and DsbA-L/Ero1-Lα interactions, driving adiponectin intracellular degradation. Depleting 5-InsP7 by either IP6K1 deletion or pharmacological inhibition blocked intracellular adiponectin degradation. Whole-body and adipocyte-specific deletion of IP6K1 boosted plasma adiponectin levels, especially its high molecular weight forms, and activated AMPK-mediated protection against myocardial ischemia-reperfusion injury. Pharmacological inhibition of 5-InsP7 biosynthesis in WT but not adiponectin knockout mice attenuated myocardial ischemia-reperfusion injury. Our findings revealed that 5-InsP7 is a physiological regulator of adiponectin biosynthesis that is amenable to pharmacological intervention for cardioprotection.

Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse model

Polycystic ovary syndrome (PCOS) is associated with symptoms of moderate to severe anxiety and depression. Hyperandrogenism is a key feature together with lower levels of the adipocyte hormone adiponectin. Androgen exposure leads to anxiety-like behavior in female offspring while adiponectin is reported to be anxiolytic. Here we test the hypothesis that elevated adiponectin levels protect against the development of androgen-induced anxiety-like behavior. Pregnant mice overexpressing adiponectin (APNtg) and wildtypes were injected with vehicle or dihydrotestosterone to induce prenatal androgenization (PNA) in the offspring. Metabolic profiling and behavioral tests were performed in 4-month-old female offspring. PNA offspring spent more time in the closed arms of the elevated plus maze, indicating anxiety-like behavior. Intriguingly, neither maternal nor offspring adiponectin overexpression prevented an anxiety-like behavior in PNA-exposed offspring. However, adiponectin overexpression in dams had metabolic imprinting effects, shown as lower fat mass and glucose levels in their offspring. While serum adiponectin levels were elevated in APNtg mice, cerebrospinal fluid levels were similar between genotypes. Adiponectin overexpression improved metabolic functions but did not elicit anxiolytic effects in PNA-exposed offspring. These observations might be attributed to increased circulating but unchanged cerebrospinal fluid adiponectin levels in APNtg mice. Thus, increased adiponectin levels in the brain are likely needed to stimulate anxiolytic effects.

Therapeutic potential of adiponectin in prediabetes: strategies, challenges, and future directions.

Adiponectin, an adipose-derived hormone, plays a pivotal role in glucose regulation and lipid metabolism, with a decrease in circulating adiponectin levels being linked to insulin resistance and prediabetes. This review examines the therapeutic potential of adiponectin in managing prediabetes, elucidating on multiple aspects including its role in glucose and lipid metabolism, influence on insulin sensitivity, and anti-inflammatory properties. Moreover, the paper highlights the latest strategies to augment adiponectin levels, such as gene therapy, pharmacological interventions, dietary modifications, and lifestyle changes. It also addresses the challenges encountered in translating preclinical findings into clinical practice, primarily related to drug delivery, safety, and efficacy. Lastly, the review proposes future directions, underlining the need for large-scale human trials, novel adiponectin analogs, and personalized treatment strategies to harness adiponectin's full therapeutic potential in preventing the transition from prediabetes to diabetes.

Exploring the Relationship between Plasma Adiponectin, Gender, and Underlying Diseases in Severe Illness.

