High Molecular Weight Adiponectin Levels Research Articles

Metabolic disparities between obese and non-obese patients with polycystic ovary syndrome: implications for endometrial receptivity indicators

Objective To investigate the differences in the metabolic indicators and sex hormones between obese and non-obese patients with polycystic ovary syndrome (PCOS), and their impacts on endometrial receptivity (ER). Methods We selected 255 individuals with PCOS, and categorized them into the obese groups, including the OP group (obese patients with PCOS) and the ON group (obese patients without PCOS), and selected 64 individuals who were categorized in the non-obese groups, namely, the control groups, which comprise the NP group (non-obese patients with PCOS) and the NN group(non-obese patients without PCOS). The one-way analysis of variance (ANOVA) and Mann-Whitney U tests were used to compare the metabolic indicators, and sex hormone-associated and ER-associated indicators between the groups. The correlation between the aforementioned clinical markers and ER was analyzed using the Pearson’s correlation coefficient. Results (1) In comparison with the NP group, the OP group exhibited higher levels (p < .01) of free androgen index (FAI), anti-müllerian hormone (AMH), fasting insulin (FINS), insulin level within 60 min, 120 min, and 180 min—60minINS, 120minINS, and 180minINS, respectively, fasting blood glucose (FBG), blood glucose level within two hours (2hGlu), homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), waist-to-hip ratio (WHR), waist circumference, hip circumference, the ratio of the maximum blood flow velocity of the uterine artery during systole to the blood flow velocity of the uterine artery at the end of diastole (uterine artery S/D), and blood flow resistance index (RI) of the uterine artery. In comparison with the NP group, the OP group exhibited lower levels (p < .01) of sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), high molecular weight adiponectin (HMWA), and high-density lipoprotein cholesterol (HDL-C). (2) In the PCOS group, RI was significantly positively correlated with FAI, FINS, 120minINS, HOMA-IR, and WHR (p < .01), and significantly negatively correlated with SHBG, HDL-C, and HMWA (p < .01); uterine artery S/D was significantly positively correlated with FAI, FINS, 2hGlu, HOMA-IR, LDL-C, and WHR (p < .01), significantly positively correlated with 120minINS and FBG (p < .05), and significantly negatively correlated with SHBG and HMWA (p < .01). Conclusion (1) The OP group exhibited obvious metabolic disorders and poor ER, which was manifested as low levels of SHBG and HMWA, and high levels of FAI, HOMA-IR, WHR, uterine artery S/D, and RI. (2) In patients with PCOS, there was a substantial correlation between ER-associated indicators RI and uterine artery S/D and FAI, FINS, 120minINS, HOMA-IR, WHR, SHBG, and HMWA.

Serum levels of HMW adiponectin and its receptors are associated with cytokine levels and clinical characteristics in chronic obstructive pulmonary disease.

We aimed to investigate the changes in the levels of high-molecular-weight (HMW) adiponectin, adiponectin receptors, and cytokines in patients with chronic obstructive pulmonary disease (COPD), as well as their potential relationships. Forty-one patients who underwent lobectomy for lung lesions and had a clear postoperative pathological diagnosis were divided into the non-COPD (N = 23) and COPD (N = 18) groups. HMW adiponectin, cytokine, and T-cadherin levels in serum and tissues were detected by enzyme-linked immunosorbent assay. The levels of HMW adiponectin and cytokine (interleukin [IL]-6, IL-10, surfactant protein D, 4-hydroxynonenal, tumor necrosis factor-α, and C reactive protein) in the serum and tissues increased in the COPD group compared to those in the non-COPD group. Patients with COPD exhibited AdipoR1 upregulation and AdipoR2 downregulation. Although T-cadherin did not differ significantly between patients with and those without COPD, its expression was elevated during the progression from COPD with benign lung lesions to combined lung cancer. Furthermore, the HMW adiponectin levels were significantly correlated with the cytokine levels and the clinical characteristics of COPD. HMW adiponectin and its receptors affect the inflammatory process in COPD and may further contribute to the progression of the disease to malignancy.

Visfatin and Subclinical Atherosclerosis in Type 2 Diabetes: Impact of Cardiovascular Drugs.

