Adiponectin Protein Research Articles

Periodontal Treatment Improves Serum Levels of Leptin, Adiponectin, and C-Reactive Protein in Thai Patients with Overweight or Obesity.

Periodontitis and overweight or obesity independently change serum levels of leptin, adiponectin, and C-reactive protein (CRP). The aim of this study is to investigate the alterations of serum levels of leptin, adiponectin, and CRP after nonsurgical periodontal treatment (NSPT) in Thai patients with overweight or obesity (Owt/Ob) who did or did not exhibit severe periodontitis (SP) and normal weight (Nwt) patients with or without SP. Two hundred sixty patients were screened; 29 patients were included in this study. The study participants comprised 6 patients with Owt/Ob who exhibited SP, 11 patients with Owt/Ob who did not exhibit SP, 5 Nwt patients with SP, and 7 Nwt patients without SP. Periodontal disease status was evaluated; serum levels of leptin, adiponectin, and CRP were determined by enzyme-linked immunosorbent assay at baseline, as well as at 3 and 6 months after NSPT. At 3 months after NSPT, periodontal status was improved in all groups (p < 0.05), except Nwt patients without SP. Serum levels of leptin and CRP were significantly reduced, while serum levels of adiponectin were elevated after NSPT, regardless of bodyweight or waist circumference (p < 0.05). Improvement in serum levels of leptin after NSPT was also observed in the Nwt with SP group (p = 0.015); these levels did not significantly differ in Nwt patients without SP. NSPT reduces serum levels of leptin and CRP and enhances serum levels of adiponectin in Thai patients with Owt/Ob, irrespective of periodontitis severity. These results suggest a role for periodontal treatment in the systemic inflammatory response of Thai people with Owt/Ob.

Insulin resistance and the adiponectin/leptin ratio as a surrogate measure of insulin resistance in Japanese collegiate baseball players.

No study has previously investigated insulin resistance in collegiate baseball players. The purposes of this study were to examine: 1) the insulin resistance; and 2) the usefulness of the adiponectin/leptin (A/L) ratio compared with the homeostasis model assessment of insulin resistance (HOMA-IR) for assessing insulin resistance in collegiate baseball players. Twenty collegiate baseball players with abdominal obesity (AO group) defined by a waist circumference (WC) ≥85 cm, 65 lean baseball players with a WC<85 cm (L group), and 20 controls who were sedentary for at least 1 year (C group) were compared. The Body Mass Index, WC, systolic and diastolic blood pressures, fasting plasma glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, apolipoprotein B, insulin, leptin, adiponectin, and high-sensitivity C-reactive protein (hs-CRP) were measured. The AO group had a significantly higher insulin level, HOMA-IR, and leptin level, and lower A/L ratio than the L and C groups. The AO group had a significantly higher prevalence of insulin resistance (50%) than the L (14%) group. The A/L ratio was significantly negatively correlated with body weight, Body Mass Index, WC, triglycerides, triglycerides/HDL-C ratio, apolipoprotein B, hs-CRP, insulin, HOMA-IR, and leptin, and positively correlated with HDL-C, whereas HOMA-IR was significantly positively correlated with body weight, Body Mass Index, WC, systolic and diastolic blood pressures, fasting plasma glucose, and insulin, and negatively correlated with adiponectin and the A/L ratio. In the forward stepwise multiple regression analysis, WC, triglycerides, and hs-CRP were the significant determinants for the A/L ratio, whereas diastolic blood pressure and WC were the significant determinants for HOMA-IR. This model explained 53.7% of the variance in the A/L ratio and 13.6% of the variance in HOMA-IR. The present study suggested that the baseball players with abdominal obesity had a significantly higher prevalence of insulin resistance than the lean baseball group. The A/L ratio may be more useful than HOMA-IR to accurately assess insulin resistance in male collegiate baseball players.

Incidence of Atrial Fibrillation in Postmenopausal Women with Endometrial Cancer.

