Lower Adiponectin Levels Research Articles

Peptide hormones and risk for future cardiovascular events among prediabetics: a 20-year follow-up in the OPERA study

Background: Prediabetes has proven to have many unfavourable impacts on the cardiovascular system.Methods: The OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study included 1045 middle-aged subjects followed from the years 1990–1993 to 2014. The focus was on peptide hormones.Results: Plasma resistin levels were higher among prediabetics (p = .001), particularly impaired glucose tolerance (IGT) (p < .001), but not impaired fasting glucose (IFG) patients than among normal glucose tolerance (NGT) or diabetes groups. Diabetics showed lower resistin levels than IGT subjects (p < .001). IGT or diabetes groups showed lower adiponectin and higher leptin levels compared to the NGT group (p < .001). The IFG group had the highest blood pressure and left ventricular mass index, even higher than the diabetic group. Diabetics had the highest, prediabetics (IFG + IGT) intermediate and NGT the lowest risk for CVD events during follow-up (p < .001). Among prediabetics, high plasma ghrelin was an independent predictor of CVD events (p < .05) in the Cox regression analysis although it did not significantly improve either classification or discrimination of the patients.Conclusions: Among glucose tolerance groups, patients with IGT had the highest resistin, but equally high leptin and low adiponectin levels as diabetics. Among prediabetics, ghrelin seems to predict independently cardiovascular events in the long term.KEY MESSAGEAmong glucose tolerance groups, patients with IGT had the highest resistin, but equally high leptin and low adiponectin levels as diabetics.Among prediabetics, ghrelin seems to predict independently cardiovascular events in the long term.

A non-obese, diet-induced animal model of nonalcoholic steatohepatitis in Wistar/ST rats compared to Sprague-Dawley rats

Summary Background Non-alcoholic steatohepatitis (NASH), a subtype of non-alcoholic fatty liver disease (NAFLD), is a potentially progressive liver disease that can lead to cirrhosis. Obesity increases the risk of NAFLD/NASH, but this disease can also be observed in non-obese individuals. Methods We investigated the metabolic and histopathological changes in 13 obesity-resistant Slc:Wistar/ST rats fed a high-fat and high-cholesterol (HFC) diet for 9 weeks, and also retrospectively compared the results of 41 Sprague-Dawley (SD) rats that were previously fed with the same protocol to the results of the Slc:Wistar/ST rats. Results Of the 13 Slc:Wistar/ST rats fed an HFC diet containing 1.25% or 2.5% cholesterol, 11 (84.6%) developed histologically proven NASH without obesity, an increased visceral fat volume, insulin resistance, histopatological severe lobular inflammation and severe hepatic fibrosis. The HFC diets significantly increased the levels of mRNA encoding collagen type I alpha 1 (COL1A1), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). The SD rats also developed NASH without obesity, an increased visceral fat volume and insulin resistance, but the metabolic and histopathological effects, such as lower serum adiponectin levels, higher serum leptin levels, histopatological severe lobular inflammation and hepatic fibrosis, seemed to be more pronounced in the SD rats than in the Slc:Wistar/ST rats. Conclusions These two rat models may reflect the human etiology of NASH that is influenced by dietary factors, and the obesity-resistant Slc:Wistar/ST rat model may be particularly useful for elucidating the pathophysiological mechanism of the so-called lean NASH.

A mathematical model of adiponectin resistance

Adiponectin is often associated with obesity. The obese body displays a significant decrease in adiponectin expression and plasma levels. Higher adiponectin also results in lower expression of pro-inflammatory cytokine TNF-α from adipose tissue. Low adiponectin levels show to exist significantly in the case of insulin resistance. Adiponectin levels are found to be significantly lower in people with type 2 diabetes. In this paper, we proposed a mathematical model of the adiponectin − adiponectin receptors framework, based on the assumption that the secretion of adiponectin is inversely proportional to fat mass. Here, we show that an increase in obesity or adiposity results in a decrease in the adiponectin plasma level, which contributes to the development of adiponectin resistance. In this model, we have used different parameters and their default values, to perform a simulation based on the model. Further, experimentally, the plasma adiponectin concentration is ( ≈ 0.015) significantly lowered in the diabetic group compared to the non-diabetic group. In this model, we have obtained the plasma adiponectin concentration level ( ≈ 0.014) in the simulation process. So this model is only differing from 1 × 10−3 significant digits. We have achieved the degree of accuracy of adiponectin resistance is 93.33%. Therefore, these advances offer novel insights into the mathematical approach.

