High Molecular Weight Adiponectin Research Articles

Integrated neuromuscular training intervention applied in schools induces a higher increase in salivary high molecular weight adiponectin and a more favorable body mass index, cardiorespiratory fitness and muscle strength in children as compared to the traditional physical education classes.

High-molecular-weight adiponectin (HMW-adiponectin) is a cardio-metabolic health protector. Objectives: (1) to compare body mass index (BMI), cardiorespiratory fitness (CRF) and muscle strength (MS) in healthy school-children depending on their baseline salivary-HMW-adiponectin concentration; and (2) to apply a 3-month integrated neuromuscular training (INT) and evaluate its effects on salivary-HMW-adiponectin concentration, BMI, CRF and MS in the same children. Additional goal: to identify if any potential changes during the 3-month period may be related to a potential change in salivary-HMW-adiponectin concentration. Ninety children (7.4 ± 0.3 years) were recruited in primary schools and randomly allocated into control or intervention group. The intervention consisted of a 3-month INT applied during physical education (PE) classes, twice-weekly, while the control group had traditional PE classes. Body mass and height were measured, BMI was calculated and HMW-adiponectin was quantified in saliva. To assess CRF and MS, 800 m-run and hand-dynamometry were applied, respectively. All measurements were performed twice, at baseline and after 3 months. Children with higher baseline salivary-HMW-adiponectin have more favorable BMI (p = 0.006) and slightly higher CRF (p = 0.017) in comparison to the children with lower baseline salivary-HMW-adiponectin. There were no big changes after the 3-month-period neither in the control, nor the INT group. However, it is worthy to note that the INT induced slightly higher increase in salivary-HMW-adiponectin (p = 0.007), and a slightly higher improvement in BMI (p = 0.028), CRF (p = 0.043) and MS (p = 0.003), as compared to the traditional PE classes. Finally, the INT-induced improvement in CRF was associated with the increased post-salivary-HMW-adiponectin concentration (p = 0.022). Main findings may suggest the potential utility of an INT as a cost-effective strategy that can be applied in schools to induce cardio-protective effects in school-children.

Isolation and purification of high molecular weight adiponectin from human plasma fraction

Adiponectin, a crucial protein hormone originating from adipose tissue, regulates key metabolic processes, including lipid metabolism, mitochondrial activity, and insulin sensitivity. These pleiotropic roles of adiponectin, along with its inverse correlation with metabolic disorders such as obesity, type II diabetes, and atherosclerosis, establish this protein as a potential therapeutic target. However, due to this complexity, challenges have arisen in its production with a natural conformation in bacterial or mammalian expression systems, hindering clinical translation. Furthermore, while inducers for adiponectin secretion or chemical agonists targeting adiponectin receptors have shown promise in laboratory settings, clinical studies with these agents have not yet been conducted. This study proposes a method for isolating and purifying natural high molecular weight (HMW) adiponectin from discarded plasma fractions during the conventional pharmaceutical protein manufacturing process. The process involved Cohn-Oncley fractionation, initial chromatography using reduced cellufine formyl, and subsequent purification via DEAE Sepharose chromatography. Characterization involved gel electrophoresis and biological assays on a hepatocyte cell-line. The purification process effectively captured adiponectin from the I + III paste, demonstrating that this fraction contained a significant portion of total plasma adiponectin. The two-step chromatography led to highly purified HMW adiponectin, confirmed by native-PAGE showing a 780 kDa multimeric complex. Biological assessments demonstrated normal downstream signaling, with HMW adiponectin inducing AMPK phosphorylation. This study demonstrates the feasibility of obtaining purified HMW adiponectin by repurposing plasma fractionation processes. It offers a promising avenue for the HMW adiponectin production, tapping into HMW adiponectin’s therapeutic potential against metabolic disorders while optimizing plasma resource utilization in healthcare.

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.