Endometrial cancer (EC) has been associated with an increased risk of cardiovascular disease, including atrial fibrillation (AF). We performed a prospective, case-controlled analysis among 310 Bulgarian women with new-onset, histologically confirmed EC, free of AF at the baseline survey, and women with normal (senile) endometrium/endometrial hyperplasia as a control group (n = 205). The risk of AF as well as relationship of adiponectin (APN) and high sensitivity C-reactive protein (hs-CRP) levels with AF in women with EC were calculated by Cox proportional hazards models. During the mean follow-up of 2.5 ± 0.5 years, new-onset AF had occurred in 11.7% of women with EC vs. 5.8% in the control group (p < 0.01). The risk of AF was highest in the first 6 months after new-onset EC, with an incidence rate ratio (IRR) of 1.19 (95% CI 1.10–1.29; p = 0.01). Women with EC, who were obese (body mass index (BMI) > 30 kg/m2) and younger (age < 60) were found to be more likely to develop AF (HR 1.95; 95% CI 1.18–3.32; p = 0.05). APN levels were not significantly associated with new-onset AF (95% CI 0.87–1.21; p = 0.063). However, the secondary analysis showed evidence of APN–AF association when adjusted for BMI (2.05; 95% CI 1.04–4.04; p = 0.037). We conclude that EC was significantly associated with the incidence of AF.

Adipokines and C-reactive protein as indicators of MetS presence in obese Greek children: The Healthy Growth Study

Metabolic syndrome (MetS) occurs in a proportion of overweight and obese children and increases their future risk of serious health complications, even in adolescence and young adulthood. We aimed to explore the role of certain adipokines and inflammatory markers in identifying children with MetS. This study is a secondary analysis of data coming from the Healthy Growth Study, a cross-sectional study conducted with schoolchildren in Greece. The present study included data from a representative sample of 1376 schoolchildren (mean age: 11.19 ± 0.66 years), recruited from 77 primary schools in four large regions in Greece. Anthropometric, clinical and biochemical data were recorded. Children's body weight status and the presence of MetS were determined and their correlation with the serum levels of leptin, adiponectin and C-reactive protein (CRP) was explored. The prevalence of the MetS was 21.7 % and 3.7 % in obese and overweight children, respectively. The balance of adipokines was disturbed in obesity, as the serum level of adiponectin decreased as body weight increased, while the serum level of leptin increased. The serum level of the inflammatory marker CRP increased significantly as body weight increased. Discriminant analysis showed that these factors could distinguish the children with MetS as compared to children with no MetS. In the under study Mediterranean childhood population, monitoring of the levels of adipokines and CRP could identify the overweight and obese children with MetS. Appropriate individualized dietary and lifestyle interventions can be applied in these children to prevent health complications associated with MetS.

Early Predictors of Gestational Diabetes Mellitus in IVF-Conceived Pregnancies

ObjectiveGestational diabetes mellitus (GDM) is associated with adverse maternal and fetal outcomes. This study aimed to identify early and reliable GDM predictors that would enable implementation of preventive and management measures. MethodsThe participants were a 28-week prospective cohort of in vitro fertilization (IVF)-conceived pregnant women (≤39 years, body mass index [BMI] 18.5-38 kg/m2) without a known history of diabetes mellitus. Fasting blood samples were analyzed at baseline (pre-IVF) and 12 weeks’ gestation for reproductive hormones, glucose, serum insulin, lipids, thyroid function, adiponectin, and lipopolysaccharide-binding protein. At 28 weeks, a 75-g oral glucose tolerance test was used to screen for GDM. ResultsFor the overall group at baseline, 22% had BMI ≥30 kg/m2, 45% had polycystic ovary syndrome, 16% had hemoglobin A1C of 5.7% to 6.1%, and 14% had a past history of GDM. At 28 weeks of gestation (n = 158), 34 women had developed GDM and 124 had not. Significant baseline predictors of GDM onset included greater BMI (29.0 vs 25.8 kg/m2), older age (34 vs 32 years), higher levels of follicle-stimulating hormone/luteinizing hormone ratio (1.2 vs 1.0), hemoglobin A1C (5.5 vs 5.2%), insulin (10.6 vs 7.1 μIU/mL), homeostatic model assessment of insulin resistance (2.2 vs 1.7), total cholesterol (199 vs 171 mg/dL), and low-density lipoprotein cholesterol (123 vs 105 mg/dL), and lower triglyceride levels (74 vs 76 mg/dL). Significant 12-week GDM predictors included greater maternal weight gain (delta: 3.4 vs 1.5 kg) and higher levels of insulin (11.3 vs 7.6 μIU/mL), triglycerides (178 vs 120 mg/dL), and homeostatic model assessment of insulin resistance (2.3 vs 1.5). Twelve-week BMI is a predictor of GDM following adjustment for polycystic ovary syndrome status and maternal age. ConclusionWhile preconception maternal BMI, age, and follicle-stimulating hormone/luteinizing hormone ratio are predictors of subsequent development of GDM, early IVF-conceived gestational weight gain is the best predictor of GDM onset.