Adiponectin is low in obesity, plays a crucial role in metabolic health, and, moreover, possesses immunoregulatory properties. However, studies examining its levels in patients with systemic inflammatory response syndrome (SIRS) or sepsis have yielded conflicting results. While females typically have higher systemic adiponectin levels than males, research on sex-specific associations in this context is limited. In this study of 156 SIRS/sepsis patients, including those with liver cirrhosis, we aimed to explore the relationship between plasma adiponectin, body mass index (BMI), gender, disease severity, and underlying etiological conditions. Our findings revealed that patients with liver cirrhosis, who are susceptible to infections, exhibited elevated circulating adiponectin levels, irrespective of sex. When excluding cirrhosis patients, plasma adiponectin levels were similar between male SIRS/sepsis patients and controls but lower in female patients compared to female controls. Plasma adiponectin was inversely related to BMI in female but not male patients. Further analysis within the non-cirrhosis subgroup demonstrated no significant differences in adiponectin levels between sexes among SIRS, sepsis, and septic shock patients. Ventilation, dialysis, and vasopressor therapy had no discernible impact on adiponectin levels in either sex. A negative correlation between adiponectin and C-reactive protein (CRP) existed in males only. Notably, patients with pancreatitis showed the lowest plasma adiponectin concentrations, although sex-specific differences were not significant. Infection with Gram-negative or Gram-positive bacteria had minimal effects on plasma adiponectin levels in both sexes. However, infection with the severe acute respiratory syndrome coronavirus type 2 led to decreased adiponectin levels in females exclusively. Multivariate analysis considering all factors affecting plasma adiponectin levels in males or females identified BMI in females and CRP levels in males to predict plasma adiponectin levels in SIRS/sepsis patients. Additionally, our study observed a trend where the 25 patients who did not survive had higher plasma adiponectin levels, particularly among males. In summary, our investigation highlights the influence of underlying diseases and sex on plasma adiponectin levels in SIRS/sepsis patients, shedding light on potential implications for disease management and prognosis.

Adiponectin serum levels and ADIPOQ (rs2241766) polymorphism in alopecia areata Egyptian patients

BackgroundAlopecia Areata (AA) is an acquired autoimmune form of non-scarring hair loss. Adiponectin and its gene polymorphism were related to many autoimmune disorders. ObjectiveAssessment of adiponectin serum levels and adiponectin gene (ADIPOQ) (rs2241766) Single Nucleoid Polymorphism (SNP) in AA patients and correlating the results with the disease severity in those patients. MethodsThis study included 75 AA patients and 75 age and gender-matched healthy subjects (controls). The severity of Alopecia Tool (SALT) score assessment to evaluate AA severity was done. Adiponectin serum levels by ELISA and ADIPOQ (rs2241766) SNP using PCR were performed. ResultsAdiponectin serum levels were significantly lower in AA patients than controls (p = 0.001). ADIPOQ (rs2241766) TG genotype and G allele were significantly predominant in AA patients increasing its risk by 5 and 4 folds (OR = 5.17, p = 0.001), (OR = 3.82, p = 0.001) respectively. Serum adiponectin levels were negatively correlated with SALT score (r = -0.435, p = 0.001) and associated with alopecia totalis (p = 0.016). ADIPOQ (rs2241766) TG genotype was significantly associated with low serum adiponectin levels and higher SALT score (p = 0.001). Study limitationsThe small sample size. ConclusionsADIPOQ (rs2241766) gene polymorphism (TG genotype and G allele) may modulate AA risk and contribute to the development of AA in Egyptian populations. Decreased circulating adiponectin levels may have a dynamic role in AA etiopathogenesis. Adiponectin serum concentration can be considered a severity marker of hair loss in AA.

Genetic Association of Circulating Adipokines with Risk of Idiopathic Pulmonary Fibrosis: A Two-Sample Mendelian Randomization Study.

The causal relationships between circulating adipokines and idiopathic pulmonary fibrosis (IPF) are yet to be established. We performed a two-sample Mendelian randomization (MR) study to investigate the causal roles of adipokines on IPF risk. We analyzed the summary data from genome-wide association studies (GWAS), including adiponectin, leptin, resistin and monocyte chemoattractant protein-1 (MCP-1) and IPF. The inverse-variance weighted (IVW) method was considered as the major method and the MR-Egger, weighted median, simple mode and weighted mode were utilized as complementary methods. We also performed the sensitivity analyses, including heterogeneity test, horizontal pleiotropy test and leave-one-out analysis. The selected number of single nucleotide polymorphisms (SNPs) was 13 for adiponectin, 6 for leptin,12 for resistin, and 6 for MCP-1, respectively. The results showed a causal effect of the circulating adiponectin levels on the risk of IPF (OR 0.645, 95% CI 0.457-0.911, P = 0.013). However, we did not observe significant associations of genetic changes in serum leptin (OR 1.018, 95% CI 0.442-2.346, P = 0.967), resistin (OR 1.002, 95% CI 0.712-1.408, P = 0.993), and MCP-1 (OR 1.358, 95% CI 0.891-2.068, P = 0.155) with risk of developing IPF. There was no evidence of heterogeneity or horizontal pleiotropy. The sensitivity analyses confirmed that our results were stable and reliable. The increase in serum adiponectin was associated causally with a decreased risk of developing IPF. There is no evidence to support a causal association between leptin, resistin or MCP-1 with risk of IPF. Further studies are needed to confirm our findings.