The Association of Plasma Leptin, Soluble Leptin Receptor and Total and High-Molecular Weight Adiponectin With the Risk of Perioperative Neurocognitive Disorders

BackgroundPerioperative neurocognitive disorders (NCD) are poorly characterized in terms of their risk factor profiles. Leptin and adiponectin are adipose-tissue-derived hormones with a role in inflammation and atherosclerosis whose function in perioperative NCD is unclear. Here, we used a cohort of older adults to examine the association of preoperative plasma concentrations of these biomarkers with the risk of perioperative NCD. MethodsProspective analysis of 768 participants aged ≥ 65 years of the BioCog study. Blood was collected before surgery for measurement of plasma total and high-molecular-weight (hmw) adiponectin, leptin, and soluble leptin receptor (sOB-R). The free leptin index (FLI, leptin:sOB-R) was calculated. Postoperative delirium (POD) was assessed twice daily until postoperative day 7/discharge. Five hundred twenty-six patients (68.5%) returned for 3-month follow-up and provided data on postoperative cognitive dysfunction (POCD). POCD was defined as a decline on six neuropsychological tests that exceeded that of a nonsurgical control group. Logistic regression analyses examined the associations of each exposure with POD and POCD risk, in separate models adjusted for age, sex, fasting, surgery type, and body mass index (BMI). ResultsOf 768 patients, 152 (19.8%) developed POD. Of 526 attendants of the follow-up, 54 (10.3%) had developed POCD. Leptin, sOB-R, and total and hmw adiponectin were each not associated with POD. For POCD, we observed reduced risk in patients in FLI quartile 4 compared with quartile 1 (odds ratio, 0.26; 95% CI 0.08, 0.89). Sensitivity analyses for the outcome POD revealed statistically significant interaction terms of sOB-R and total adiponectin with obesity (BMI≥30kg/m2 versus BMI<30kg/m2). For the outcome POCD, a higher sOB-R was associated with an increased risk in the obese subgroup (odds ratio, 4.00; 95% CI 1.01, 15.86). ConclusionsWe did not find consistent evidence for the role of leptin, its receptor, and total and hmw adiponectin in POD and POCD risk. Future research should be used to support or refute our findings and to fully characterize any differences in the associations of these hormones with POD/POCD between obese and nonobese individuals.

Serum levels of adiponectin differentiate generalized lipodystrophies from anorexia nervosa.

The differential diagnosis of lipodystrophy involves other disorders characterized by severe fat loss and may be sometimes challenging. Owing to the rarity of lipodystrophy, it is relevant to search for tools and assays that differentiate it from other diseases that may mimic it. We conducted a study on leptin and high molecular weight (HMW) adiponectin serum concentrations in a series of patients diagnosed with lipodystrophy and compared them with those found in anorexia nervosa, one of the illnesses that may be cause of a missed diagnosis of lipodystrophy. Leptin and HMW adiponectin serum concentrations were measured in six patients diagnosed with generalized lipodystrophy (GL), six with progeroid syndromes (PS), 13 with familial partial lipodystrophy type 1 (FPLD1, Kobberling syndrome), 10 with familial partial lipodystrophy type 2 (FPLD2, Dunnigan syndrome), 18 with acquired partial lipodystrophy (APL) and 12 affected by anorexia nervosa (AN). Measurements were compared to those obtained in 12 normal weight healthy subjects. Serum leptin concentrations were reduced to a similar degree in GL, PS and AN, proportionally to the extent of fat loss. Serum concentrations of HMW adiponectin were found extremely low in patients with GL and PS, while comparable to normal weight subjects in patients with AN. Serum HMW adiponectin can be regarded as a useful tool to discriminate between generalized lipodystrophy syndromes (including PS) and AN.

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.

Associations of levels of high-molecular-weight adiponectin, secreted frizzled-related protein 5 and vascular endothelial growth factor-165 with diabetic retinopathy

Abstract Background: The pathogenesis of diabetic retinopathy (DR) remains unclear. The aim of the study was to explore the associations of DR with the levels of high-molecular-weight adiponectin (HMW-ADP), secreted frizzled-related protein 5 (SFRP-5) as well as vascular endothelial growth factor-165 (VEGF165). Methods: Based on the diagnostic criteria for DR, non-DR (NDR), proliferative DR (PDR) plus non-proliferative DR (NPDR) groups were set up for type 2 diabetes mellitus (T2DM) patients (n=180) treated from January 2020 to March 2021. The control group consisted of another 60 healthy subjects undergoing physical examinations. Their clinical data were compared. Receiver operating characteristic curves were plotted to assess the predictive values of HMW-ADP, VEGF165 and SFRP-5 for DR. The predictive efficiency of the established nomogram model was assessed. Results: The differences in age, fasting plasma glucose (FPG), T2DM duration, triglyceride (TG), hypertension history, high-density lipoprotein cholesterol (HDL-C), glycosylated haemoglobin (HbA1c), serum creatinine (Scr), homeostasis model assessment of insulin resistance (HOMA-IR), urine acid (UA), SFRP-5 HMW-ADP, and VEGF165 were significant between control and DR groups (P&lt;0.05). HMW-ADP, VEGF165 and SFRP-5 had predictive values for DR (AUC&gt;0.7), and the predictive efficiency of their combination was highest. The duration of T2DM, Scr, UA and VEGF165 were independent risk factors for DR, while HMW-ADP and SFRP-5 were protective factors (P&lt;0.05). Preferable discrimination and accuracy together with clinical applicability were obtained for the nomogram prediction model. Conclusions: The three indicators as a whole have a high predictive value for DR, as potential indicators for the clinical screening of high-risk groups.