Plasma adipokines and glycaemic progression among African Americans: Findings from the Jackson Heart Study.

To evaluate the association between plasma biomarkers including leptin, adiponectin, adiponectin-to-leptin ratio and high-sensitivity C-reactive protein (hsCRP) with risk of glycaemic progression and incident dysglycaemia (pre-diabetes or diabetes) in a community-based sample of African American (AAs). We analysed data from 3223 participants without type 2 diabetes at baseline (2000-2004) who attended ≥1 follow-up visit. Poisson regression was used to generate risk ratios (RRs) for glycaemic progression and incident dysglycaemia. Over a median of 7 years, 46.4% developed glycaemic progression (n=1495). After adjusting for demographic and lifestyle variables, the RRs (95% CI) for glycaemic progression comparing highest (Q4) to lowest (Q1) quartiles were 1.30 (1.10-1.54), 0.74 (0.65-0.84), 0.70 (0.62-0.80) and 1.22 (1.07-1.38) for leptin, adiponectin, adiponectin-leptin ratio and hsCRP, respectively. Upon additional adjustment for BMI, the corresponding RRs (95% CIs) were 1.15 (0.94-1.42), 0.76 (0.67-0.86), 0.72 (0.62-0.84) and 1.14 (0.99-1.31) respectively. Among participants with normal glycaemia, the RRs (95% CIs) for incident pre-diabetes in Q4 vs Q1 were 1.37 (1.13-1.67), 0.73 (0.63-0.85), 0.70 (0.59-0.82) and 1.28 (1.10-1.48) for leptin, adiponectin, adiponectin-leptin ratio and hsCRP, respectively; equivalent RRs for incident diabetes were 5.15 (2.63-10.10), 0.36 (0.20-0.68), 0.21 (0.12-0.38) and 3.04 (1.70-5.44), respectively. In this large community-based cohort of AAs, our results suggest that high plasma leptin and hsCRP, as well as low adiponectin and adiponectin-to-leptin ratio, are associated with higher risks of glycaemic progression. The findings point to the potential utility of these biomarkers in predicting and preventing glycaemic progression in this high-risk population.

Perivascular adipose tissue from the internal mammary artery in patients with severe coronary artery atherosclerosis.

he internal mammary artery (IMA) is routinely used as an arterial graft for coronary artery bypass grafting with an excellent long‑term patency rate, but its protective mechanism is unclear. We evaluated the differences between the expression of several gene in perivascular adipose tissue from the IMA (PVAT‑IMA) as compared with other fat depots in patients with severe coronary artery disease. A total of 53 patients (13 women) with severe coronary artery disease and preserved left ventricular ejection fraction were scheduled for coronary artery bypass grafting. Clinical assessment, anthropometric parameters, and quantification of fat depots were performed in all patients. The relative expression of the following genes were obtained in PVAT‑IMA, as well as epicardial, pericardial, and subcutaneous (SF) fat samples: angiotensinogen (AGT), angiotensin I converting enzyme 1 and 2 (ACE1and ACE2), glucagon‑like peptide receptors type 1 and 2 (GLP1R and GLP2R), phospholipid transfer protein (PLTP), adiponectin (ADIPOQ), omentin‑1 (ITLN1), and uncoupling protein 1 (UCP1). The expression of UCP1 (median [interquartile range [IQR], 2.5 [0.91-16.6]; P <0.01) and AGT(2.22 [0.65-6.2]; P <0.01) was higher in PVAT‑IMA compared with the SF depot. ADIPOQ expression was lower in pericardial and epicardial fat depots (median [IQR], 0.44 [0.23-2.3]; P <0.01). The expression of ITLN1 was increased in PVAT‑IMA as compared with epicardial and pericardial fat (P <0.001). PVAT‑IMA revealed differences in the expression of selected genes in relation to SF. We found a higher expression of ITLN1 in PVAT‑IMA compared with other adipose tissue depots, which could be associated with protective mechanisms against atherosclerosis in IMA. However, this remains a subject for further studies.

