Lower Adiponectin Levels Research Articles

Adiponectin Is Related to Cardiovascular Risk in Severe Mental Illness Independent of Antipsychotic Treatment.

Background: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) associated with elevated cardiovascular disease (CVD) risk, including obesity. Leptin and adiponectin are secreted by adipose tissue, with pro- and anti-inflammatory properties, respectively. The second generation antipsychotics (AP) olanzapine, clozapine, and quetiapine have been associated with high leptin levels in SMI. However, the link between inflammatory dysregulation of leptin and adiponectin and CVD risk in SMI, and how this risk is influenced by body mass and AP medication, is still not completely understood. We investigated herein if leptin, adiponectin or their ratio (L/A ratio) could predict increased CVD risk in SCZ, BD, and in subgroups according to use of antipsychotic (AP) treatment, independent of other cardio-metabolic risk factors.Methods: We measured fasting plasma levels of leptin and adiponectin, and calculated the L/A ratio in n = 1,092 patients with SCZ and BD, in subgroups according to AP treatment, and in n = 176 healthy controls (HC). Differences in the levels of adipokines and L/A between groups were examined in multivariate analysis of covariance, and the correlations between adipokines and body mass index (BMI) with linear regression. CVD risk was defined by total cholesterol/high-density lipoprotein (TC/HDL) and triglyceride/HDL (TG/HDL) ratios. The adipokines and L/A ratios ability to discriminate individuals with TG/HDL and TC/HDL ratios above threshold levels was explored by ROC analysis, and we investigated the possible influence of other cardio-metabolic risk factors on the association in logistic regression analyses.Results: We observed higher leptin levels and L/A ratios in SMI compared with HC but found no differences in adiponectin. Both adipokines were highly correlated with BMI. The low adiponectin levels showed a fair discrimination in ROC analysis of individuals with CVD risk, with AUC between 0.7 and 0.8 for both TC/HDL and TG/HDL, in all groups examined regardless of diagnosis or AP treatment. Adiponectin remained significantly associated with an elevated TC/HDL and TG/HDL ratio in SMI, also after further adjustment with other cardio-metabolic risk factors.Conclusions: Adiponectin is not dysregulated in SMI but is associated with CVD risk regardless of AP treatment regime.

The associations of leptin and adiponectin with the metabolic syndrome in an Indonesian and a Dutch population

Background and aimsAt the same BMI, Asian populations develop cardiometabolic complications earlier than Western populations. We hypothesized that a different secretion of the adipocyte-derived hormones leptin and adiponectin plays a role and investigated the associations of the two hormones with the metabolic syndrome (MetS) in an Indonesian and a Dutch population. Methods and resultsWe performed cross-sectional analyses of the Netherlands Epidemiology of Obesity Study (n = 6602) and the SUGAR Scientific Programme Indonesia–Netherlands Study (n = 1461). We examined sex-stratified associations of leptin and adiponectin with MetS, using multivariate logistic regression including adjustment for total body fat. The mean (SD) leptin (mcg/L) were 4.7 (6.0) in Indonesian men, 18.6 (12.0) in Indonesian women, 9.1 (7.7) in Dutch men, and 23.4 (17.4) in Dutch women. The mean (SD) adiponectin (mg/L) were 5.7 (5.4), 7.5 (7.1), 6.6 (3.3), and 11.3 (4.9), respectively. Within the same BMI category, leptin concentrations were similar in the two populations, whereas adiponectin was lower in the Indonesian population. Per SD of leptin, adjusted prevalence odds ratios (ORs, 95%CI) of MetS were 0.9 (0.6–1.2) in Indonesian men, 1.1 (0.9–1.4) in Indonesian women, 2.2 (1.6–2.8) in Dutch men, and 1.2 (1.0–1.5) in Dutch women. Per SD of adiponectin, the ORs were 0.9 (0.7–1.2), 0.8 (0.7–1.0), 0.6 (0.6–0.8), and 0.4 (0.4–0.5), respectively. ConclusionsDespite lower adiponectin levels, adiponectin was not related to the MetS in the Indonesian population and can not explain their increased cardiometabolic risk at the same BMI.