Assessment of Serum Level of High-Molecular-Weight Adiponectin (HMW-APN) in Rheumatoid arthritis Patients and Its Correlation with the Disease Activity

Assessment of Serum Level of High-Molecular-Weight Adiponectin (HMW-APN) in Rheumatoid arthritis Patients and Its Correlation with the Disease Activity

Correlations of high molecular weight adiponectin, tumor necrosis factor-alpha and vascular endothelial growth factors with occurrence of colonic polyps in the prediabetic population.

We aimed to explore the correlations of high molecular weight adiponectin (HMW-ADP), tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factors (VEGFs) with the occurrence of colonic polyps in the prediabetic population. Two hundred patients with prediabetes were enrolled, and their clinical data were retrospectively analyzed. They were divided into group A (75 patients with colonic polyps) and group B (125 patients without colonic polyps). Eighty patients with normal glucose tolerance in the same period were divided into group C (32 patients with normal glucose tolerance and colonic polyps) and group D (48 patients with normal glucose tolerance but no colonic polyps). The correlations of serum HMW-ADP, TNF-α and VEGF levels with plasma glucose and insulin levels were explored by Pearson's analysis. The factors influencing the occurrence of colonic polyps were determined by logistic regression analysis. Serum HMW-ADP was negatively correlated with TNF-α, VEGFs, FPG, 2hPG, FI and HOMA-IR (r<0, P<0.05), whereas serum TNF-α and VEGFs were positively correlated with FPG, 2hPG, FI and HOMA-IR (r>0, P<0.05). Age, body mass index, waist-to-hip ratio, history of smoking, history of drinking, family history of colon cancer, TNF-α and VEGF were independent risk factors [odds ratio (OR)>1, P<0.05], and HMW-ADP was a protective factor (OR<1, P<0.05). The areas under the curves of serum HMW-ADP, TNF-α, VEGFs and their combination for predicting the occurrence of colonic polyps were 0.899, 0.787, 0.908 and 0.922, respectively. The combination of HMW-ADP, TNF-α and VEGFs can effectively predict the occurrence of colonic polyps in prediabetic patients.

Serum IL-23 significantly decreased in obese patients with psoriatic arthritis six months after a structured weight loss intervention

IntroductionPatients with psoriatic arthritis (PsA) are frequently obese. We have previously shown decreased disease activity in patients with PsA with a body mass index (BMI) ≥ 33 kg/m2 following weight loss treatment with Very Low Energy Diet (VLED), resulting in a median weight loss of 18.6% at six months (M6) after baseline (BL). In this study we assessed the effects of VLED on cytokines and adipokines at M6 in the same patients with PsA and controls (matched on sex, age and weight).MethodsVLED (640 kcal/day) during 12 or 16 weeks, depending on BL BMI < 40 or ≥ 40 kg/m2, was taken and followed by an energy-restricted diet. Cytokines and adipokines were measured with Magnetic Luminex Assays at BL and M6.ResultsSerum interleukin (IL)-23, (median (interquartile range) 0.40 (0.17–0.54) ng/mL vs. 0.18 (0.10–0.30) ng/mL, p < 0.001) and leptin (26.28 (14.35–48.73) ng/mL vs. 9.25 (4.40–16.24) ng/mL, p < 0.001) was significantly decreased in patients with PsA. Serum total (tot)-adiponectin and high molecular weight (HMW) adiponectin increased significantly. Similar findings were found in controls. Also, in patients with PsA, ∆BMI was positively correlated with ∆IL-23 (rS = 0.671, p < 0.001). In addition, significant positive correlations were found between ΔBMI and ΔDisease Activity Score (DAS28CRP), ΔCRP, Δtumor necrosis factor (TNF)-α, ΔIL-13, ∆IL-17 and Δleptin, and negative correlations between ΔBMI and Δtot-adiponectin.ConclusionsWeight loss was associated with decreased levels of leptin and cytokines, in particular IL-23. These findings may partly explain the anti-inflammatory effect of weight reduction in PsA.Trial registrationClinicalTrials.gov identifier: NCT02917434, registered on September 21, 2016, retrospectively registered.