Increased vascular permeability and severe renal tubular damage after ischemia-reperfusion injury in mice lacking adiponectin or T-cadherin.

Adiponectin (APN) is a circulating protein specifically produced by adipocytes. Native APN specifically binds to T-cadherin, a glycosylphosphatidylinositol-anchored protein, mediating the exosome-stimulating effects of APN in endothelial, muscle, and mesenchymal stem cells. It was previously reported that APN has beneficial effects on kidney diseases, but the role of T-cadherin has not been clarified yet. Here, our immunofluorescence study indicated the existence of both T-cadherin and APN protein in pericytes, subsets of tissue-resident mesenchymal stem/progenitor cells positive for platelet-derived growth factor receptor β (PDGFRβ), surrounding peritubular capillaries. In an acute renal ischemia-reperfusion (I/R) model, T-cadherin-knockout (Tcad-KO) mice, similar to APN-KO mice, exhibited the more progressive phenotype of renal tubular damage and increased vascular permeability than wild-type mice. In addition, in response to I/R-injury, the renal PDGFRβ-positive cell area increased in wild-type mice, but opposingly decreased in both Tcad-KO and APN-KO mice, suggesting severe pericyte loss. Mouse primary pericytes also expressed T-cadherin. APN promoted exosome secretion in a T-cadherin-dependent manner. Such exosome production from pericytes may play an important role in maintaining the capillary network and APN-mediated inhibition of renal tubular injury. In summary, our study suggested that APN protected the kidney in an acute renal injury model by binding to T-cadherin.NEW & NOTEWORTHY In the kidney, T-cadherin-associated adiponectin protein existed on peritubular capillary pericytes. In an acute renal ischemia-reperfusion model, deficiency of adiponectin or T-cadherin exhibited the more progressive phenotype of renal tubular damage and increased vascular permeability, accompanied by severe pericyte loss. In vitro, adiponectin promoted exosome secretion from mouse primary pericytes in a T-cadherin-dependent manner. Adiponectin plays an important role in maintaining the capillary network and amelioration of renal tubular injury by binding to T-cadherin.

Integrative metabolomics‐genomics approach reveals that pathways related to the metabolism of acylcarnitines and amines are new potential targets of Alzheimer’s disease

AbstractBackgroundThe metabolic basis of Alzheimer’s Disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis remain elusive. In this study, we systematically interrogated metabolomics, genetics, proteomics, and clinical data from the matched subjects in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to identify key drivers and metabolic pathways associated with changes in metabolites with disease severity.Method140 Metabolites in fasting serum samples from the ADNI (362 controls, 94 significant memory concerns, 764 mild cognitive impairment, and 298 AD) were analyzed using the AbsoluteIDQ‐p180 kit. Values adjusted for age, gender, body mass index (BMI), education, cohort, and medication. A metabolite co‐expression network was constructed using Multiscale Embedded Gene co‐Expression Network Analysis (MEGENA). Co‐expressed metabolite modules were then prioritized for the strength of association with clinical/cognitive and pathology biomarker variables. Correlation analysis of the co‐metabolite modules and the matched gene/protein expression data was performed. The ROS/MAP cohort was used as a replication study of the co‐expression network. Six brain transcriptomic datasets from the Mount Sinai Brain Bank, ROS/MAP, and MAYO clinic cohorts were utilized to build up gene‐centered correlation networks to elucidate functions of upstream regulators of candidate metabolites.ResultModules comprised of short‐chain acylcarnitines/amino acids (M8, M3), and medium/long‐chain acylcarnitines (M6) were most associated with worse AD clinical outcomes, including episodic memory scores and disease severity (CDR‐SB) (Figure 1A‐C). CPT1A gene expression was highly correlated with an increased level of the medium/long‐chain acylcarnitines (corrected p‐value = 1.87 × 10‐6). Increased ABCA1 gene expression and adiponectin protein (a regulator of ABCA1) levels corresponded to decreased short‐chain acylcarnitines and amines in AD (corrected p‐value &lt; 0.02) (Figure 2A‐C). In addition, CPT1A and ABCA1 were differently expressed in the brains of AD patients compared to controls (Table 1), and their subnetworks were enriched for AD, aging, and neuronal system‐related gene signatures/pathways (Figure 3A‐D). Eight out of eleven modules were highly preserved between the ADNI and ROS/MAP cohorts (Z summary preservation score &gt; 5; corrected p‐value &lt; 0.05).ConclusionIdentification of acylcarnitines enriched modules and their potential upstream genetic and transcriptional regulators paves the way for developing novel biomarkers and targets for AD.