Background and Objectives: The role of adipokines in the development of atherosclerosis in type 2 diabetes (T2DM) has not yet been fully elucidated. The effects of drugs on adipokine concentrations have only been evaluated in very few studies, although they may be of clinical importance. This study aimed to assess whether the concentrations of circulating adipokines could predict subclinical atherosclerosis in patients with T2DM, as well as their interactions with commonly used cardiovascular drugs. Materials and Methods: Our population-based cross-sectional multicentric study included 216 participants with T2DM but without previously diagnosed atherosclerosis. The carotid artery intima-media thickness (IMT), plaque and ankle-brachial index (ABI) metrics were measured. Resistin, visfatin, retinol-binding protein 4, high molecular weight adiponectin and leptin levels were evaluated using Luminex's xMAP technology. Results: Visfatin and resistin concentrations correlated positively with IMT (p = 0.002 and p = 0.009, respectively). The correlation of visfatin to IMT ≥ 1.0 mm was significant in males (p < 0.001). Visfatin had a positive correlation with IMT ≥ 1.0 mm or plaque (p = 0.008) but resistin only correlated with plaque (p = 0.049). Visfatin predicted IMT ≥ 1.0 mm or plaque in patients on β-blocker monotherapy (p = 0.031). Visfatin lost its ability to predict subclinical atherosclerosis in patients taking angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers or statins. After adjustments for risk factors for atherosclerosis and cardiovascular drugs, visfatin maintained an independent association with mean IMT (p = 0.003), IMT ≥ 1.0 mm or plaque (p = 0.005) and ABI ≤ 0.9 (p = 0.029). Conclusions: Visfatin could be used as a marker of subclinical atherosclerosis in patients with T2DM, especially in males. The assessment of visfatin concentration could aid in identifying individuals who could benefit from implementing preventive measures against atherosclerosis.

High molecular weight adiponectin as a biomarker of hypertension in children and adolescents with obesity.

Lower HMW (high molecular weight) adiponectin levels are associated with obesity, insulin resistance, and metabolic syndrome in children and adolescents. However, data on HMW levels in pediatric population with hypertension are lacking. This study aimed to examine the association and predictive capacity of HMW levels, HMW/HOMA-IR, and HMW/APN ratio with hypertension in obese children and adolescents. The 299 pediatric subjects were grouped in obese hypertensive (OH), obese normotensive (ON), and normal weight normotensive (NN). Plasma concentrations of HMW were investigated by ELISA. ANOVA was used to compare study groups, and a binary logistic regression analysis was used to verify if HMW, HMW/HOMA-IR, HMW/APN, APN, APN/HOMA-IR, and HOMA-IR are associated to hypertension regardless obesity in children and adolescents. To compare the strength and performance of each biomarker to classify individuals with and without hypertension, the receiver-operating characteristic (ROC) curve, area under the curve (AUC), and Youden index (J) were evaluated. Both HMW plasma levels and the HMW/HOMA-IR ratio were significantly lower in the OH group when compared to the ON group (HMW: 2.00 ± 1.33µg/mL vs 2.48 ± 1.48µg/mL; HMW/HOMA-IR ratio: 0.87 ± 0.95 vs 1.27 ± 1.2; P < 0.05) and NN weight groups (HMW: 2.00 ± 1.33µg/mL vs 4.02 ± 1.99µg/mL; HMW/HOMA-IR ratio: 0.87 ± 0.95 vs 2.62 ± 1.86; P < 0.05). Hypertension was associated with lowest HMW (OR = 4.50; 95% CI = 1.41-15.84) and HMW/HOMA-IR (OR = 12.13; 95% CI = 2.51-92.93) regardless of obesity. However, HOMA-IR or the HMW/APN was not significant (P > 0.05). In the ROC curve analyses, the HMW and HMW/HOM-IR were more sensitive to detect hypertension in children and adolescents with obesity. Conclusion: Low levels of HMW oligomer and HMW/HOM-IR are associated with hypertension in childhood obesity. Thus, these biomarkers could be clinically useful in identifying hypertension in childhood obesity. What is Known: • HMW has previously been reported as the most biologically active isoform of adiponectin, and lower HMW concentrations are associated with obesity, insulin resistance, and metabolic syndrome in children and adolescents. • HMW/HOMA-IR ratio is a sensitive predictor for metabolic syndrome in adults. What is New: • HMW levels are associated with hypertension in children and adolescents, independently of presence of obesity. • HMW was more sensitive to detect hypertension in children and adolescents with obesity when compared to HMW/HOMA-IR, HMW/APN, APN, APN/HOMA-IR, or HOMA-IR.