Abstract P217: Associations Of Adipokine Levels With The Prevalence And Extent Of Valvular And Thoracic Aortic Calcification: The Multi-ethnic Study Of Atherosclerosis

Introduction: Extra-coronary calcification (ECC), a marker of systemic atherosclerosis, is an independent risk factor for incident cardiovascular disease (CVD). Adipokines participate in many cardiometabolic pathways and may mediate the effect of obesity on atherosclerosis. However, the relationship of adipokines with ECC is not well established. We hypothesized that higher leptin and resistin levels and lower adiponectin levels would be associated with a greater extent of ECC. Methods: We performed a cross-sectional analysis of 1,955 community dwelling adults free of clinical CVD in the MESA cohort. Serum adipokine levels and a cardiac CT scan were obtained at exam 2 or 3 (randomly assigned). ECC was quantified by Agatston score and included calcification of the mitral annulus (MAC), aortic valve (AVC), ascending thoracic aorta (ATAC) and descending thoracic aorta (DTAC). We used multivariable regression to evaluate the associations between leptin, resistin and adiponectin (per 1 SD of log transformed adipokine) with the prevalence and extent of ECC. Results: The mean age of participants was 62±10 years; 50% were women, 40% white, 13% Chinese, 21% Black and 26% Hispanic. In a model adjusted for demographics, we found 1) adiponectin was inversely associated with AVC prevalence and extent; 2) leptin was positively associated with MAC prevalence and extent; and 3) resistin was positively associated with ATAC prevalence and extent and with DTAC prevalence. After full adjustment for BMI and other CVD risk factors ( Table ), adiponectin remained inversely associated with AVC prevalence, and resistin remained associated with greater ATAC prevalence and extent. Leptin was not associated with measures of ECC after full adjustment. No adipokine was associated with MAC or DTAC after full adjustment. Conclusion: In this diverse cohort free from clinical CVD, we found significant associations between selected adipokines and specific markers of ECC. Adipokines may play a role in the development of systemic atherosclerosis.

Low serum adiponectin level is associated with better physical health-related quality of life in chronic kidney disease

Hyperadiponectemia is paradoxically associated with renal disease progression and mortality in chronic kidney disease (CKD). Its association with health-related quality of life (HR-QOL) is unknown. This study aimed to verify the association between adiponectin and HR-QOL in Korean pre-dialysis CKD cohort. This cross-sectional study analyzed 1551 pre-dialysis CKD patients from KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into three tertiles (T1–T3) according to adiponectin levels. HR-QOL was assessed using SF-36. High physical component summary (PCS) and mental component summary (MCS) were defined as highest quartile of each score. Multivariate logistic regression was used to analyze odds ratio (OR) and 95% confidence interval (CI) for high PCS and MCS. Prevalence of high PCS were 33.3%, 27.5%, and 17.0% and that of high MCS were 31.7%, 24.8%, and 21.3% for T1, T2, and T3 (both p for trend < 0.001). The adjusted OR [95% CI] of T1 and T2 in reference to T3 were 1.56 [1.09–2.23] and 1.19 [0.85–1.68] for high PCS and 1.19 [0.85–1.68] and 0.94 [0.68–1.29] for high MCS. Serum adiponectin level was inversely associated with physical HR-QOL in Korean pre-dialysis CKD patients. This relationship was independent of various cardiovascular risk factors.

Secondary data analysis investigating effects of marine omega-3 fatty acids on circulating levels of leptin and adiponectin in older adults

BackgroundHigher leptin and lower adiponectin levels have been linked to progressing systemic inflammation and diseases of aging. Among older adults with obesity and an inflammatory conditions, we quantified effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on leptin, adiponectin, and the leptin-to-adiponectin ratio (LAR). We also examined associations among adipokine and cytokine levels. MethodsUsing a randomized, double-blind, placebo-controlled design, participants (mean age 61.3 ± 2.1) received 1.5 g EPA + 1.0 g DHA (n = 14) or mineral oil (n = 18) daily. Plasma adipokine and cytokine levels were quantified by electrochemiluminescence at all study intervals. ResultsWhile no between-group differences were detected, there was a reduction in the LAR (by 23%, p=.065) between weeks 4 and 8 among the EPA+DHA group. Adiponectin levels were negatively associated with IL-1β levels at week 4 (p=.02) and TNF-α levels at week 8 (p=.03). ConclusionPotential benefits of EPA+DHA supplementation among aging populations warrant further study.