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.

1203-P: Elevated HOMA-IR and IL-6 in Pregnant Women with Metabolic-Dysfunction–Associated Fatty Liver Disease and Gestational Diabetes Mellitus

Background: It is uncertain whether biomarkers differ in singleton pregnant women with metabolic dysfunction-associated fatty liver disease (MAFLD) and gestational diabetes mellitus (GDM). Methods: A prospective cohort study was conducted. A FibroScan® was performed between 10-24 weeks. A controlled attenuation parameter score ≥233.5dB/m indicated MAFLD. GDM was diagnosed with IADPSG criteria. Between 24-30 weeks, fasting blood was collected to determine serum levels of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), fibroblast growth factor 21 (FGF-21), high molecular weight adiponectin (HMW-APN), glucose and insulin. HOMA-IR was calculated: [insulin (mU/L) × glucose (mmol/L)]/22.5. Four groups of control (no GDM/MAFLD), MAFLD only, GDM only, MAFLD &amp; GDM were formed. Biomarkers were analyzed by general linear models after log transformation, adjusted for age, body mass index, ethnicity and nulliparity. Results: Of 120 women, 47 were control, 37 MAFLD only, 14 GDM only and 22 MAFLD &amp; GDM. Compared to controls, MAFLD &amp; GDM had 1.8-fold higher HOMA-IR and IL-6, significantly elevated over GDM only and MAFLD only (Table 1). No significant differences in TNF-α, FGF-21 or HMW-APN occurred (Table 1). Conclusions: Significantly elevated HOMA-IR and IL-6 in pregnant women with MAFLD &amp; GDM suggests a more insulin resistant and inflammatory phenotype. Disclosure T.Y.L.Chai: None. D.Pasupathy: None. J.George: None. N.Cheung: None. Funding Diabetes Australia Research Program (Y21GCHEW)

Tumor necrosis factor-α reduces adiponectin production by decreasing transcriptional activity of peroxisome proliferator-activated receptor-γ in calf adipocytes

Adiponectin (encoded by ADIPOQ) is an adipokine that orchestrates energy homeostasis by modulating glucose and fatty acid metabolism in peripheral tissues. During the periparturient period, dairy cows often develop adipose tissue inflammation and decreased plasma adiponectin levels. Proinflammatory cytokine tumor necrosis factor-α (TNF-α) plays a pivotal role in regulating the endocrine functions of adipocytes, but whether it affects adiponectin production in calf adipocytes remains obscure. Thus, the present study aimed to determine whether TNF-α could affect adiponectin production in calf adipocytes and to identify the underlying mechanism. Adipocytes isolated from Holstein calves were differentiated and used for (1) BODIPY493/503 staining; (2) treatment with 0.1 ng/mL TNF-α for different times (0, 8, 16, 24, or 48 h); (3) transfection with peroxisome proliferator-activated receptor-γ (PPARG) small interfering RNA for 48 h followed by treatment with or without 0.1 ng/mL TNF-α for 24 h; and (4) overexpression of PPARG for 48 h followed by treatment with or without 0.1 ng/mL TNF-α for 24 h. After differentiation, obvious lipid droplets and secretion of adiponectin were observed in adipocytes. Treatment with TNF-α did not alter mRNA abundance of ADIPOQ but reduced the total and high molecular weight (HMW) adiponectin content in the supernatant of adipocytes. Quantification of mRNA abundance of endoplasmic reticulum (ER)/Golgi resident chaperones involved in adiponectin assembly revealed that ER protein 44 (ERP44), ER oxidoreductase 1α (ERO1A), and disulfide bond-forming oxidoreductase A-like protein (GSTK1) were downregulated in TNF-α-treated adipocytes, while 78-kDa glucose-regulated protein and Golgi-localizing γ-adaptin ear homology domain ARF binding protein-1 were unaltered. Moreover, TNF-α diminished nuclear translocation of PPARγ and downregulated mRNA abundance of PPARG and its downstream target gene fatty acid synthase, suggesting that TNF-α suppressed the transcriptional activity of PPARγ. In the absence of TNF-α, overexpression of PPARG enhanced the total and HMW adiponectin content in supernatant and upregulated the mRNA abundance of ADIPOQ, ERP44, ERO1A, and GSTK1 in adipocytes. However, knockdown of PPARG reduced the total and HMW adiponectin content in supernatant and downregulated the mRNA abundance of ADIPOQ, ERP44, ERO1A, and GSTK1 in adipocytes. In the presence of TNF-α, overexpression of PPARG decreased, while knockdown of PPARG further exacerbated TNF-α-induced reductions in total and HMW adiponectin secretion and gene expression of ERP44, ERO1A, and GSTK1. Overall, TNF-α reduces adiponectin assembly in the calf adipocyte, which may be partly mediated by attenuation of PPARγ transcriptional activity. Thus, locally elevated levels of TNF-α in adipose tissue may be one reason for the decrease in circulating adiponectin in periparturient dairy cows.