Plasma free amino acid profiles are associated with serum high molecular weight adiponectin levels in Japanese medical check-up population without type 2 diabetes mellitus

To prevent the progression of type 2 diabetes mellitus (T2DM), early detection and intervention are important. Several studies have already shown that the serum adiponectin level could be useful for evaluating the future risk of T2DM. Recently, plasma free amino acid (PFAA) concentrations have also emerged as potential biomarkers that predict the future onset of T2DM. In this study, we aimed to further characterise PFAA profiles by elucidating the association with the serum high molecular weight (HMW) adiponectin level in this cross-sectional study. A total of 1000 Japanese subjects who underwent medical check-ups were enrolled, and their plasma concentrations of 21 amino acids and clinical parameters were measured. The subjects without T2DM were divided into quartiles (Q1-4) by serum HMW adiponectin level, and the association with between PFAA concentrations was analysed. Concentrations of glutamate, alanine, proline, tyrosine, histidine, methionine, lysine, branched-chain amino acids (BCAAs) and tryptophan varied significantly according to the adiponectin quartile. Furthermore, serum adiponectin levels showed significant inverse correlations with these amino acids. The change in the PFAA profile in the group with the lowest adiponectin concentrations (Q1) was similar to that of T2DM patients. Although both adiponectin levels and PFAA concentrations are known to be altered by the accumulation of visceral fat and insulin resistance, the levels of glutamate, BCAA, lysine and tryptophan remain significantly associated with adiponectin level after adjustment for age, body mass index and homeostasis model assessment of insulin resistance, showing the direct association between PFAA concentrations and the serum HMW adiponectin level. Registration number: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) UMIN000029920, registered on Nov 13th 2017 (prospectively registered).

Levels of hormones regulating appetite and energy homeostasis in response to a 1.5-Year combined lifestyle intervention for obesity.

Background: Weight loss can induce changes in appetite-regulating hormone levels, possibly linked to increases in appetite and weight regain. However, hormonal changes vary across interventions. Here, we studied levels of appetite-regulating hormones during a combined lifestyle intervention (CLI: healthy diet, exercise and cognitive behavioral therapy). Methods: We measured levels of long-term adiposity-related hormones (leptin, insulin, high-molecular-weight (HMW) adiponectin) and short-term appetite hormones (PYY, cholecystokinin, gastric-inhibitory polypeptide, pancreatic polypeptide, FGF21, AgRP) in overnight-fasted serum of 39 patients with obesity. Hormone levels were compared between T0 (baseline), T1 (after 10 weeks) and T2 (end of treatment, 1.5years). T0-T1 hormone changes were correlated with T1-T2 anthropometric changes. Results: Initial weight loss at T1 was maintained at T2 (-5.0%, p < 0.001), and accompanied by decreased leptin and insulin levels at T1 and T2 (all p < 0.05) compared to T0. Most short-term signals were not affected. Only PP levels were decreased at T2 compared to T0 (p < 0.05). Most changes in hormone levels during initial weight loss did not predict subsequent changes in anthropometrics, except for T0-T1 decreases in FGF21 levels and T0-T1 increases in HMW adiponectin levels tended to be associated with larger T1-T2 increases in BMI (p < 0.05 and p = 0.05, respectively). Conclusion: CLI-induced weight loss was associated with changes in levels of long-term adiposity-related hormones towards healthy levels, but not with orexigenic changes in most short-term appetite signals. Our data indicates that the clinical impact of alterations in appetite-regulating hormones during modest weight loss remains questionable. Future studies should investigate potential associations of weight-loss-induced changes in FGF21 and adiponectin levels with weight regain.

Relationship between circulating adipokines and cholesterol efflux in subjects with severe carotid atherosclerosis