Circadian rhythm abnormalities in patients with inflammatory bowel disease – association with adipokine profile

Background: The role of sleep disturbances in patients with inflammatory bowel disease (IBD) remained relatively unknown. The aim of this study was to identify the adipokine profile in the patients with IBD and its relationship with the circadian rhythm disorders.Methods: Prospective, observational cohort study was performed. In all the enrolled adult IBD patients, the disease activity was assessed by using Crohn’s Disease Activity Index (CDAI) for Crohn’s disease (CD) and Partial Mayo Score for ulcerative colitis (UC), respectively. All patients were also asked to respond to a questionnaire to define Pittsburgh Quality Sleep Index (PSQI). From all the enrolled patients, 15 mL venous blood was taken to determine adipokine levels and perform standard laboratory tests.Results: Sixty-five IBD patients were enrolled in our study: 30 with CD and 35 with UC. Poor sleep was noted in 69.2% patients with clinically active and in 7.7% patients with inactive disease (p = .0023). In the group of IBD patients with poor sleep, the significantly higher level of serum resistin (p = .0458), and lower level of serum adiponectin and leptin (p = .0215, p = .0201; respectively) were observed. In the IBD patients with exacerbation, the significantly higher level of serum resistin (p = .0396), significantly lower serum level of leptin (p = .0453) and tendency to lower serum level of adiponectin (p = .1214) were recorded.Conclusions: The relationship between circadian rhythm abnormalities and specific adipokine profile may show us a risk factor of developing inflammatory intestinal lesions in IBD patients. This knowledge may allow the treatment of sleep disturbances, body weight-control and dietary habits become new targets in IBD therapy.

A Novel Model of Diabetic Complications: Adipocyte Mitochondrial Dysfunction Triggers Massive β-Cell Hyperplasia.

Obesity-associated type 2 diabetes mellitus (T2DM) entails insulin resistance and loss of β-cell mass. Adipose tissue mitochondrial dysfunction is emerging as a key component in the etiology of T2DM. Identifying approaches to preserve mitochondrial function, adipose tissue integrity, and β-cell mass during obesity is a major challenge. Mitochondrial ferritin (FtMT) is a mitochondrial matrix protein that chelates iron. We sought to determine whether perturbation of adipocyte mitochondria influences energy metabolism during obesity. We used an adipocyte-specific doxycycline-inducible mouse model of FtMT overexpression (FtMT-Adip mice). During a dietary challenge, FtMT-Adip mice are leaner but exhibit glucose intolerance, low adiponectin levels, increased reactive oxygen species damage, and elevated GDF15 and FGF21 levels, indicating metabolically dysfunctional fat. Paradoxically, despite harboring highly dysfunctional fat, transgenic mice display massive β-cell hyperplasia, reflecting a beneficial mitochondria-induced fat-to-pancreas interorgan signaling axis. This identifies the unique and critical impact that adipocyte mitochondrial dysfunction has on increasing β-cell mass during obesity-related insulin resistance.

SUN-168 Low Serum Adiponectin Levels are Associated with Endothelial Dysfunction in Non-Dialysis Dependent Chronic Kidney Disease Patients