Biochanin-A attenuates DHEA-induced polycystic ovary syndrome via upregulation of GDF9 and BMP15 signaling in vivo

AimsPhytoestrogens can act as natural estrogens owing to their structural similarity to human estrogens. Biochanin-A (BCA) is a well-studied phytoestrogen with a wide variety of pharmacological activities, whereas not reported in the most frequently encountered endocrinopathy called polycystic ovary syndrome (PCOS) in women. PurposeThis study aimed to investigate the therapeutic effect of BCA on dehydroepiandrosterone (DHEA) induced PCOS in mice. Main methodsThirty-six female C57BL6/J mice were divided into six groups: sesame oil, DHEA-induced PCOS, DHEA + BCA (10 mg/kg/day), DHEA + BCA (20 mg/kg/day), DHEA + BCA (40 mg/kg/day), and metformin (50 mg/kg/day). Key findingsThe results showed a decrease in obesity, elevated lipid parameters, restoration of hormonal imbalances (testosterone, progesterone, estradiol, adiponectin, insulin, luteinizing hormone, and follicle-stimulating hormone), estrus irregular cyclicity, and pathological changes in the ovary, fat pad, and liver. SignificanceIn conclusion, BCA supplementation inhibited the over secretion of inflammatory cytokines (TNF-α, IL-6, and IL-1β) and upregulated TGFβ superfamily markers such as GDF9, BMP15, TGFβR1, and BMPR2 in the ovarian milieu of PCOS mice. Furthermore, BCA reversed insulin resistance by increasing circulating adiponectin levels through a negative correlation with insulin levels. Our results indicate that BCA attenuated DHEA-induced PCOS ovarian derangements, which could be mediated by the TGFβ superfamily signaling pathway via GDF9 and BMP15 and associated receptors as first evidenced in this study.

Association between circulating adiponectin levels and androgen excess in polycystic ovarian syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Circulating Adiponectin Levels Are Inversely Associated with Mortality and Respiratory Failure in Patients Hospitalized with COVID-19.

Chronic low-grade inflammation associated with a dysregulated adipose tissue might contribute to amplifying the inflammatory response in severe COVID-19. The aim of this study was to examine the association between levels of circulating leptin and adiponectin and the severity and mortality of COVID-19. Serum levels of leptin and adiponectin were determined at admission in 123 individuals with confirmed COVID-19 and their association with 90-day mortality and respiratory failure was analyzed by logistic regression analysis and expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The median values of circulating leptin and adiponectin were 7.2 ng/mL (IQR 3.8-13.4) and 9.0 μg/mL (IQR 5.7-14.6), respectively. After adjustment for age, sex, body mass index, hypertension, diabetes, chronic obstructive pulmonary disease, and oxygen saturation at admission, a doubling of circulating adiponectin was associated with a 38% reduction in odds of 90-day mortality (OR 0.62, CI 0.43-0.89) and a 40% reduction in odds of respiratory failure (OR 0.60, CI 0.42-0.86). The association tended to be strongest in individuals below the median age of 72 years. Circulating leptin was not associated with outcomes. Circulating adiponectin at admission was inversely associated with mortality and respiratory failure in SARS-CoV-2 infection. Further studies are needed to elucidate how exactly adipokines, especially adiponectin, are linked to the progression and prognosis of COVID-19.

Prenylated Chrysin Derivatives as Partial PPARγ Agonists with Adiponectin Secretion-Inducing Activity.