Association of plasma adiponectin with tumor infiltrating lymphocytes and survival in patients with stage III colon cancer (NCCTG N0147; Alliance).

3591 Background: Adiponectin is a peptide hormone exclusively secreted by adipocytes that plays a role in immune regulation and in the host inflammatory response to cancer. We examined postsurgical adiponectin levels in relationship to tumor infiltrating lymphocytes (TILs), clinicopathological features, vitamin D status, and patient survival in participants in a phase 3 trial of adjuvant chemotherapy. Methods: Plasma adiponectin and 25-hydroxyvitamin D [25(OH)D] were analyzed by radioimmunoassay in 600 patients with stage III colon carcinoma who received adjuvant FOLFOX +/- cetuximab. TIL densities were determined at light microscopy in routine histopathological sections. The associations between adiponectin and 25(OH)D, TILs, other factors were evaluated by Fisher’s Exact, Chi-squared, t-test, and Kruskal-Wallis tests where appropriate. The association between adiponectin or 25(OH)D with disease-free survival (DFS), time to recurrence (TTR) and overall survival (OS) were evaluated by multivariable Cox regression, adjusting for body mass index (BMI), race, T, N stage, performance status, tumor location, TILs, BRAF/KRAS, and mismatch repair status. Results: A statistically significant and inverse association between adiponectin level and BMI was observed with lower levels found with obesity (BMI &gt; 30 kg/m2) [p &lt; 0.001]. The level of adiponectin was significantly lower in men vs women (p &lt; 0.001), in blacks vs whites or Asians (p &lt; 0.032), and in patients with fewer regional lymph node metastases (N1 vs N2 stage, p = 0.011). A significantly lower level of adiponectin was found in patients whose tumors had high vs low TIL densities (p = 0.040), but was unrelated to 25(OH)D. Insufficiency of 25(OH)D ( &lt; 30 ng/ml) was detected in 291 (49%) of patients and was not associated with TILs. By multivariable analysis, adiponectin was not associated significantly with patient DFS (HRadj= 0.98, 95% CI 0.74-1.29, padj= 0.88) nor with OS nor time-to-recurrence (TTR). TIL densities were significantly prognostic, but 25(OH)D was not (DFS: HRadj= 1.12, 95% CI 0.85-1.47, padj= 0.44). No significant interaction was observed for adiponectin with TILs for the association with DFS. Conclusions: Lower adiponectin levels were associated with significantly increased TIL densities in colon cancers, indicating an enhanced anti-tumor immune response. In contrast to TILs, adiponectin was not independently associated with patient outcome. Nearly one-half of stage III patients were vitamin D insufficient, although 25(OH)D was not prognostic.

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...

Galangin Resolves Cardiometabolic Disorders through Modulation of AdipoR1, COX-2, and NF-κB Expression in Rats Fed a High-Fat Diet.

Galangin is a natural flavonoid. In this study, we evaluated whether galangin could alleviate signs of metabolic syndrome (MS) and cardiac abnormalities in rats receiving a high-fat (HF) diet. Male Sprague–Dawley rats were given an HF diet plus 15% fructose for four months, and they were fed with galangin (25 or 50 mg/kg), metformin (100 mg/kg), or a vehicle for the last four weeks. The MS rats exhibited signs of MS, hypertrophy of adipocytes, impaired liver function, and cardiac dysfunction and remodeling. These abnormalities were alleviated by galangin (p < 0.05). Interleukin-6 and tumor necrosis factor-α concentrations and expression were high in the plasma and cardiac tissue in the MS rats, and these markers were suppressed by galangin (p < 0.05). These treatments also alleviated the low levels of adiponectin and oxidative stress induced by an HF diet in rats. The downregulation of adiponectin receptor 1 (AdipoR1) and cyclooxygenase-2 (COX-2) and the upregulation of nuclear factor kappa B (NF-κB) expression were recovered in the galangin-treated groups. Metformin produced similar effects to galangin. In conclusion, galangin reduced cardiometabolic disorders in MS rats. These effects might be linked to the suppression of inflammation and oxidative stress and the restoration of AdipoR1, COX-2, and NF-κB expression.