AimsCholesterol efflux capacity (CEC) as a measure of high-density lipoprotein functionality is independently and inversely associated with increased risk of cardiovascular events and mortality, and advanced plaque morphology. Adipokines, adipose tissue-derived factors, can influence systemic lipoprotein metabolism, and participate in the regulation of vascular function and inflammation. We aimed to investigate the association between CEC and circulating adipokine levels (anti-inflammatory adiponectin, and pro-inflammatory chemerin and resistin) in subjects with severe carotid atherosclerotic disease and evaluate its impact on post-surgical outcomes. Methods and resultsThis is a cross-sectional study with a 5-year follow-up component. Consecutive patients with severe carotid atherosclerosis scheduled for a carotid endarterectomy were recruited from hospital-based centres in Montreal, Canada (n = 285). Fasting blood samples were collected pre-operatively and used to measure plasma total and high-molecular weight (HMW) adiponectin, chemerin, and resistin, and to perform cholesterol efflux assays in J774 macrophage-like cells. Five-year post-surgery outcomes were obtained through medical chart review. Subjects had a mean age of 70.1 ± 9.4, were 67.0 % male, had various comorbidities (hypercholesterolemia [85.3 %], hypertension [83.5 %], type 2 diabetes [34.5 %], coronary artery disease [38.6 %]), and previously experienced cerebrovascular symptomatology (77.9 %). CEC was independently and positively associated with total and HMW adiponectin levels (ß [95 % confidence interval]; 0.216 [0.134–0.298] and 0.107 [0.037–0.176], respectively) but not with chemerin or resistin. Total adiponectin had the greatest association accounting for 8.3 % of the variance in CEC. Interaction regression models demonstrated a significant interaction between adiponectin and chemerin in increasing CEC. Notably, with each unit increase in CEC there was a 93.9 % decrease in the odds of having an ischemic cerebrovascular event 5 years post-surgery (0.061 [0.007–0.561]). ConclusionsOur findings demonstrated circulating adiponectin to have a strong association with increased CEC in subjects with severe carotid atherosclerosis and high CEC to be associated with more favourable post-surgical outcomes. These findings reflect the importance of adipose tissue health in influencing CEC levels and atherosclerotic cardiovascular disease risk.

1382-P: Novel Mechanisms to Reconvert Glucocorticoids into Pro-Metabolic Agents through Adiponectin

Adiponectin is the most abundant adipokine in our circulation and regulates inter-tissue communication like the adipose-muscle axis. Pharmacological modulation of this crosstalk is beneficial in promoting exercise tolerance in metabolic stress conditions like obesity. Endogenous glucocorticoids regulate metabolic function and stress response, but chronic daily intake of exogenous glucocorticoids produces or exacerbates metabolic stress. However, in stark contrast to daily intake, we discovered that intermittent regimens of glucocorticoids, e.g. once-weekly, improves exercise tolerance. However, the mechanisms underlying the differential regimen-specific effects of glucocorticoids in obesity remain unknown. Here we investigated the mechanisms differentiating once-weekly versus once-daily regimens of the same glucocorticoid prednisone in obesity. In mice with diet-induced obesity, once-weekly prednisone stimulated total and high-molecular weight adiponectin levels, improving exercise tolerance and energy expenditure. These effects were dependent upon adiponectin and were blocked by genetic ablation of the adipokine. Upregulation of Adipoq occurred through the adipose-specific glucocorticoid receptor (GR) , as this effect was blocked in mice with inducible GR ablation in adipose tissue. In contrast, once-daily prednisone decreased adiponectin levels through upregulation of known repressors of adiponectin expression in adipose tissue. The drug regimens remodeled in opposite ways also transcriptome and function in skeletal muscle after onset of obesity. Particularly, once-weekly prednisone treatment increased the muscle metabolic response to adiponectin through the CAMKK2-AMPK cascade. Our study demonstrates that intermittent glucocorticoids produce healthful metabolic remodeling in diet-induced obesity through direct upregulation of adiponectin expression in adipose tissue and adiponectin-dependent signaling in skeletal muscle. Disclosure M.Wintzinger: Employee; Cincinnati Children's Hospital. K.Miz: None. M.Panta: None. H.Durumutla: None. A.Pragasam: None. M.Quattrocelli: None. Funding National Institutes of Health grant DK121875National Institutes of Health grant HL158531CCHMC Trustee AwardCCHMC Heart Institute Translational Grant

Intermittent prednisone treatment in mice promotes exercise tolerance in obesity through adiponectin.

The fat-muscle communication regulates metabolism and involves circulating signals like adiponectin. Modulation of this cross-talk could benefit muscle bioenergetics and exercise tolerance in conditions like obesity. Chronic daily intake of exogenous glucocorticoids produces or exacerbates metabolic stress, often leading to obesity. In stark contrast to the daily intake, we discovered that intermittent pulses of glucocorticoids improve dystrophic muscle metabolism. However, the underlying mechanisms, particularly in the context of obesity, are still largely unknown. Here we report that in mice with diet-induced obesity, intermittent once-weekly prednisone increased total and high-molecular weight adiponectin levels and improved exercise tolerance and energy expenditure. These effects were dependent upon adiponectin, as shown by genetic ablation of the adipokine. Upregulation of Adipoq occurred through the glucocorticoid receptor (GR), as this effect was blocked by inducible GR ablation in adipocytes. The treatment increased the muscle metabolic response of adiponectin through the CAMKK2-AMPK cascade. Our study demonstrates that intermittent glucocorticoids produce healthful metabolic remodeling in diet-induced obesity.