Associations between dietary inflammatory scores and biomarkers of inflammation in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Since the first version of the dietary inflammatory index (DII®) developed in the past decade, several other versions have been developed. However, to date no study has attempted to compare these versions with respect to their associations with biomarkers of inflammation. We aimed to investigate the relationship between four dietary inflammatory scores [DII, two energy-adjusted derivatives (E-DII and E-DIIr), and the Inflammatory Score of the Diet (ISD)], and circulating levels of several inflammatory markers and adipokines. This study included 17637 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with at least one marker of inflammation measured in blood. Associations between the four scores and C-reactive protein (CRP), interleukin (IL)6, IL10, IL1RA, tumor necrosis factor-α (TNFα), soluble tumor necrosis factor receptor-1 (sTNFR1), sTNFR2, leptin, soluble leptin receptor (sLeptin R), adiponectin, and High Molecular Weight (HMW) adiponectin were evaluated using multivariable linear regressions adjusted for potential confounders. Positive associations were observed between the four dietary inflammatory scores and levels of CRP, IL6, sTNFR1, sTNFR2 and leptin. However, only the DII and the ISD were positively associated with IL1RA levels and only the DII and the E-DIIr were positively associated with TNFα levels. The proportion of variance of each biomarker explained by the scores was lower than 2%, which was equivalent to the variance explained by smoking status but much lower than that explained by body mass index. Our results suggest that the four dietary inflammatory scores were associated with some biomarkers of inflammation and could be used to assess the inflammatory potential of diet in European adults but are not sufficient to capture the inflammatory status of an individual. These findings can help to better understand the inflammatory potential of diet, but they need to be replicated in studies with repeated dietary measurements.

APN Expression in Serum and Corpus Luteum: Regulation of Luteal Steroidogenesis Is Possibly Dependent on the AdipoR2/AMPK Pathway in Goats

Adiponectin (APN) is an essential adipokine for a variety of reproductive processes. To investigate the role of APN in goat corpora lutea (CLs), CLs and sera from different luteal phases were collected for analysis. The results showed that the APN structure and content had no significant divergence in different luteal phases both in CLs and sera; however, high molecular weight APN was dominant in serum, while low molecular weight APN was more present in CLs. The luteal expression of both AdipoR1/2 and T-cadherin (T-Ca) increased on D11 and 17. APN and its receptors (AdipoR1/2 and T-Ca) were mainly expressed in goat luteal steroidogenic cells. The steroidogenesis and APN structure in pregnant CLs had a similar model as in the mid-cycle CLs. To further explore the effects and mechanisms of APN in CLs, steroidogenic cells from pregnant CLs were isolated to detect the AMPK-mediated pathway by the activation of APN (AdipoRon) and knockdown of APN receptors. The results revealed that P-AMPK in goat luteal cells increased after incubation with APN (1 μg/mL) or AdipoRon (25 μM) for 1 h, and progesterone (P4) and steroidogenic proteins levels (STAR/CYP11A1/HSD3B) decreased after 24 h. APN did not affect the steroidogenic protein expression when cells were pretreated with Compound C or SiAMPK. APN increased P-AMPK and reduced the CYP11A1 expression and P4 levels when cells were pretreated with SiAdipoR1 or SiT-Ca, while APN failed to affect P-AMPK, the CYP11A1 expression or the P4 levels when pretreated with SiAdipoR2. Therefore, the different structural forms of APN in CLs and sera may possess distinct functions; APN might regulate luteal steroidogenesis through AdipoR2 which is most likely dependent on AMPK.