Cancer Progress and Priorities: Breast Cancer.

Breast cancer is the most commonly diagnosed invasive cancer among women both globally and within the United States and the number one cause of cancer-related deaths among women globally ([1, 2][1]). Less than 1% of diagnosed breast cancers occur in men ([2][2]) and, therefore, male breast cancer is

Hypoadiponectinemia is associated with aortic stiffness in nondialysis diabetic patients with stage 3-5 chronic kidney disease.

Albuminuria and serum adiponectin levels are factors that have been associated with the development of cardiovascular disease in patients with diabetes mellitus. Here we investigated the relationship between serum adiponectin levels and aortic stiffness in nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease. Fasting blood samples were obtained from 80 nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease. Carotid-femoral pulse wave velocity (cfPWV) was measured using applanation tonometry; cfPWV values of >10 m/s were defined as aortic stiffness. Serum adiponectin levels were determined by enzyme immunoassay. Forty-two patients (52.5%) with nondialysis diabetic kidney disease were diagnosed with aortic stiffness. The patients in this group were older (p = 0.011), had higher systolic blood pressure (p = 0.002) and urine albumin-to-creatinine ratios (p = 0.013), included fewer females (p = 0.024), and had lower serum adiponectin (p = 0.001) levels than those in the control group. Multivariable logistic regression analysis revealed that serum adiponectin was independently associated with aortic stiffness (odds ratio = 0.930, 95% confidence interval: 0.884-0.978, p = 0.005) and also positively correlated with cfPWV values by multivariable linear regression (β = -0.309, p = 0.002) in nondialysis diabetic kidney disease patients. The results suggested that serum adiponectin levels could be used to predict aortic stiffness in nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease.

Adipokines and Subclinical Cardiovascular Disease in Post-Menopausal Women: Study of Women's Health Across the Nation.

BackgroundThe menopausal transition is characterized by increased cardiovascular risk, weight gain, and increased adiposity for many women. The adipose‐derived secretory proteins adiponectin and leptin are associated with insulin resistance, metabolic syndrome, and cardiovascular disease but their role in subclinical atherosclerotic disease is unclear. This cross‐sectional study evaluated the associations of adiponectin and leptin with carotid artery intima‐media thickness, adventitial diameter, presence of carotid plaques, and brachial‐ankle pulse wave velocity (baPWV) in women aged 54 to 65 years.Methods and ResultsParticipants were 1399 women from SWAN (Study of Women's Health Across the Nation), a community‐based study of women transitioning through menopause. Carotid ultrasound and baPWV measures were obtained at SWAN follow‐up visits 12 or 13, when 97% of participants were post‐menopausal. Adipokines were assayed from serum specimens obtained concurrently at these visits. Linear and logistic regression models were used to evaluate adiponectin or leptin, both log‐transformed attributable to skewness, in relationship to carotid artery intima‐media thickness, adventitial diameter, baPWV, and presence of carotid plaque. Covariates included age, race, study site, smoking, alcohol use, obesity, cardiovascular disease risk factors, and menopausal status. Lower levels of adiponectin were related to greater carotid artery intima‐media thickness, wider adventitial diameter, and faster baPWV; associations were attenuated after adjusting for cardiovascular disease risk factors. Higher levels of leptin were associated with greater carotid artery intima‐media thickness and wider adventitial diameter in minimally and fully adjusted models, and contrary to expectation, with slower baPWV, particularly among women with diabetes mellitus or obesity.ConclusionsAdiponectin and leptin are 2 important inflammatory pathways that may contribute to adverse subclinical cardiovascular disease risk profiles in women at midlife.

Adipocyte and steroidogenic cell cross-talk in polycystic ovary syndrome.