Relationship between adiponectin multimer levels and subtypes of cerebral infarction.

Serum adiponectin levels are decreased in patients with cerebral infarction. Adiponectin in circulation exists in three isoforms: high molecular weight (HMW), medium molecular weight (MMW), and low molecular weight (LMW) adiponectin. We measured serum levels of total adiponectin and adiponectin multimers (HMW, MMW, and LMW) in patients with cerebral infarction and compared the serum levels of the three adiponectin multimers in stroke subtypes. We also evaluated the clinical value of adiponectin multimer levels as a biomarker for cerebral infarction. We assessed a total of 132 patients with cerebral infarctions. The serum levels of total and adiponectin multimers were measured using enzyme-linked immunosorbent assay (ELISA). The total and HMW adiponectin levels were significantly lower in atherothrombotic infarction (AI) than in cerebral embolism (CE) (total, p < 0.05; HMW, p < 0.05). In male patients, the MMW adiponectin level was significantly lower in the lacunar infarction (LI) group than in the AI group (p < 0.05). The LMW adiponectin level was significantly lower in the AI group than in the LI and CE groups (LI, p < 0.001; CE, p = 0.001). However, there were no significant differences in adiponectin multimer levels among the stroke subtypes in female subjects. Additionally, in female patients with AI and LI, the LMW adiponectin levels were negatively associated with C-reactive protein (CRP; AI, p < 0.05; LI, p < 0.05). These findings suggest that a decrease in adiponectin is associated with AI and that serum LMW adiponectin level represents a potential biomarker for AI.

Serum Expression of ESM-1, HMWA, and AGEs and Its Relationship with Disease Severity in Patients with Gestational Hypertension.

Objective The research is to investigate the expression and the relationship between serum endothelial cell-specific molecular molecule-1 (ESM-1), high molecular weight adiponectin (HMWA), and late glycosylation terminal product (AGEs) in patients with gestational hypertension. Methods 75 patients with pregnant hypertension who were treated in our hospital from June 2019 to June 2020 were selected as the case group, and 70 healthy pregnant women with pregnancy examination at the same period in our hospital were selected as the control group to analyze the changes in serum ESM-1, HMWA, and AGEs levels and the correlation with the degree of illness and their predictive value. Results Serum ESM-1 and AGEs were significantly higher in the case group than in the control group. Serum HMWA was significantly lower than that in the control group (P < 0.05). The gestational hypertensive serum ESM-1 and AGEs was significantly lower than in patients with mild preeclampsia and severe preeclampsia. Serum HMWA was significantly higher than in patients with mild preeclampsia and severe preeclampsia. Serum ESM-1 and AGEs of mild preeclampsia were significantly lower than in patients with severe preeclampsia. Serum HMWA was significantly higher than in patients with severe preeclampsia (P < 0.05). The result of correlation analysis shows a positive correlation between serum ESM-1 and AGEs (P < 0.05). A negative correlation was observed between HMWA and the degree of illness (P < 0.05). Conclusion Serum ESM-1, HMWA, and AGEs are abnormally expressed in gestational hypertension, are closely related to the degree of condition, and have important clinical significance for condition control.

Active Consumption of Konjac and Konjac Products Improves Blood Glucose Control in Patients with Type 2 Diabetes Mellitus