Cardiovascular disease, which mainly contributed from atherosclerosis, is the leading cause of death in patients with chronic kidney disease (CKD). Beyond the well-known traditional risk factors, endothelial dysfunction is closely associated with cardiovascular mortality and is highly prevalent in patients with CKD. Moreover, adipose tissue, which secreted various adipokines, was shown to play a critical role in the regulation of endothelial function. We aimed to evaluate the correlation of endothelial function with serum levels of adiponectin and leptin in patients with non-dialysis CKD. A total of 130 non-dialysis CKD patients, aged 65.4 ± 11.9 years, were recruited. Serum adiponectin levels were measured using a commercially available enzyme immunoassay kit. Endothelial function and vascular reactivity index (VRI) were measured using digital thermal monitoring test. In this study, VRI < 1.0, VRI 1.0–1.9, and VRI ≥ 2.0 were defined as poor, intermediate, and good vascular reactivity, respectively. Among them, 22 (16.9%) patients had poor VRI, who exhibited an elevated serum BUN (P = 0.037), decreased eGFR (P = 0.047) and serum adiponectin levels (P < 0.001). After multivariate adjustment in linear regression, serum BUN levels (β = -0.176, adjusted R2 change = 0.025; P = 0.021) and adiponectin levels (β = 0.487, adjusted R2 change = 0.256; P < 0.001) were independently associated with VRI values in non-dialysis CKD patients. Serum fasting adiponectin levels were positively associated with VRI values among non-dialysis CKD patients. Further studies are required to elucidate the relationship between endothelial function and adiponectin levels in non-dialysis CKD patients.

Interfering Role of ERα on Adiponectin Action in Breast Cancer.

Obesity is characterized by an excess of adipose tissue, due to adipocyte hypertrophy and hyperplasia. Adipose tissue is an endocrine organ producing many bioactive molecules, called adipokines. During obesity, dysfunctional adipocytes alter adipokine secretion, contributing to pathophysiology of obesity-associated diseases, including metabolic syndrome, type 2-diabetes, cardiovascular diseases and many types of malignancies. Circulating adiponectin levels are inversely correlated with BMI, thus adiponectin concentrations are lower in obese than normal-weight subjects. Many clinical investigations highlight that low adiponectin levels represent a serious risk factor in breast carcinogenesis, and are associated with the development of more aggressive phenotype. A large-scale meta-analysis suggests that BMI was positively associated with breast cancer mortality in women with ERα-positive disease, regardless menopausal status. This suggests the importance of estrogen signaling contribution in breast tumorigenesis of obese patients. It has been largely demonstrated that adiponectin exerts a protective role in ERα-negative cells, promoting anti-proliferative and pro-apoptotic effects, while controversial data have been reported in ERα-positive cells. Indeed, emerging data provide evidences that adiponectin in obese patients behave as growth factor in ERα-positive breast cancer cells. This addresses how ERα signaling interference may enhance the potential inhibitory threshold of adiponectin in ERα-positive cells. Thus, we may reasonably speculate that the relatively low adiponectin concentrations could be still not adequate to elicit, in ERα-positive breast cancer cells, the same inhibitory effects observed in ERα-negative cells. In the present review we will focus on the molecular mechanisms through which adiponectin affects breast cancer cell behavior in relationship to ERα expression.

Novel insights into adiponectin action in breast cancer: Evidence of its mechanistic effects mediated by ERα expression.

This review describes the multifaceted effects of adiponectin on breast cancer cell signalling, tumour metabolism, and microenvironment. It is largely documented that low adiponectin levels are associated with an increased risk of breast cancer. However, it needs to be still clarified what are the extents of the decrease of local/intra-tumoural adiponectin concentrations, which promote breast tumour malignancy. Most of the anti-proliferative and pro-apoptotic effects induced by adiponectin have been obtained in breast cancer cells not expressing estrogen receptor alpha (ERα). Here, we will highlight recent findings demonstrating the mechanistic effects through which adiponectin is able to fuel genomic and non-genomic estrogen signalling, inhibiting LKB1/AMPK/mTOR/S6K pathway and switching energy balance. Therefore, it emerges that the reduced adiponectin levels in patients with obesity work to sustain tumour growth and progression in ERα-positive breast cancer cells. All this may contribute to remove the misleading paradigm that adiponectin univocally inhibits breast cancer cell growth and progression independently on ERα status. The latter concept, here clearly provided by pre-clinical studies, may have translational relevance adopting adiponectin as a potential therapeutic tool. Indeed, the interfering role of ERα on adiponectin action addresses how a separate assessment of adiponectin treatment needs to be considered in novel therapeutic strategies for ERα-positive and ERα-negative breast cancer.

Study of Cord Blood Erythropoietin, Leptin and Adiponectin Levels in Neonates with Hypoxic Ischemic Encephalopathy.