Metabolic and endocrine alterations in women with polycystic ovary syndrome (PCOS) affect adipose tissue mass and distribution. PCOS is characterised by hyperandrogenism, obesity and adipocyte dysfunction. Hyperandrogenism in PCOS drives dysfunctional adipocyte secretion of potentially harmful adipocytokines. Glucocorticoids and sex-steroids modulate adipocyte development and function. For their part, adipocyte products interact with adrenal and ovarian steroidogenic cells. Currently, the relationship between adipocyte and steroidogenic cells is not clear, and for these reasons, it is important to elucidate the interrelationship between these cells in women with and without PCOS. This comprehensive review aims to assess current knowledge regarding the interrelationship between adipocytes and adrenal and ovarian steroidogenic cells in animal models and humans with or without PCOS. We searched for articles published in English and Portuguese in PubMed. Keywords were as follows: polycystic ovary syndrome, steroidogenesis, adrenal glands, theca cells, granulosa cells, adipocytes, adipocytokines, obesity, enzyme activation, and cytochrome P450 enzymes. We expanded the search into the references from the retrieved articles. Glucocorticoids and sex-steroids modulate adipocyte differentiation and function. Dysfunctional adipocyte products play important roles in the metabolic and endocrine pathways in animals and women with PCOS. Most adipokines participate in the regulation of the hypothalamic-pituitary-adrenal and ovarian axes. In animal models of PCOS, hyperinsulinemia and poor fertility are common; various adipokines modulate ovarian steroidogenesis, depending on the species. Women with PCOS secrete unbalanced levels of adipocyte products, characterised by higher levels of leptin and lower levels of adiponectin. Leptin expression positively correlates with body mass index, waist/hip ratio and levels of total cholesterol, triglyceride, luteinising hormone, oestradiol and androgens. Leptin inhibits the production of oestradiol and, in granulosa cells, may modulate 17-hydroxylase and aromatase enzyme activities. Adiponectin levels negatively correlate with fat mass, body mass index, waist-hip ratio, glucose, insulin and triglycerides, and decrease androgen production by altering expression of luteinising hormone receptor, steroidogenic acute regulatory protein, cholesterol-side-chain cleavage enzyme and 17-hydroxylase. Resistin expression positively correlates with body mass index and testosterone, and promotes the expression of 17-hydroxylase enzyme in theca cells. The potential benefits of adipokines in the treatment of women with PCOS require more investigation. The current data regarding the relationship between adipocyte products and steroidogenic cells are conflicting in animals and humans. Polycystic ovary syndrome is an excellent model to investigate the interrelationship among adipocyte and steroidogenic cells. Women with PCOS manifest some pathological conditions associated with hyperandrogenism and adipocyte products. In animals, cross-talk between cells may vary according to species, and the current review suggests opportunities to test new medications to prevent or even reverse several harmful sequelae of PCOS in humans. Further studies are required to investigate the possible therapeutic application of adipokines in women with obese and non-obese PCOS. Meanwhile, when appropriate, metformin use alone, or associated with flutamide, may be considered for therapeutic purposes.

Effects of Obesity on Airway and Systemic Inflammation in Asthmatic Children

Background: Obese asthma is a complex syndrome with certain phenotypes that differ in children and adults. There is no clear evidence regarding the presence of additive or synergistic pathological interaction between obesity and asthma in children. Objectives: Our aim was to demonstrate the interaction of obesity and asthma in children in terms of airway and systemic inflammation by a controlled observational study. Methods: Four groups were formed: asthma obese (AO), asthma nonobese (ANO), non-AO (NAO), nonasthma nonobese (NANO). Spirometry test, fractional exhaled nitric oxide (FeNO) test, skin prick test, serum inflammatory biomarkers (C-reactive protein, C3, C4, adiponectin, leptin, resistin, periostin, YKL-40, Type 1, and Type 2 cytokines) were conducted and evaluated in all participants. Sputum inflammatory cells (sputum eosinophils and neutrophils) were evaluated in patients who could produce induced sputum and obesity-asthma interactions were determined. Results: A total of 153 participants aged 6–18 years were included in the study, including the AO group (n = 46), the ANO group (n = 45), the NAO group (n = 30), and the NANO group (n = 32). IL-4 (p < 0.001), IL-5 (p < 0.001), IL-13 (p < 0.001), resistin (p < 0.001), and YKL-40 (p < 0.001) levels were higher in patients with asthma independent of obesity. The lowest adiponectin level was found in the AO group and obesity-asthma interaction was detected (p < 0.001). Sputum eosinophilia (p < 0.01), sputum neutrophilia (p < 0.01), and FeNO levels (p = 0.07) were higher in asthmatic patients independent of obesity. In the group with paucigranulocytic inflammation, resistin and YKL-40 levels were significantly lower than in the group without paucigranulocytic inflammation (p < 0.01). Conclusion: No interaction was found between obesity and asthma in terms of airway inflammation. Interaction between obesity and asthma was shown in terms of adiponectin level and resistin/adiponectin and leptin/adiponectin ratios. It was found that serum YKL-40 and resistin levels could be associated with airway inflammation.