Decreased circulating adiponectin levels are associated with an increased risk of human metabolic diseases. The chemical-mediated upregulation of adiponectin biosynthesis has been proposed as a novel therapeutic approach to managing hypoadiponectinemia-associated diseases. In preliminary screening, the natural flavonoid chrysin (1) exhibited adiponectin secretion-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells (hBM-MSCs). Here, we provide the 7-prenylated chrysin derivatives, chrysin 5-benzyl-7-prenylether compound 10 and chrysin 5,7-diprenylether compound 11, with the improved pharmacological profile compared with chrysin (1). Nuclear receptor binding and ligand-induced coactivator recruitment assays revealed that compounds 10 and 11 functioned as peroxisome proliferator-activated receptor (PPAR)γ partial agonists. These findings were supported by molecular docking simulation, followed by experimental validation. Notably, compound 11 showed PPARγ binding affinity as potent as that of the PPARγ agonists pioglitazone and telmisartan. This study presents a novel PPARγ partial agonist pharmacophore and suggests that prenylated chrysin derivatives have therapeutic potential in various human diseases associated with hypoadiponectinemia.

Relationships of adiponectin to regional adiposity, insulin sensitivity, serum lipids, and inflammatory markers in sedentary and endurance-trained Japanese young women.

This study aims to compare the differences in circulating adiponectin levels and their relationships to regional adiposity, insulin resistance, serum lipid, and inflammatory factors in young, healthy Japanese women with different physical activity statuses. Adipokines (adiponectin and leptin), full serum lipid, and inflammatory factors [white blood cell counts, C-reactive protein, tumor necrosis factor-α, tissue plasminogen activator inhibitor-1 (PAI-1)] were measured in 101 sedentary and 100 endurance-trained healthy Japanese women (aged 18-23 years). Insulin sensitivity was obtained through a quantitative insulin-sensitivity check index (QUICKI). Regional adiposity [trunk fat mass (TFM), lower-body fat mass (LFM), and arm fat mass (AFM)] was evaluated using the dual-energy X-ray absorptiometry method. No significant difference was observed between the sedentary and trained women in terms of adiponectin levels. The LFM-to-TFM ratio and the high-density lipoprotein cholesterol (HDL-C) were the strong positive determinants for adiponectin in both groups. Triglyceride in the sedentary women was closely and negatively associated with adiponectin, as well as PAI-1 in the trained women. The QUICKI level was higher in the trained than sedentary women. However, no significant correlation between adiponectin and insulin sensitivity was detected in both groups. Furthermore, LFM was associated with a favorable lipid profile against cardiovascular diseases (CVDs) in the whole study cohort, but this association became insignificant when adiponectin was taken into account. These findings suggest that adiponectin is primarily associated with regional adiposity and HDL-C regardless of insulin sensitivity and physical activity status in young, healthy women. The associations among adiponectin, lipid, and inflammatory factors are likely different in women with different physical activity statuses. The correlation of LFM and a favorable lipid profile against CVD and adiponectin is likely involved in this association.

The Role of Adiponectin during Pregnancy and Gestational Diabetes.

Pregnancy involves a range of metabolic adaptations to supply adequate energy for fetal growth and development. Gestational diabetes (GDM) is defined as hyperglycemia with first onset during pregnancy. GDM is a recognized risk factor for both pregnancy complications and long-term maternal and offspring risk of cardiometabolic disease development. While pregnancy changes maternal metabolism, GDM can be viewed as a maladaptation by maternal systems to pregnancy, which may include mechanisms such as insufficient insulin secretion, dysregulated hepatic glucose output, mitochondrial dysfunction and lipotoxicity. Adiponectin is an adipose-tissue-derived adipokine that circulates in the body and regulates a diverse range of physiologic mechanisms including energy metabolism and insulin sensitivity. In pregnant women, circulating adiponectin levels decrease correspondingly with insulin sensitivity, and adiponectin levels are low in GDM. In this review, we summarize the current state of knowledge about metabolic adaptations to pregnancy and the role of adiponectin in these processes, with a focus on GDM. Recent studies from rodent model systems have clarified that adiponectin deficiency during pregnancy contributes to GDM development. The upregulation of adiponectin alleviates hyperglycemia in pregnant mice, although much remains to be understood for adiponectin to be utilized clinically for GDM.