Evaluation of the correlation between serum lipid characteristics of obese subjects and ADIPOQ gene rs266729 polymorphism in Chaharmahal and Bakhtiari Province of Iran

Obesity is a multifactorial disorder that is influenced by various factors such as behavior, diet, environment, metabolic and genetic. This disease is the result of an imbalance between energy absorption and expenditure. Mutations in genes that are responsible for appetite control and metabolism are considered as the genetic component of obesity. Adiponectin protein is one of the most effective adipokines in regulating the body's energy homeostasis and fat storage, which is expressed by the ADIPOQ gene and secreted from white adipose tissue. The concentration of this protein in the blood decreases in obesity. In this study, the relationship between rs266729 polymorphism in the ADIPOQ gene with the level of biochemical parameters such as total cholesterol and triglyceride and HDL and LDL in the blood of obese people in Borujen (a city in Iran) was investigated. This study was performed on 100 people who referred to the Tamin Ejtemaee clinic due to obesity problems in Borujen. In this study, the ARMS-PCR method was used to determine the genotype of individuals. Based on the results of this study, no significant relationship was found between biochemical parameters including total cholesterol, triglyceride, and LDL with rs266729 polymorphism genotypes in ADIPOQ gene in obese subjects. We concluded that rs266729 polymorphism cannot be useful as an index parameter for predispose genotype for imbalance in total cholesterol, triglyceride, and LDL levels in a person.

Causal association of adipokines with osteoarthritis: a Mendelian randomization study.

This two-sample Mendelian randomization study aimed to delve into the effects of genetically predicted adipokine levels on OA. Summary statistic data for OA originated from a meta-analysis of a genome-wide association study with an overall 50508 subjects of European ancestry. Publicly available summary data from four genome-wide association studies were exploited to respectively identify instrumental variables of adiponectin, leptin, resistin, chemerin and retinol-blinding protein 4. Subsequently, Mendelian randomization analyses were conducted with inverse variance weighted (IVW), weighted median and Mendelian randomization-Egger regression. Furthermore, sensitivity analyses were then conducted to assess the robustness of our results. The positive causality between genetically predicted leptin level and risk of total OA was indicated by IVW [odds ratio (OR): 2.40, 95% CI: 1.13-5.09] and weighted median (OR: 2.94, 95% CI: 1.23-6.99). In subgroup analyses, evidence of potential harmful effects of higher level of adiponectin (OR: 1.28, 95% CI: 1.01-1.61 using IVW), leptin (OR: 3.44, 95% CI: 1.18-10.03 using IVW) and resistin (OR: 1.18, 95% CI: 1.03-1.36 using IVW) on risk of knee OA were acquired. However, the mentioned effects on risk of hip OA were not statistically significant. Slight evidence was identified supporting causality of chemerin and retinol-blinding protein 4 for OA. The findings of this study were verified by the results from sensitivity analysis. An association between genetically predicted leptin level and risk of total OA was identified. Furthermore, association of genetically predicted levels of adiponectin, leptin and resistin with risk of knee OA were reported.

Sfrp5/Wnt5a and leptin/adiponectin levels in the serum and the periarterial adipose tissue of patients with peripheral arterial occlusive disease