The Relationship Between Adiponectin Serum Level and Coronary Artery Disease in Type 2 Diabetic Patients

Adiponectin is an adipocytokine that has a higher serum level in healthy people. In type 2 diabetes, insulin resistance, hypertension, MI, and dyslipidemia, the serum level of adiponectin is lower than 4 µg/mL. Adiponectin is proved to have a protective role against atherosclerotic changes where its low serum levels in type 2 diabetes can lead to the progression of atherosclerotic lesions. In this study, we aimed to survey the possible effects of adiponectin in the development of coronary artery disease in type 2 diabetics. Thirty diabetic cases with coronary artery disease, 30 diabetic cases without known coronary artery disease, and a group of 30 healthy volunteers, all of them were between 18-65-year-old, were entered ourstudy. We gathered demographic data by performing a physical examination followed by filling a checklist and a set of laboratory tests. All the groups were sex and age-matched (P=0.284 and P=0.163 respectively). CAD group had the lowest HBA1C (P&lt;0.001). Both LDL and HDL were also lower in the CAD group (P&lt;0.001). Adiponectin was also lower in the CAD group when compared to other groups (P&lt;0.008) or when compared with only normal diabetics (P&lt;0.002). We found a correlation between adiponectin and HDL (r=0.348, P=0.008), suggesting each unit of reduction in serum level of adiponectin could increase the chance of coronary artery disease by 38% in diabetics. In this study, we showed that the lower serum level of adiponectin is correlated with an increased risk of coronary artery disease in type 2 diabetics.

Associations of GDF-15 and GDF-15/adiponectin ratio with odds of type 2 diabetes in the Chinese population.

We elucidate the effect of Growth differentiation factor-15(GDF-15)/adiponectin ratio in improving the assessment value for odds of type 2 diabetes. Cross-sectional design. A total of 405 participants (135 patients with newly diagnosed type 2 diabetes, 135 age- and sex-matched participants with prediabetes, and 135 healthy controls) were collected from Guangzhou and Dongguan, China. The serum GDF-15 and adiponectin levels were measured by ELISA and latex-enhanced immunoturbidimetry. Logistic regression analysis and restricted cubic splines were used to evaluate the associations between diabetes and the indicators. The low level of adiponectin and high GDF-15/adiponectin ratio were significantly associated with increased odds of type 2 diabetes, but not for GDF-15. Three clusters were identified based on the K-means clustering analysis. Compared to the lowest quartiles of adiponectin, the OR and 95% CI of the highest adiponectin with type 2 diabetes was 0.24 (0.07-0.74, p trend = 0.004) after adjusting for sex, age, BMI, and DBP only in cluster 1. After adjusting for confounding factors, subjects with the highest GDF-15/adiponectin ratio quartiles had 3.9 times (OR = 3.85, 95% CI = 0.76-24.25) and 3.8 times (OR = 3.80, 95% CI = 1.02-14.68) higher odds of type 2 diabetes in cluster 2 and cluster 3, respectively. The association between the GDF-15/adiponectin ratio and type 2 diabetes was attenuated, but still remarkable (OR = 3.18, 95% CI = 1.11-10.18), in cluster 1. Higher GDF-15/adiponectin ratio is independently associated with increased odds of type 2 diabetes for all study populations, suggesting that the GDF-15/adiponectin ratio may be a better indicator of type 2 diabetes.