Objective Konjac is a food mainly consumed in Asian countries with high fiber and low energy. Although glucomannan, a component of konjac, have been used for several clinical studies, there is few reports using konjac itself. This study examined the effects of the active consumption of konjac in patients with type 2 diabetes mellitus (T2DM). Methods The study included 26 Japanese patients with T2DM. Participants were recommended to take konjac at least once a day using free konjac products (various noodles, rice, and desserts) and plate konjac for 12 weeks. Results HbA1c and fasting plasma glucose levels significantly decreased from 8.3 ± 0.9% to 8.0 ± 0.8% and from 173.2 ± 44.4 to 152.8 ± 36.7 mg/dL, respectively. No significant changes were observed in body weight and insulin resistance indices, but the index for insulin secretion significantly increased. Serum high molecular weight adiponectin levels significantly increased. Plasma ghrelin, leptin and glucagon-like peptide-1 levels tended to decrease (p = 0.084), decrease (p = 0.057) and increase (p = 0.071), respectively. Actual konjac intake positively correlated with age (r = 0.61, p = 0.001). Body weight and HbA1c significantly decreased in patients aged ≥50 years than in those aged <50 years, and the changes significantly inversely correlated with age. Conclusion Active consumption of konjac and konjac products seems to be a useful dietary therapy with multifaceted action for T2DM. Further studies with greater sample size and long-term are needed to confirm these findings.

Effects of Oral Vitamin C Supplementation on Liver Health and Associated Parameters in Patients With Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial.

Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent hepatic disorder worldwide, and an unhealthy lifestyle is the leading risk factor for its occurrence. Vitamin C (VC) has been suggested to protect NAFLD, whereas evidence from randomized controlled trials (RCTs) is sparse. In this study, we aimed to investigate the potential benefits of VC supplementation daily on liver health and associated parameters in patients with NAFLD. In this double-blind, RCT, 84 patients with NAFLD, aged 18–60 years old, were assigned to 12 weeks of oral treatment with either low (250 mg/day, n = 26), medium (1,000 mg/day, n = 30), or high (2,000 mg/day, n = 28) doses of VC supplements. After the intervention, the Medium group had a more significant decrease in aspartate aminotransferase [Medium, −5.00 (−10.25, −1.75) vs. High, −2.50 (−7.75, 0.00), P = 0.02] and alanine aminotransferase [Medium, −8.00 (−18.00, −1.75) vs. High, −3.50 (−13.75, 4.25), P = 0.05; Medium vs. Low, −3.00 (−9.00, 5.50), P = 0.031]. The levels of other indicators of liver health, such as gamma-glutamyl transferase, alkaline phosphatase, total bilirubin, and direct bilirubin were decreased after the intervention but comparable among the three groups and so did the parameters of glucose metabolism, such as fasting insulin, fasting glucose, and homeostasis model assessment for insulin resistance. The plasma level of VC in patients and total adiponectin and high molecular weight (HMW) adiponectin levels were also elevated but not in a dose-dependent manner. Meanwhile, analysis of fecal microbiota composition showed an increase in the alpha diversity (Abundance-based Coverage Estimator (ACE), Shannon, chao1, and Simpson) both in the Low and the Medium groups. A total of 12 weeks of VC supplementation, especially 1,000 mg/day, improved liver health and glucose metabolism in patients with NAFLD. The elevated plasma levels of VC, total and HMW adiponectin, and the improvement of intestinal microbiota may have made some contributions.

Serum high-molecular-weight adiponectin and response to dapagliflozin in patients with type 2 diabetes and non-alcoholic fatty liver disease

A better baseline renal function is associated with a better response to sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes. Low serum adiponectin is associated with visceral fat accumulation...

Relationships between plasma apelin and adiponectin with normal weight obesity, body composition, and cardiorespiratory fitness in working adults

BackgroundA significant proportion of adults have normal weight obesity (NWO), defined as a normal body mass index (BMI) but disproportionately high body fat percentage. Individuals with NWO may have increased risk of cardiometabolic disorders and lower exercise tolerance, but it is unclear if this obesity phenotype is linked with dysregulated production of adipokines or myokines such as adiponectin and apelin, respectively. MethodsThis cross-sectional, secondary analysis included 177 working adults (mean age 49.6 ± 9.9 yrs, 64% female). Plasma high-molecular weight adiponectin and apelin levels were measured by ELISA. Body composition and fat distribution were assessed using dual energy X-ray absorptiometry. Exercise tolerance (VO2 maximum) was determined by treadmill testing. NWO was defined as a BMI <25 kg/m2 and body fat >30% for women or >23% for men. Participants were categorized as lean, NWO, or overweight-obese. ResultsA total of 14.7% of subjects were categorized as lean, 23.7% as having NWO, and 61.6% as having overweight-obesity. Plasma adiponectin levels were elevated in the overweight-obesity group (P < 0.05) compared to the lean and NWO groups, which did not differ from each other (P > 0.05). Adiponectin concentrations were inversely associated with BMI, fat mass, fat mass percent, visceral fat, and trunk to leg fat ratio and positively associated with leg fat mass (all P < 0.001). Plasma apelin levels were similar between the three body composition groups (P < 0.05) and were not significantly associated with any body composition indices. Apelin concentrations were inversely related to VO2 maximum (β = −0.03 ± 0.01, p = 0.002). ConclusionPlasma adiponectin and apelin levels did not distinguish between lean and NWO groups. Positive relationships with leg fat mass and adiponectin suggest the importance of assessing body composition and fat distribution when studying adipokines and cardiometabolic disorders. Further investigations are needed to understand relationships between exercise, body composition, and apelin secretion.