CORRELATION BETWEEN INTAKE OF DIETARY PHYTOCHEMICALS AND CIRCULATING ADIPONECTIN LEVEL IN TYPE 2 DIABETIC NIGERIANS: AN OBSERVATIONAL STUDY

Background: Regular consumption of dietary phytochemicals as part of dietary pattern has been suggested as a possible effective dietary strategy of modulating circulating adiponectin level in patients with type 2 diabetes mellitus. However, findings from previous studies across different ethnic groups are inconsistent. Objective: The aim of this study was to determine the relationship between intake of dietary phytochemicals and circulating level of adiponectin among a group of patients with type 2 diabetes mellitus in a specialist hospital in north eastern Nigeria. Methods: Dietary intake assessment was done using a semi quantitative food frequency questionnaire and intake of dietary phytochemicals was calculated as dietary phytochemical index. The study subjects were categorized in to four quartiles according to their median intake of dietary phytochemicals. Fasting plasma glucose and adiponectin were measured among the study subjects. Analysis of variance and partial correlation analyses were used to determine the relationships between the study variables. Results: Higher circulating adiponectin level was observed among subjects with higher intake of dietary phytochemicals in the fourth quartile compared to the subjects with lower intake of dietary phytochemicals in the first quartile (9.8 ± 2.5µg/mL vs 8.2 ± 2.3µg/mL, p-value for trend &lt; 0.05).There was a statistically significant positive correlation between intake of dietary phytochemicals and plasma level of adiponectin, among the study subjects, regardless of gender and independent of age and BMI and duration of diabetes mellitus (r = 0.20, p &lt; 0.05). Conclusion: We conclude that among subjects with type 2 diabetes mellitus in this study, consumption of a diet rich in phytochemicals has the potential to improve circulating adiponectin level. We recommend further interventional studies to establish the role of dietary phytochemicals in the optimization of the management of type 2 diabetes

Circulating adiponectin levels, expression of adiponectin receptors, and methylation of adiponectin gene promoter in relation to Alzheimer’s disease

BackgroundThe role of adiponectin (ADIPOQ) in Alzheimer’s disease (AD) has been documented, however, demonstrating controversial results. In this study, we investigated blood serum ADIPOQ levels, methylation of the adiponectin gene promoter, and adiponectin receptors (AdipoR1 and AdipoR2) expression in blood samples isolated from AD patients and healthy controls.MethodsWe performed a case–control study including 248 subjects (98 AD patients and 150 healthy controls); ADIPOQ serum levels, AdipoR1, and AdipoR2 levels in PBMC were measured by ELISA Kits, and ADIPOQ gene methylation was analyzed using methyl-specific PCR.ResultsSerum adiponectin levels were threefold higher in the AD group compared to the controls. We have also found a positive correlation between adiponectin and MMSE scores and high-density lipoprotein cholesterol (HDL-C) in AD patients. A significant difference in the proportion of methylation of the CpG sites at − 74 nt of the ADIPOQ gene promoter was detected in AD cases, and the levels of adiponectin in blood serum were significantly higher in methylated samples in the AD group compared to controls. The amount of AdipoR1 was significantly higher among AD subjects, while the expression of AdipoR2 did not vary between AD patients and controls.ConclusionThese findings may contribute to a deeper understanding of the etiological factors leading to the development of dementia and may serve as a basis for the development of predictive biomarkers of AD.

No Evidence to Support a Causal Relationship between Circulating Adiponectin Levels and Ankylosing Spondylitis: A Bidirectional Two-Sample Mendelian Randomization Study.