Relationship between adiponectin, TNF\u03b1, and SHBG in prepubertal children with obesity

BackgroundSex hormone-binding globulin (SHBG) levels are low in adult subjects with obesity when compared to normal-weight individuals. Obesity is associated with higher tumor necrosis factor alpha (TNFα) plasma levels and lower adiponectin levels. Moreover, we have recently elucidated the molecular mechanisms by which TNFα and adiponectin regulate hepatic SHBG production.AimThe main objective of this study was to assess if the adult associations between TNFα, adiponectin, and SHBG are present in prepubertal children.MethodsWe determined several morphometric and biochemical parameters in normal-weight (n=15) and obese prepubertal (n=51) children, as well as quantified plasma SHBG, TNFα receptor 1 (TNFα-R1), and adiponectin levels.ResultsOur results showed that prepubertal children with obesity had decreased plasma SHBG levels compared to normal-weight controls (67 nmol/L vs 172 nmol/L). Importantly, SHBG plasma levels correlated significantly (P < 0.05) with TNFα (negatively, ßstd= − 0.31) and adiponectin (positively, ßstd= 0.58) suggesting an important role of these two cytokines in determining plasma SHBG levels in prepubertal children.ConclusionsOur results suggest that plasma adiponectin levels may play a more important role than TNFα in influencing plasma SHBG levels in our prepubertal population with obesity.

Insulin resistance and high molecular weight adiponectin in obese and non-obese patients with Polycystic Ovarian Syndrome (PCOS)

BackgroundPolycystic ovarian syndrome (PCOS) is the most common endocrinopathy among young women. Insulin resistance is a key feature in the pathogenesis of PCOS; also high molecular weight adiponectin is a marker of insulin resistance. The aim of this study was to evaluate the insulin resistance, metabolic and androgenic profiles and high molecular weight adiponectin in obese and non-obese PCOS patients.MethodsIn this cross-sectional study in outpatient endocrinology clinics of Shiraz University of Medical Sciences, 80 women aged 17–43 years old with PCOS were enrolled. Biochemical and hormonal assay was done on fasting blood sample on the third day of follicular phase.ResultsThe individuals had a mean age of 28.39 ± 6.56 years, mean weight of 65.41 ± 12.59 Kg, mean BMI of 25.5 ± 4.9, and mean waist circumference of 88.0 ± 13.1 cm. Of all individuals 20% had frank insulin resistance with HOMA-IR > 3.8. Although the obese PCOS patients had lower levels of high molecular weight adiponectin (P = 0.03) than the normal weight PCOS individuals, the level of insulin and insulin resistance was not different in them (P = 0.13, 0.13). Patients with classic PCOS phenotype significantly had higher levels of insulin resistance and free androgen index (P < 0.001, 0.001). We found a significant correlation between the insulin level and free androgen index (correlation coefficient: 0.266 and P = 0.018) after adjusting for BMI.ConclusionThis cross-sectional study showed a high incidence of insulin resistance in PCOS patients independent of obesity, and determined BMI related lower level of high molecular weight adiponectin in obese PCOS individuals. More detailed studies are warranted for evaluation of insulin resistance and its pathophysiologic role in PCOS.

Association between carriers of the G allele of the + 45T> G variant of the ADIPOQ gene (rs 2241766) and the cardiometabolic profile in sickle cell trait

Aimsinvestigate the association between the +45T > G variant of the ADIPOQ gene and the metabolic syndrome (MS) in patients with sickle cell trait (SCT). 33 patients with SCT and 35 control group participated in the study. Lower levels of HDL and adiponectin were observed in patients with G allele and sickle cell trait. There were no differences between the prevalence of MS between the groups and there was no association between the +45T > G variant of the ADIPOQ gene and MS risk allele. Materials and methodsParticipants with and without sickle cell anemia answered a questionnaire, performed anthropometric and laboratory analyzes. They were genotyped for the +45T > G variant of the ADIPOQ gene and evaluated for the presence or absence of metabolic syndrome. The study was approved by the Research Ethics Committee of UNIPAMPA (RS/Brazil). Key findingsThe GG + TG genetic model, it was associated with lower levels of adiponectin and HDL cholesterol in the SCT group. There was no association between the other studied markers and MS. SignificanceFor the first time, an association was demonstrated between the G allele of the +45T > G variant of the ADIPOQ gene and a worse cardiometabolic profile (lower serum concentrations of adiponectin and HDL cholesterol) in patients with sickle cell trait.