Longitudinal Changes of High Molecular Weight Adiponectin are Associated with Postpartum Development of Type 2 Diabetes Mellitus in Patients with Gestational Diabetes Mellitus.

BackgroundThe influence of serial changes of adipokines on maternal glucose metabolism from pregnancy to postpartum periods in women with previous gestational diabetes mellitus (pGDM) has not been thoroughly explored. We tried to examine the relationship between the serial changes of adipokines and the development of diabetes mellitus (DM) in women with pGDM.MethodsWe longitudinally measured following adipokines: high molecular weight (HMW) adiponectin, retinol-binding protein-4 (RBP-4), lipocalin-2, and chemerin, during pregnancy, and at 2 months and 3 years after delivery. Based on glucose status at postpartum 3 years, we divided into three groups: normal glucose tolerance (GDM-NGT, n=20), impaired glucose tolerance (GDM-IGT, n=23), and GDM-DM (n=22). We analyzed the correlations between adipokines and various metabolic parameters.ResultsPlasma HMW adiponectin levels were not different among the three groups during pregnancy. However, HMW adiponectin levels increased at 3 years after the delivery in women with GDM-NGT compared with women with GDM-DM. In the GDM-IGT group, HMW adiponectin levels increased at 2 months postpartum compared to pregnancy period. In contrast, HMW adiponectin levels showed no alternation after parturition in women with GDM-DM. HMW adiponectin was negatively correlated with body mass index and a homeostasis model assessment of insulin resistance. Other adipokines such as RBP-4, lipocalin-2, and chemerin neither showed any differences among the groups nor any significant correlations with 3 years postpartum status of glucose intolerance.ConclusionSerial changes of HMW adiponectin are associated with the maintenance of glucose metabolism in women with pGDM after delivery.

Dietary Omega-6 to Omega-3 Fatty Acids Ratio is Correlated with High Molecular Weight Adiponectin Level in Indonesian Office Workers

Context: Adiponectin is an adipokine that is secreted by adipocytes and acts to prevent obesity and obesity-related disorders. The high ratio of omega-6 to omega-3 fatty acids in modern dietary habits in working-age populations, urban areas in particular, is known to play a role in adiponectin secretion. However, previous studies showed inconclusive results. Aim: The study aims to determine the association of the dietary omega-6 to omega-3 fatty acids ratio with adiponectin levels in office workers in Jakarta, Indonesia. Settings and Design: This cross-sectional study included 55 office workers in East Jakarta, Indonesia. Methods: Data were collected via questionnaire, 3-day food record, anthropometric measurement, and serum collection. Statistical analysis used: Independent t test was applied to assess the relationship between subjects characteristics and dietary intake with high molecular weight adiponectin levels. Association of dietary omega-6/omega-3 fatty acids ratio and adiponectin were evaluated using Pearson correlation test (P < 0.05). Results: There is no statistically significant difference in adiponectin levels based on waist circumference category, as well as categories of physical activity, household income levels, total energy, and total fat intake. Conversely, in female subjects (P = 0.000), subjects with normal body mass index (P = 0.000), higher education levels (P = 0.031), and nonsmoking subjects (P = 0.019), significantly higher adiponectin levels are obtained. The ratio of dietary omega-6/omega-3 fatty acids is negatively correlated with adiponectin (P = 0.004, r = –0.383). Conclusions: The decrease in the ratio of omega-6/omega-3 fatty acids is inversely related to higher level of adiponectin, indicating that dietary changes may potentially play a role in prevention strategies for obesity and obesity-related diseases.