Hypoxic ischemic encephalopathy (HIE) is a serious condition which results in neonatal morbidity and mortality. Early prediction of HIE especially in the first six hours of birth leads to early treatment with better prognosis. The aim of this study was to compare the concentrations of leptin, adiponectin, and erythropoietin between normal neonates and those with HIE for the possible use of these markers for assessment of the degree of HIE and as markers for early prediction of HIE. This study was carried out on 50 appropriate for gestational age (AGA) neonates with HIE born in Tanta University Hospital during the period from June 2016 to March 2018 (Group I). This study also included 50 appropriate for gestational age (AGA) normal neonates not suffering from any complications and matched with group I in age and sex as a control group (Group II). For all neonates in both groups, the following were done: Complete prenatal, natal, and postnatal history, assessment of APGAR score at 5 and 10 minutes, complete clinical examination with special account on clinical evidence of encephalopathy including hypotonia, abnormal oculomotor or pupillary movements, weak or absent suckling, apnea, hyperpnea, or seizures, measurement of cord blood gases and measurement of serum erythropoietin, leptin and adiponectin levels by ELISA immediately after birth. There were no significant differences between Group I and Group II regarding gestational age, male to female ratio, mode of delivery, and weight while there were significant differences regarding Apgar score at 1 and 5 minutes with significantly lower Apgar score at 1 and 5 minutes in group I compared with Group II. There were significantly lower cord blood PH and adiponectin level and significantly higher cord blood Leptin and erythropoietin in group I compared with group II. There were significant differences between cord blood adiponectin, leptin, erythropoietin, and PH in different degrees of HIE with significantly lower cord blood adiponectin and PH and significantly higher cord blood leptin and erythropoietin in severe degree of hypoxia compared with moderate degree and in moderate degree compared with mild degree of hypoxia. There was a significant positive correlation between cord blood erythropoietin and leptin and a significant negative correlation between cord blood erythropoietin and both adiponectin and PH in studied neonates with hypoxia. ROC curve showed that EPO had the best sensitivity and specificity followed by leptin then adiponectin while the PH had the least sensitivity and specificity as early predictors of hypoxic neonates. Neonates with HIE had lower cord blood PH and adiponectin levels and higher leptin and erythropoietin levels than normal healthy neonates at birth and during the early postnatal period. The significant differences between cord blood erythropoietin, leptin, and adiponectin between neonates with hypoxia compared with normal neonates may arouse our attention about the use of these markers in the cord blood as early predictors of neonatal HIE which can lead early treatment and subsequently better prognosis.

Lower Levels of Circulating Adiponectin in Elderly Patients with Metabolic Inflammatory Syndrome: A Cross-Sectional Study.

BackgroundMetabolic inflammation plays an important role in the pathogenesis of atherosclerosis, type 2 diabetes, non-alcoholic fatty liver disease, and obesity. The above metabolic disorders often coexist and are closely related with systemic low-grade inflammation. Metabolic inflammatory syndrome (MIS), a cluster of these four metabolic disorders, is a novel concept that is thought to be a better predictor of coronary heart disease than metabolic syndrome. Adiponectin is an adipokine that increases insulin sensitivity and antioxidation as well as has an anti-atherosclerosis effect. It is unclear whether adiponectin is associated with MIS. The objective of this study was to assess whether circulating adiponectin can be used as an indicator for MIS in elderly adults.MethodsA total of 136 elderly inpatients were divided into two groups: the MIS group and the non-MIS group. Characteristics, inflammatory markers, blood lipid metabolism, insulin resistance, and circulating adiponectin levels were assessed and compared between the two groups. Logistic regression analysis was used to explore the association between the associated factors and MIS.ResultsMIS patients were more likely to have a higher body mass index, have a higher fasting blood glucose level, be smokers, have fundus arteriosclerosis, have lower levels of adiponectin (4044.90 ± 3906.82 ng/mL vs 8503.89 ± 3523.89 ng/mL, p < 0.001), and have higher levels of inflammation (white blood cell and C-reactive protein) than non-MIS patients. Multiple factor analysis showed that lower adiponectin levels (OR = 22.937, p < 0.001) were independently associated with MIS. Adiponectin levels were lower in the vascular disease (2673.29 ± 1930.05 ng/mL vs 7194.38 ± 4615.83 ng/mL, p = 0.001), atherosclerosis (2374.14 [1496.41–4263.90] ng/mL vs 6037.48 [3865.61–10,373.60] ng/mL, p < 0.001), and type 2 diabetes (2391.73 [1386.41–4069.68] ng/mL vs 8916.03 [5801.14–12,724.45] ng/mL, p < 0.001) subgroups than in the non-MIS group.ConclusionLower adiponectin levels in serum are associated with MIS. Low adiponectin may be used as a biomarker for atherosclerosis in patients with MIS.