Based on previous observational studies, the causal association between circulating adiponectin (CA) levels and ankylosing spondylitis (AS) risk remains unclear. Therefore, this study aims to investigate whether CA levels are related to the risk of AS. We carried out a bidirectional two-sample Mendelian randomization (MR) analysis to examine the causal correlation between CA levels and AS via published genome-wide association study (GWAS) datasets. Single-nucleotide polymorphisms (SNPs) related to CA levels were derived from a large GWAS that included 39,883 individuals of European descent. SNPs related to AS were obtained from the FinnGen consortium (2252 cases and 227,338 controls). The random-effects inverse variance weighted (IVW) method was the primary method utilized in our research. We also used four complementary approaches to improve the dependability of this study (MR-Egger regression, Weighted median, Weighted mode, and Simple mode). Random-effects IVW (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.79-1.27, p = 0.984) and four complementary methods all indicated that genetically predicted CA levels were not causally related to the risk of AS. In reverse MR analysis, there is little evidence to support the genetic causality between the risk of AS and CA levels.

Genome-wide placental DNA methylations in fetal overgrowth and associations with leptin, adiponectin and fetal growth factors

BackgroundFetal overgrowth “programs” an elevated risk of type 2 diabetes in adulthood. Epigenetic alterations may be a mechanism in programming the vulnerability. We sought to characterize genome-wide alterations in placental gene methylations in fetal overgrowth and the associations with metabolic health biomarkers including leptin, adiponectin and fetal growth factors.ResultsComparing genome-wide placental gene DNA methylations in large-for-gestational-age (LGA, an indicator of fetal overgrowth, n = 30) versus optimal-for-gestational-age (OGA, control, n = 30) infants using the Illumina Infinium Human Methylation-EPIC BeadChip, we identified 543 differential methylation positions (DMPs; 397 hypermethylated, 146 hypomethylated) at false discovery rate < 5% and absolute methylation difference > 0.05 after adjusting for placental cell-type heterogeneity, maternal age, pre-pregnancy BMI and HbA1c levels during pregnancy. Twenty-five DMPs annotated to 20 genes (QSOX1, FCHSD2, LOC101928162, ADGRB3, GCNT1, TAP1, MYO16, NAV1, ATP8A2, LBXCOR1, EN2, INCA1, CAMTA2, SORCS2, SLC4A4, RPA3, UMAD1,USP53, OR2L13 and NR3C2) could explain 80% of the birth weight variations. Pathway analyses did not detect any statistically significant pathways after correcting for multiple tests. We validated a newly discovered differentially (hyper-)methylated gene-visual system homeobox 1 (VSX1) in an independent pyrosequencing study sample (LGA 47, OGA 47). Our data confirmed a hypermethylated gene—cadherin 13 (CDH13) reported in a previous epigenome-wide association study. Adiponectin in cord blood was correlated with its gene methylation in the placenta, while leptin and fetal growth factors (insulin, IGF-1, IGF-2) were not.ConclusionsFetal overgrowth may be associated with a large number of altered placental gene methylations. Placental VSX1 and CDH13 genes are hypermethylated in fetal overgrowth. Placental ADIPOQ gene methylations and fetal circulating adiponectin levels were correlated, suggesting the contribution of placenta-originated adiponectin to cord blood adiponectin.

Seasonal Change in Adiponectin Associated with Ovarian Morphology and Function in Wild Ground Squirrels (Citellus dauricus Brandt)

The goal of this study is to explore the relationship between altered circulating adiponectin concentration, ovarian tissue morphology, ovarian steroidogenesis, and sex hormone production in ovaries of wild ground squirrels. The ovarian mass differed significantly during the breeding and non-breeding seasons, and the circulating estradiol and progesterone concentrations were significantly higher in the breeding season, while the circulating adiponectin level was significantly lower. The expression levels of gonadotropin receptors (FSHR and LHR) and steroidogenic enzymes (StAR, P450scc, P450arom, and 3β-HSD) were significantly higher during the breeding season. Comparing the ovarian transcriptome data of wild ground squirrels between the two periods, we found that some differentially expressed genes were enriched for ovarian steroidogenesis and the adipocytokine signaling pathway, which correlated with our present results. Notably, the MAPK signaling pathway was also enriched and its related genes (Erk1, p38 Mapk, Jnk) were up-regulated by qPCR during the non-breeding season. These findings suggested that adiponectin may be involved in the regulation of seasonal changes in the ovarian function of wild ground squirrels, possibly by acting on the MAPK signaling pathway to regulate sex steroidogenesis in the ovaries.