High levels of leptin and non-high molecular weight-adiponectin in patients with colorectal cancer: Association with chemotherapy and common genetic polymorphisms.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide. Leptin and adiponectin are hormones produced by adipose tissues, which exhibit opposing effects on tumor growth. Leptin promotes tumor development and metastasis, whereas adiponectin attenuates this. The aim of the present study was to assess the possible association between leptin and adiponectin [both high molecular weight (HMW) and non-HMW factions] levels with CRC, CRC response to chemotherapy, and to study the relationship between LEPR (rs6588147), ADIPO (rs266729), LEP (rs2167270), and ADIPO (rs822369) polymorphisms and CRC. A total of 32 blood samples collected from CRC patients were analyzed to identify the serum levels of leptin and adiponectin, and the presence of CRC related polymorphisms. A total of 25 healthy subjects were recruited in the control group. Serum levels of leptin and adiponectin were detected using ELISA whereas DNA from patients and controls was amplified and analyzed using PCR-restriction fragment length polymorphism assay. The results showed that the levels of leptin and non-HMW adiponectin were significantly higher in CRC patients compared with the controls (P<0.05). In addition, HMW adiponectin was significantly higher in patients receiving chemotherapy. The association between LEPR (rs6588147), ADIPO (rs266729), LEP (rs2167270) and ADIPO (rs822369) polymorphisms and CRC was not significant (P>0.05). In conclusion, higher leptin and non-HMW adiponectin levels may be associated with increased CRC. Chemotherapy may positively influence the levels of HMW adiponectin. No association between LEPR (rs6588147), ADIPO (rs266729), LEP (rs2167270) and ADIPO (rs822369) polymorphisms with CRC was found.

High molecular weight adiponectin levels are inversely associated with adiposity in pediatric brain tumor survivors

While children with brain tumors are surviving at record rates, survivors are at risk of cardiovascular disease and type 2 diabetes mellitus; these conditions may be driven by excess body fat. Adiponectin in an adipokine that is inversely associated with the fat mass, and has been linked to cardiometabolic risk stratification in the general population. However, adiponectin’s profile and determinants in SCBT have not been established. We tested the hypothesis that high molecular weight (HMW) adiponectin levels, the more biologically active form of adiponectin, were associated with adiposity in SCBT similarly to non-cancer controls. Seventy-four SCBT (n = 32 female) and 126 controls (n = 59 female) who were 5–17 years old were included. Partial correlations and multivariable regression analyses assessed the relationship between HMW adiponectin and adiposity. HMW adiponectin was inversely associated with total and central adiposity (FM%: β − 0.21, 95% CI − 0.15, − 0.08; p value < 0.0001; WHR: β − 0.14, 95% CI − 0.02, − 0.01; p value < 0.0001 ;WHtR: β − 0.21, 95% CI − 0.05, − 0.03; p value < 0.0001). In conclusion, HMW adiponectin is inversely correlated with adiposity in SCBT. Adiponectin may serve as a biomarker of cardiometabolic risk and response to interventions to prevent and manage obesity and its comorbidities in SCBT.

Adiponectin is secreted via caveolin 1-dependent mechanisms in white adipocytes.

Here we have investigated the role of the protein caveolin 1 (Cav1) and caveolae in the secretion of the white adipocyte hormone adiponectin. Using mouse primary subcutaneous adipocytes genetically depleted of Cav1, we show that the adiponectin secretion, stimulated either adrenergically or by insulin, is abrogated while basal (unstimulated) release of adiponectin is elevated. Adiponectin secretion is similarly affected in wildtype mouse and human adipocytes where the caveolae structure was chemically disrupted. The altered ex vivo secretion in adipocytes isolated from Cav1 null mice is accompanied by lowered serum levels of the high-molecular weight (HMW) form of adiponectin, whereas the total concentration of adiponectin is unaltered. Interestingly, levels of HMW adiponectin are maintained in adipose tissue from Cav1-depleted mice, signifying that a secretory defect is present. The gene expression of key regulatory proteins known to be involved in cAMP/adrenergically triggered adiponectin exocytosis (the beta-3-adrenergic receptor and exchange protein directly activated by cAMP) remains intact in Cav1 null adipocytes. Microscopy and fractionation studies indicate that adiponectin vesicles do not co-localise with Cav1 but that some vesicles are associated with a specific fraction of caveolae. Our studies propose that Cav1 has an important role in secretion of HMW adiponectin, even though adiponectin-containing vesicles are not obviously associated with this protein. We suggest that Cav1, and/or the caveolae domain, is essential for the organisation of signalling pathways involved in the regulation of HMW adiponectin exocytosis, a function that is disrupted in Cav1/caveolae-depleted adipocytes.