Effect of Epidermal Growth Factor Treatment and Polychlorinated Biphenyl Exposure in a Dietary-Exposure Mouse Model of Steatohepatitis.

Background:Polychlorinated biphenyls (PCBs) are signaling disrupting chemicals that exacerbate nonalcoholic steatohepatitis (NASH) in mice. They are epidermal growth factor receptor (EGFR) inhibitors that enhance hepatic inflammation and fibrosis in mice.Objectives:This study tested the hypothesis that epidermal growth factor (EGF) administration can attenuate PCB-related NASH by increasing hepatic EGFR signaling in a mouse model.Methods:C57BL/6 male mice were fed a 42% milk fat diet and exposed to Aroclor 1260 () or vehicle for 12 wk. EGF () or vehicle were administered daily for 10 d starting at study week 10. Liver and metabolic phenotyping were performed. The EGF dose was selected based on results of an acute dose–finding study (30 min treatment of EGF at 0.2, 0.02, of via intraperitoneal injection). Hepatic phosphoproteomic analysis was performed using liver tissue from this acute study to understand EGFR’s role in liver physiology.Results:Markers of EGFR signaling were higher in EGF-treated mice. –exposed mice had lower hepatic free fatty acids, inflammation, and fibrosis relative to PCB-only exposed mice. EGF-treated mice had higher plasma lipids, with no improvement in hepatic steatosis, and an association with higher LXR target gene expression and de novo lipogenesis. EGF-treated mice showed more severe hyperglycemia associated with lower adiponectin levels and insulin sensitivity. EGF-treated mice had higher hepatic , NRF2, and AhR target gene expression but lower constitutive androstane receptor and farnesoid X receptor target gene expression. The hepatic EGF-sensitive phosphoproteome demonstrated a role for EGFR signaling in liver homeostasis.Discussion:These results validated EGFR inhibition as a causal mode of action for PCB-related hepatic inflammation and fibrosis in a mouse model of NASH. However, observed adverse effects may limit the clinical translation of EGF therapy. More data are required to better understand EGFR’s underinvestigated roles in liver and environmental health. https://doi.org/10.1289/EHP8222

Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles.

IntroductionMetabolic syndrome arises from abnormal adipose function accompanied by insulin resistance. As early factors reflecting/impacting lipid storage dysfunction of adipose tissues, we sought to determine adipokine levels in subcutaneous and visceral adipose tissues (SAT and VAT).Material and methodsGene and protein expression levels of leptin, adiponectin, and resistin were analysed in SAT and VAT of normal-weight and overweight/obese women, subclassified according to insulin resistance index, triglyceride, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels into metabolically healthy and “at risk” groups.ResultsCompared with normal-weight women, obese women had higher serum leptin levels (p < 0.05), as well as increased leptin gene and protein expression in VAT. Conversely, expression levels of leptin were lower in SAT of obese women, and minor in the SAT of “at risk” groups of women, compared with weight-matched healthy groups. In addition, lower adiponectin levels were detected in SAT of metabolically healthy obese women (p < 0.01), and lower in SAT and VAT (p < 0.05) of “at risk” obese women compared to healthy, obese women. Significant differences in resistin levels were only observed in obese women; resistin gene expression was higher in VAT and SAT of obese, compared to normal-weight women. However, higher gene expression was not consistent with protein expression of resistin.ConclusionsLow adiponectin in both examined adipose tissues and inappropriate leptin expression levels in SAT appear to be important characteristics of obesity-related metabolic syndrome. Intriguingly, this adipokine dysregulation is primary seen in SAT, suggesting that endocrine dysfunction in this abdominal depot may be an early risk sign of metabolic syndrome.