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.

Docosahexaenoic acid supplementation in gestational diabetes mellitus and neonatal metabolic health biomarkers.

Gestational diabetes mellitus (GDM) "programs" an elevated risk of metabolic dysfunctional disorders in the offspring, and has been associated with elevated leptin and decreased adiponectin levels in cord blood. We sought to assess whether docosahexaenoic acid (DHA) supplementation in GDM affects neonatal metabolic health biomarkers especially leptin and adiponectin. In a randomized controlled trial, singleton pregnant women with de novo diagnosis of GDM at 24-28 weeks of gestation were randomized to dietary supplementation of 500 mg DHA per day (intervention, n = 30) until delivery or standard care (control, n = 38). The primary outcomes were cord blood leptin and total adiponectin concentrations. Secondary outcomes included high-molecular-weight (HMW) adiponectin and insulin-like growth factor-1 (IGF-1) concentrations in cord blood, maternal glycemic control post-intervention and birth weight (z score). In parallel, 38 euglycemic pregnant women were recruited for comparisons of cord blood biomarkers. There were no significant differences in cord serum leptin, total and HMW adiponectin and IGF-1 concentrations between DHA supplementation and control groups (all p > 0.05). Maternal fasting and 2-h postprandial blood glucose levels at 12-16 weeks post-intervention were similar between the two groups. The newborns in the DHA group had higher birth weight z scores (p = 0.02). Cord blood total and HMW adiponectin concentrations were significantly lower in GDM vs. euglycemic pregnancies. Docosahexaenoic acid supplementation at 500 mg/day in GDM women did not affect neonatal metabolic biomarkers including leptin, adiponectin and IGF-1. The results are reassuring in light of the absence of influence on neonatal adipokines (leptin and adiponectin), and potential benefits to fetal growth and development. Clinicaltrials.gov, NCT03569501.

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).

High molecular weight adiponectin and DXA-derived abdominal subcutaneous adipose tissue may independently protect against type 2 diabetes regardless of body mass index

High molecular weight adiponectin and DXA-derived abdominal subcutaneous adipose tissue may independently protect against type 2 diabetes regardless of body mass index

Daily Folic Acid and/or Vitamin B12 Supplementation Between 6 and 30 Months of Age and Cardiometabolic Risk Markers After 6–7 Years: A Follow-Up of a Randomized Controlled Trial

BackgroundDeficiencies of vitamin B12 and folate are associated with elevated concentrations of metabolic markers related to CVDs. ObjectivesWe investigated the effect of supplementation of vitamin B12 with or without folic acid for 6 mo in early childhood on cardiometabolic risk markers after 6–7 y. MethodsThis is a follow-up study of a 2 × 2 factorial, double-blind, randomized controlled trial of vitamin B12 and/or folic acid supplementation in 6–30-mo-old children. The supplement contained 1.8 μg of vitamin B12, 150 μg of folic acid, or both, constituting >1 AI or recommended daily allowances for a period of 6 mo. Enrolled children were contacted again after 6 y (September 2016–November 2017), and plasma concentrations of tHcy, leptin, high molecular weight adiponectin, and total adiponectin were measured (N = 791). ResultsAt baseline, 32% of children had a deficiency of either vitamin B12 (<200 pmol/L) or folate (<7.5 nmol/L). Combined supplementation of vitamin B12 and folic acid resulted in 1.19 μmol/L (95% CI: 0.09; 2.30 μmol/L) lower tHcy concentration 6 y later compared to placebo. We also found that vitamin B12 supplementation was associated with a lower leptin–adiponectin ratio in subgroups based on their nutritional status. ConclusionsSupplementation with vitamin B12 and folic acid in early childhood was associated with a decrease in plasma tHcy concentrations after 6 y. The results of our study provide some evidence of persistent beneficial metabolic effects of vitamin B12 and folic acid supplementation in impoverished populations.The original trial was registered at www.clinicaltrials.gov as NCT00717730, and the follow-up study at www.ctri.nic.in as CTRI/2016/11/007494.