Metabolic Syndrome, and Particularly the Hypertriglyceridemic-Waist Phenotype, Increases Breast Cancer Risk, and Adiponectin Is a Potential Mechanism: A Case-Control Study in Chinese Women.

Objective: To investigate the association between metabolic syndrome and breast cancer and to elucidate the potential mechanism underlying this association.Patients and Methods: Based on baseline data drawn from 21 hospitals in 11 provinces of China, we performed a case–control study among 1,127 women (595 cases and 532 controls), divided into premenopausal, and postmenopausal subgroups. Student's t test, Pearson's χ2 test, and logistic regression analyses were performed to ascertain the association between breast cancer and metabolic syndrome, including all of its components. In addition, we attempted to clarify the potential role of adiponectin in this association.Results: Among the components of metabolic syndrome, abnormal waist circumference was the component that markedly increased breast cancer risk in premenopausal women (OR 1.447, 95% CI 1.043–2.006). Metabolic syndrome with clusters of special risk factors showed an association with breast cancer risk. Among all these components of metabolic syndrome, the hypertriglyceridemic-waist (HW) phenotype significantly increased breast cancer risk (OR 1.56, 95% CI 1.02–2.39), regardless of menopausal status, rendering it a strong predictor of breast cancer. Total adiponectin levels and high-molecular-weight adiponectin were reversely associated with metabolic syndrome. In addition, total adiponectin levels among breast cancer patients were much lower than among controls (p = 0.005) only in the HW phenotype subgroup. Furthermore, the HW phenotype was associated with increased risk of estrogen receptor/progesterone receptor-positive (ER+/PR+) breast cancer, with a 95% (OR = 1.95, 95% CI:1.21–3.13) increase. However, there was no significant association between the HW phenotype and both ER+/PR– and ER–/PR– subtypes. These results suggested that low adiponectin levels may be a mechanism that explains the association between the HW phenotype and breast cancer risk.Conclusion: Metabolic syndrome with special cluster factors is related to breast cancer risk; in particular, the HW phenotype can be regarded as a strong predictor of breast cancer. As an important factor involved in fat metabolism, adiponectin may strongly predict metabolic syndrome, especially the HW phenotype and breast cancer. Further research into this mechanism and epidemiological studies are needed. This study provides new evidence for the role of a healthy lifestyle in preventing breast cancer.

Biochemical Implications of Biotransformation of Some Toxic Floras Using Natural Local Enzyme Sources.

Recently, it has been established that simultaneous saccharification and fermentation is a potent technique for the detoxification of harmful plant materials. Following encouraging simultaneous medicinal applications of snail slime and yeast, we exploited their hydrolytic and fermentation potentials to prevent toxicities of the selected floras; Erythrodontium barteri (EB), bracken fern (BF), and crustose lichens (CL). The applicability of the saccharification process has been described in a patent (WO2005010193A2). The plants were bioprocessed using snail digestive juice and yeast slurry and their health effects were evaluated. Seventy rats were divided equally into groups, treated with single doses of aqueous extracts of the plants and their bioprocessed forms, and compared with control rats. The plants showed very high antinutrients levels, which significantly reduced after SSF with enhanced flavonoids, alkaloids and phenols. Potential alterations of WBC differentials, RBC, liver and renal function markers indices were mitigated by bioprocessed extracts. MDA, SOD, GRase, XO and XDH levels in rats administered the bEB and CL were equivalent to the levels found for the control rats. Some bioprocessed plants produced unaltered insulin, ghrelin, and leptin levels. The bioprocessed extracts, when compared to the effects of unprocessed extracts, produced lower TNF-α, Caspase-3, and adiponectin levels and mitigated the potential suppression of Na+/K+-ATPase levels. Potential depletion of inhibin-B, testosterone, estrogen, and prolactin was mitigated after bioprocessing. This study, thus, validates the application of bioprocessing using snail digestive juice and yeast as an effective approach to reduce the potential toxicities of harmful plants.