BackgroundLeptin, adiponectin, secreted frizzled-related protein 5 (Sfrp5) and wingless-type family member 5a (Wnt5a) are novel adipokines that are involved in insulin sensitivity and atherosclerosis. The aim of the present study was to investigate the serum and periarterial adipose tissue leptin/adiponectin and Sfrp5/Wnt5a levels in patients with peripheral arterial occlusive disease (PAOD). MethodsA total of 75 patients with PAOD and 39 control subjects were recruited. The serum concentrations of leptin, adiponectin, Sfrp5 and Wnt5a were measured by ELISAs, and the leptin, adiponectin, Sfrp5 and Wnt5a levels in the periarterial adipose tissue were observed by western blotting. ResultsThe serum Sfrp5 levels were significantly lower in the patients with PAOD than in the control subjects (p < 0.001) and Wnt5a levels were higher in the patients with PAOD (p < 0.001). The serum leptin levels were significantly higher in the patients with PAOD than in the control subjects (p < 0.001), and adiponectin levels were significantly lower in the patients with PAOD (p < 0.001). The serum Sfrp5 levels were associated with ABI (rs = 0.274; p = 0.018), Wnt5a (rs = −0.409; p < 0.001), adiponectin (rs = 0.244; p = 0.035) and Leptin/Adiponetin ratio (rs = −0.244; p = 0.037). The adiponectin and Sfrp5 protein levels were decreased in the periarterial adipose tissue of patients with PAOD compared with control subjects. The leptin and Wnt5a protein levels were increased in the periarterial adipose tissue of patients with PAOD compared with control subjects. ConclusionWe demonstrated that the adiponectin and Sfrp5 levels in the serum and periarterial adipose tissue were significantly lower in the patients with PAOD than in the control subjects. The leptin and Wnt5a levels in the serum and periarterial adipose tissue were significantly higher in the patients with PAOD than in the control subjects.

The Endocrine Role of Adipose Tissue and Its Management of Obesity-Related Diseases.

Adipose tissue plays a central role in regulating whole-body energy. Moreover, adipose tissue acts as an endocrine organ and produces numerous bioactive factors called adipokines which communicate with other organs and modulate a range of metabolic pathways: proteins (adiponectin, angiopoietins, chemerin, etc.), lipids (fatty acid esters of hydroxyl fatty acids, lysophosphatidic acids and sphingolipids), metabolites (uric acid and uridine) and microRNAs. However, excessive adipose tissue is associated with a chronic state of low-grade inflammation, caused by unbalanced production or secretion of these adipokines and can contribute to the development of obesity [1].

The effects of testosterone replacement therapy in men with age-dependent hypogonadism on body composition, and serum levels of leptin, adiponectin, and C-reactive protein.

Age-related hypogonadism in men leads to abnormal body composition development and overproduction of inflammatory cytokines, and thus has atherogenic and potentially cancer promoting effects. The aim of the study was to assess the effect of agedependent testosterone deficiency replacement in men on body composition, serum leptin, adiponectin, and C-reactive protein levels. Men aged 50-65 years (56.0 ± 5.7, average ± SD), with total testosterone levels < 4 ng/mL, and clinical symptoms of hypogonadism were divided into two groups of 20 men and treated with testosterone (200 mg/two weeks intramuscularly) or placebo during 12 months. Twelve months of treatment with testosterone led to body mass index (BMI) and fat mass (FM) decrease from 26.6 ± 2.1 to 26.1 ± 1.8 kg/m², p < 0.05, and from 17.0 ± 4.4 to 15.6 ± 4.0 kg, p < 0.05, respectively. Body mass index and FM did not change in placebo-receiving subjects. Serum leptin and highly selective C-reactive protein (hsCRP) levels in testosterone group decreased from 6.2 ± 1.4 to 4.0 ± 1.2 μg/L, p < 0.05, and from 1.4 ± 1.2 to 1.0 ± 1.0 mg/L, p < 0.05 after 12 months, respectively. Adiponectin increased from 7.6 ± 2.5 μg/mL to 9.4 ± 2.8 μg/mL, p < 0.05 in the same time. In the placebo group serum leptin, adiponectin, and hsCRP levels did not change significantly. Testosterone replacement in men with age-related hypogonadism causes a decrease in body mass index, fat mass, serum leptin, and C-reactive protein levels and increases serum adiponectin levels.

Comparison of Visceral Fat Reduction by Ipragliflozin and Metformin in Elderly Type 2 Diabetes Patients: Sub-Analysis of a Randomized-Controlled Study.