Seasonal affective disorder and seasonal changes in weight and sleep duration are inversely associated with plasma adiponectin levels

Overlapping pathways between mood and metabolic regulation have increasingly been reported. Although impaired regulation of adiponectin, a major metabolism-regulating hormone, has been implicated in major depressive disorder, its role in seasonal changes in mood and seasonal affective disorder-winter type (SAD), a disorder characterized by onset of mood impairment and metabolic dysregulation (e.g., carbohydrate craving and weight gain) in fall/winter and spontaneous alleviation in spring/summer, has not been previously studied. We studied a convenience sample of 636 Old Order Amish (mean (± SD), 53.6 (±14.8) years; 50.1% males), a population with self-imposed restriction on network electric light at home, and low prevalence of total SAD (t-SAD = syndromal + subsyndromal). We calculated the global seasonality score (GSS), estimated SAD and subsyndromal-SAD after obtaining Seasonal Pattern Assessment Questionnaires (SPAQs), and measured overnight fasting plasma adiponectin levels. We then tested associations between plasma adiponectin levels and GSS, t-SAD, winter-summer difference in self-reported sleep duration, and self-reported seasonal weight change, by using analysis of co-variance (ANCOVA) and linear regression analysis after adjusting for age, gender, and BMI. Participants with t-SAD (N = 14; 2.2%) had significantly lower plasma adiponectin levels (mean ± SEM, 8.76 ± 1.56 μg/mL) than those without t-SAD (mean ± SEM, 11.93 ± 0.22 μg/mL) (p = 0.035). In addition, there was significant negative association between adiponectin levels and winter-summer difference in self-reported sleep duration (p = 0.025) and between adiponectin levels and self-reported seasonal change in weight (p = 0.006). There was no significant association between GSS and adiponectin levels (p = 0.88). To our knowledge, this is the first study testing the association of SAD with adiponectin levels. Replication and extension of our findings longitudinally and, then, interventionally, may implicate low adiponectin as a novel target for therapeutic intervention in SAD.

A Metabolically Unhealthy Phenotype Is Associated with ADIPOQ Genetic Variants and Lower Serum Adiponectin Levels

Background: Even though excessive adipose tissue is related to chronic metabolic disturbances, not all subjects with excess weight (EW) display metabolic alterations, and not all normal-weight (NW) subjects have a metabolically healthy (MH) phenotype, probably due to gene-environment interactions. The aim of this study was to investigate the interaction effects of ADIPOQ and PPARG genetic variants in NW and EW individuals with different metabolic phenotypes. Methods: Data on 345 adults from western Mexico were analyzed. The individuals were classified into NW and EW groups according to body mass index, and were categorized as MH or metabolically unhealthy (MUH), considering homeostatic model assessment insulin resistance (HOMA-IR) and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) cut-off points for glucose, triglycerides, high-density lipoprotein cholesterol, and blood pressure. Subjects with ≤1 altered parameter were classified as MH. The single nucleotide polymorphisms (SNPs) –11377C>G, –11391G>A, +45T>G, and +276G>T for ADIPOQ and Pro12Ala for PPARG were analyzed by allelic discrimination. High-molecular-weight adiponectin isoform levels were measured by ELISA. Results: Lower serum adiponectin levels were associated with the MUH phenotype in EW subjects. NW subjects with the GG or TG genotype for the +45T>G SNP had reduced odds of the MUH phenotype. Individuals who carried two copies of the GG haplotype at the –11391G>A and –11377C>G SNPs for ADIPOQ had lower serum adiponectin levels than those with zero copies. Conclusion: In this population, lower serum adiponectin levels were found in the EW-MUH phenotype, and no differences were observed between the NW-MH and the EW-MH phenotype. In addition, the +45T>G SNP was associated with reduced odds of the MUH phenotype.

Expression of AdipoR1 and AdipoR2 and Serum Level of Adiponectin in Gastric Cancer

Background: Cancer is one of the major causes of death worldwide and the third leading cause of death in Iran. One of the proteins that are considered having anticancer effects is the adiponectin hormone. Adiponectin leads to programmed cell death, prevents cell growth and proliferation, and increases the expression levels of BCL2. Aim: The aim of this study was to assay the expression of adiponectin receptors (AdipoR1 and AdipoR2) genes in gastric cancer patients. Materials and Methods: In this case-control study, 42 gastric cancer patients and 52 volunteers as healthy controls were enrolled. Total RNA was extracted. cDNA was synthesized by the reverse transcription method, and expression analysis was performed by real-time PCR. The serum level of adiponectin was also measured by ELISA. Results: The expression of both AdipoR1 and AdipoR2 was significantly higher than the control group (p = 0.02). Serum adiponectin was significantly lower in gastric cancer cases when compared with normal controls (p = 0.03). Conclusion: We found that expression level of AdipoR1 and AdipoR2 is strongly higher; however, the level of circulating adiponectin is lower in gastric cancer. Our study suggests that the expression of AdipoR1 and AdipoR2, besides the low level of adiponectin, may play an important role in the development and/or progression of gastric cancer.

Association between adiponectin and insulin resistance in Egyptian patients with end-stage renal disease before and after kidney transplantation

Background Up to 50% of renal transplant recipients can experience diabetes mellitus (DM) and insulin resistance (IR). Both metabolic complications significantly increase the risk of progressive loss of renal function, cardiovascular morbidity, and death. On the contrary, the current body of evidence shows that changes in adiponectin, a cytokine of adipose tissue, is significantly associated with the development of DM and other components of metabolic syndrome. In the present study, the authors aimed to characterize the association between post-transplantation changes in adiponectin level and both IR and new-onset diabetes mellitus (NODM). Patients and methods The authors recruited 30 patients who received a living-donor kidney at least 6 months before study’s enrollment. Most patients were males (70%), with age ranged from 25 to 55 years. The following data were collected before the transplantation and at the end of follow-up: blood glucose profile, glycated hemoglobin, serum insulin, homeostasis model assessment-insulin resistance (HOMA-IR), lipid profile, and serum adiponectin. Results Six months after the transplantation, seven (23.3%) patients developed NODM. There was a negative correlation between serum adiponectin and HOMA-IR before and after kidney transplantation. Low adiponectin levels before and after transplantation was associated with a greater incidence of new onset diabetes after transplantation (NODAT). Patients who developed NODAT had lower levels of adiponectin compared with patients who did not develop NODAT before and after transplantation. Conclusion Low adiponectin level is associated with increased risk of NODM in renal transplant recipients. In addition, there is a negative correlation between serum adiponectin and IR before and after kidney transplantation.

Potential involvement of adiponectin in obesity-associated erosive esophagitis.

A strong causal relationship between obesity and erosive esophagitis has been proposed. Obesity may affect the pathogenesis of erosive esophagitis through adipokines as well as acid reflux. We evaluated the involvement of adiponectin in obesity-associated erosive esophagitis. In total, 1,902 patients who underwent endoscopy during medical check-ups were selected for study. Variables including the body mass index (BMI) and adiponectin level were compared between subjects with erosive esophagitis and normal controls. The subjects were classified by quartiles (Qs) of adiponectin level. Q4 was the reference group. The median adiponectin level differed by gender (men, 5.3 µg/ml vs women, 9.3 µg/ml; p<0.001). As the severity of erosive esophagitis increased in men, the BMI increased (p<0.001) while the adiponectin level decreased (p = 0.026). The multivariate odds ratio for erosive esophagitis was 1.79 for Q1, 1.73 for Q2, 2.34 for obesity, and 27.40 for hiatal hernia in men. When classified by obesity, the multivariate odds ratio for erosive esophagitis was 1.94 for Q1, 2.10 for Q2, and 18.47 for hiatal hernia only in obese men. In women, there were no trends in BMI, adiponectin levels, or severity of erosive esophagitis. We demonstrated that low adiponectin levels are involved in obesity-associated erosive esophagitis in men but not women.