IntroductionTo compare the effects of ipragliflozin, a sodium-glucose transporter 2 inhibitor, with those of metformin on visceral fat (as well as muscles and bones) in Japanese elderly patients with type 2 diabetes (T2D), we conducted a sub-analysis of a prospective, multicenter, blinded-endpoint randomized-controlled study.MethodsIn total, 103 patients with T2D (body mass index ≥ 22 kg/m2; glycated hemoglobin, 7–10%) and being treated with sitagliptin (a dipeptidyl peptidase-4 inhibitor) were included and randomized to receive ipragliflozin or metformin. The primary outcome was the change in visceral fat area measured using computed tomography 24 weeks following treatment. The secondary outcomes included changes in subcutaneous and total fat area, muscle volume, bone density measured using computed tomography, handgrip strength, bone markers, plasma glucose, insulin, homeostasis model assessment (HOMA)2-beta, HOMA2-R, glycated hemoglobin, lipid panel, uric acid, blood pressure, adiponectin, and high-sensitivity C-reactive protein. All patients aged 65–74 years were selected for sub-analysis.ResultsThe sub-analysis included 15 and 14 patients in the ipragliflozin and metformin groups, respectively. The patients’ backgrounds were well balanced. Visceral fat area reduction was greater in the ipragliflozin group than in the metformin group (− 10.58% vs. − 6.93%; P = 0.034). There were significant differences in the changes in bone absorption markers, uric acid, and total cholesterol levels between the groups.ConclusionIpragliflozin significantly reduced the visceral fat area compared with metformin when added to sitagliptin in elderly patients with T2D. Long-term and large-scale studies are required to elucidate whether ipragliflozin is suitable for elderly patients.Trial RegistrationThe study was registered at https://www.umin.ac.jp/ctr/ (UMIN-ID: UMIN 000015170).Electronic supplementary materialThe online version of this article (10.1007/s13300-020-00949-0) contains supplementary material, which is available to authorized users.

Expression and localization of adiponectin and its receptors (AdipoR1 and AdipoR2) in the hypothalamic-pituitary-ovarian axis of laying hens

Adiponectin is a hormone secreted by adipose tissue that is involved in the regulation of energy homeostasis and reproduction. In this study, the expression levels of adiponectin and its receptors in the hypothalamic-pituitary-ovarian (HPO) axis of laying hens were investigated using quantitative real-time PCR (qRT-PCR) and Western blotting, and the localization of these proteins was explored using immunohistochemistry. The morphological relationships between adiponectin receptors and gonadotropin-releasing hormone (GnRH) neurons were analyzed using double immunofluorescence labeling. The results showed that adiponectin mRNA and protein were widely expressed in all tissues involved in the HPO axis in laying hens, with especially high expression in the hypothalamus. Both AdipoR1 and AdipoR2 were more highly expressed in the pituitary than in other tissues and exhibited similar mRNA and protein expression patterns. The immunohistochemistry results showed that adiponectin and AdipoR2 were localized in the major hypothalamic nuclei that regulate food intake and energy balance (i.e., the lateral hypothalamic area (LHA), infundibular nucleus (IN), dorsomedial nucleus (DMN), and paraventricular nucleus (PVN)). Immunostaining revealed that adiponectin and its receptors were also localized in the cytoplasm of cells in the adenohypophysis. In the ovaries, adiponectin was localized in the granulosa layer, in the theca externa of follicles and in basal cells, while AdipoR1 and AdipoR2 were localized in basal cells. In the double immunofluorescence labeling experiment, AdipoR1 and AdipoR2 were localized in GnRH neurons in the IN and DMN. These results suggest that adiponectin and its receptors may play major roles in the endocrine network, which integrates energy balance and reproduction.

Evaluation of Changes in the Expression Profile of mRNA and Proteinencoding Adiponectin in Ishikawa Cell Line under the Influence of Cisplatin - Preliminary Report.

Background A reduced concentration of adiponectin is considered as an independent factor of the risk of inducing endometrial cancer. Cisplatin is a drug used in the therapy of this type of neoplasm. However, knowledge of the effects of cisplatin on the adiponectin level is still limited.Objective The purpose of this study was to assess the impact of cisplatin depending on the concentration and time of exposition of the cells to the drug on the adiponectin level in the endometrial cancer cell line.Methods Cells of endometrial cancer cell line Ishikawa were exposed for 12,24 and 48 hour periods to cisplatin with the following concentrations: 2.5µM, 5µM, 10µM. The changes in the expression profile of adiponectin were compared to the RtqPCR reaction and ELISA test. The STATISTICA 13.0 PL program was used for statistical analysis (p<0.05).Results In the culture without the drug, the concentration of adiponectin was statistically lower than in the cell culture incubated with the drug. Changes on the mRNA level seem to be more specific than on the protein level, although in both cases, the same trend in the expression changes was noted.DiscussionThe longer the time of exposition of the cells to the drug, the expression of mRNA, and the adiponectin protein increased. Changes in the expression profile were characterized statistically (p<0.05).Conclusion Cisplatin, in a noticeable way, changes the expression profile of adiponectin. Molecular analysis indicated that in the case of endometrial cancer therapy should be implemented with a concentration of no less than 5 µM.

Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1-SIRT1-PGC-1α.

Adiponectin stimulates mitochondrial biogenesis through peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), a major regulator of mitochondrial biogenesis. MOTS-c (mitochondrial open reading frame of the 12S rRNA) is a biologically active mitochondrial-derived peptide encoded by mitochondrial DNA. It influences the mechanisms of obesity and diabetes. We hypothesised that the adiponectin pathway may regulate the production and/or secretion of MOTS-c in skeletal muscle. We aimed to determine whether exercise and adiponectin affect MOTS-c to improve insulin resistance in mice. To investigate this hypothesis, we used wild-type C57BL/6 mice subjected to high-fat diet, an exercise regimen, and i.p. injection of recombinant mouse adiponectin (Acrp30) or MOTS-c, and adiponectin knockout (Adipoq-/-) mice (C57BL/6 background) subjected to i.p. injection of Acrp30. C2C12 myotubes were also treated with sirtuin 1 (SIRT1) inhibitor, PGC-1α inhibitor, SIRT1 activator, plasmid-expressed active APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper), pcDNA-SIRT1, or siRNA against APPL1, SIRT1 or PGC-1α. In Adipoq-/- mice, MOTS-c levels in the plasma and skeletal muscle were downregulated. In C2C12 myotubes, adiponectin increased the mRNA expression of MOTS-c. APPL1 protein level following adiponectin treatment positively correlated with MOTS-c protein and mRNA levels in C2C12 myotubes. SIRT1 overexpression increased the adiponectin-induced mRNA and protein expression of MOTS-c, SIRT1 and PGC-1α. Pharmacologic and genetic inhibition of PGC-1α suppressed the increases in MOTS-c mRNA and protein levels induced by SIRT1 overexpression. In mice, plasma and skeletal muscle MOTS-c levels were significantly downregulated following high-fat-diet. Exercise and i.p. Acrp30 or MOTS-c increased MOTS-c levels and adiponectin mRNA and protein expression in the plasma and skeletal muscle. Our findings showed that the APPL1-SIRT1-PGC-1α pathway regulates the production and/or secretion of skeletal muscle MOTS-c by mediating adiponectin signalling. Our study provides an insight into the cellular and molecular pathways underlying the pathogenesis of diabetes and shows that MOTS-c is a potential novel therapeutic target in the treatment of diabetes. Graphical abstract.

Sex dimorphism in the associations of gestational diabetes with cord blood adiponectin and retinol-binding protein 4

IntroductionGestational diabetes (GD) is associated with impaired insulin sensitivity in newborns. Adiponectin and retinol-binding protein 4 (RBP-4) are involved in regulating insulin sensitivity. Females are more likely to develop diabetes...

Effects of Viburnum opulus fruit extracts on adipogenesis of 3T3-L1 cells and lipase activity

In this study, the anti-obesity effect and mechanism of action of Viburnim opulus fruit crude extract (CE) and semi-purified phenolic extract (SPPE) in 3T3-L1 cells were studied. In addition, inhibitory activity of extracts against pancreatic lipase in triolein emulsion was estimated, as well as their phenolic profiles by UPLC/Q-TOF-MS. Twenty four phenolic compounds were identified in both extracts with chlorogenic acid as the dominant compound. The inhibition mode of extracts against lipase was competitive and SPPE demonstrated synergistic action with orlistat. Both extracts had the ability to inhibit adipogenesis process in a dose-dependent manner. Cells treatment with extracts at 75 µg/mL concentration was not only sufficient to inhibit lipids accumulation at almost 20%, but also influenced the size of lipid droplets. CE and SPPE reduced intracellular reactive oxygen species production by 20% and leptin level by 21–30%. They did not affect the peroxisome proliferator-activated receptor-gamma and adiponectin protein expression levels.