The Role of Circulating Adiponectin and SNP276G>T at ADIPOQ Gene in BRCA-mutant Women.

Environmental factors may influence the lifetime risk of cancer (penetrance) in women with a BRCA mutation. In 89 BRCA-mutant women, affected or unaffected by breast/ovarian cancer, we explored serum levels of adipokines and their relation with the polymorphism SNP276G>T as modulators of BRCA penetrance. Affected women had significantly lower adiponectin than healthy women. Affected women with rs1501299 TT had significantly lower adiponectin and higher leptin than GT and GG genotypes. GT genotype was significantly associated with the disease status [odds ratio (OR)=3.24, 95% confidence interval (95% CI)=1.03-10.17]. Women in the lower tertile of serum adiponectin had a RR of BRCA-associated cancer of 2.80, 95% CI=1.1-7.1 (p for trend=0.03) compared with women in the higher tertile. In the SNP rs1501299 the T allele was significantly associated with lower serum levels of adiponectin in affected women, suggesting that the T allele might be related to cancer.

Impact of different exercise intensities on pregnant rats and on their offspring.

This study aimed at evaluating the levels of different maternal exercise intensities on maternal and fetal outcomes. Wistar rats were mated and the pregnant rats were distributed into four experimental groups (n = 13 animals/group): Control (Not exercise group - 0% of the anaerobic threshold- AT), mild (20%), moderate (80%), and heavy-exercise intensity (140% of AT). These AT were matched to the load of 0, 1, 4 and 7% of the body weight of the animal related to swimming-induced physical intensity. In pregnancy, biomarkers related to maternal blood gases, oxidative stress, metabolism, and reproductive performance, and outcomes of their offspring were analyzed. The mild and moderate-swimming caused no change on implantation, live fetus numbers and oxidative stress status. However, the rats submitted to mild-exercise presented respiratory alkalosis and the heavy-exercise group showed respiratory acidosis. In addition, fetuses of the heavy-exercise dams were smaller for gestational age and lower serum adiponectin levels compared to those of other groups. In conclusion, the moderate-exercise intensity caused beneficial effects for maternal environment and the mild and moderate-exercise presented similar fetal repercussions. Nevertheless, the heavy-exercise intensity caused maternal metabolic alterations that damaged the fetal growth. Therefore, these findings confirm that physical intensity should be carefully conducted to avoid maternal complications and, consequently, compromised fetal repercussions.

Mechanism of SEMA3G knockdown-mediated attenuation of high-fat diet-induced obesity.

Obesity is a worldwide health problem. Semaphorins are involved in axonal guidance; however, the role of secretory semaphorin 3G (SEMA3G) in regulating adipocyte differentiation remains unclear. Microarray analysis showed that the SEMA3G gene was upregulated in an in vitro model of adipogenesis. In this study, SEMA3G was highly expressed in the white adipose tissue and liver. Analysis of 3T3-L1 cell and primary mouse preadipocyte differentiation showed that SEMA3G mRNA and protein levels were increased during the middle stage of cell development. In vitro experiments also showed that adipocyte differentiation was promoted by SEMA3G; however, SEMA3G inhibition using a recombinant lentiviral vector expressing a specific shRNA showed the opposite results. Mice were fed a chow or high-fat diet (HFD); knockdown of SEMA3G was found to inhibit weight gain, reduce fat mass in the tissues, prevent lipogenesis in the liver tissue, reduce insulin resistance and ameliorate glucose tolerance in HFD mice. Additionally, the effect of SEMA3G on HFD-induced obesity was activated through PI3K/Akt/GSK3β signaling in the adipose tissue and the AMPK/SREBP-1c pathway in the liver. Moreover, the plasma concentrations of SEMA3G and leptin were measured in 20 obese and 20 non-obese human subjects. Both proteins were increased in obese subjects, who also exhibited a lower level of adiponectin and presented with insulin resistance. In summary, we demonstrated that SEMA3G is an adipokine essential for adipogenesis, lipogenesis, and insulin resistance and is associated with obesity. SEMA3G inhibition may, therefore, be useful for treating diet-induced obesity and its complications.