Protective Role Of Adiponectin Research Articles

Abstract 181: Adiponectin Alleviates Acute Murine Pulmonary Injury Post Cardiopulmonary Resuscitation

Objective: Patients with cardiac arrest (CA) are often suffering from pulmonary ischemia-reperfusion injury after active cardiopulmonary resuscitation (CPR) and return of spontaneous circulation (ROSC). In recent years, previous studies have found that acute lung injury (ALI) after ROSC could be an independent risk factor for the prognosis of out of hospital cardiac arrest (OHCA). However, there is still a lack of effective therapy for pulmonary injury caused by CA-CPR-ROSC with no side effects. Methods: C57BL/6 male mice, aged from 8 to 10 weeks were purchased from Dossy Experimental Animals Co. Ltd (Chengdu, China). All the mice were feeding and drinking freely in the animal room of Sichuan University West China Science and Technology Park for one week. The experiments involving mice were approved by the Ethics Committee from West China Hospital of Sichuan University (approval No.2017071A). At the day before experiment, mice were given fasting treatment but allowed to drink water freely. CA-CPR-ROSC could cause global cerebral ischemia injury in vivo. APN (10μg/0.05ml per mice) was intravenously injected to mice at 10 min after restoration of spontaneous circulation (ROSC). Computed tomography (CT) scan of the lungs was performed before executing the animals. We used the Opal Color Manual IHC staining Kit for multiplex immunofluorescence staining measurement. Western blot detected the expression of Nrf2, OCLN, and CLDN5 in murine pulmonary tissues. Results: The results of CT scanning and routine histological measurements showed that APN could protect mice against murine pulmonary injury caused by CA-CPR-ROSC, compared to that of mice in CA-CPR-ROSC group. The results of western blot suggested that the expression of Nrf2 significantly increased in mice pulmonary tissues in CA-CPR-ROSC, whereas the expression of OCLN and CLDN5 obviously decreased in murine pulmonary tissues in CA-CPR-ROSC. Conclusion: Current study indicated the protect role of Adiponectin against acute murine pulmonary injury caused by CA-CPR-ROSC. The protective role of Adiponectin against acute murine pulmonary injury caused by CA-CPR-ROSC might be associated to the Nrf2 signaling pathway.

The protective role of adiponectin in restoring spermatogenesis in mice fed on methionine-choline deficient diet

Introduction and Aim: The process of spermatogenesis requires a continuous supply of nutrients for producing normal sperms. Methionine and choline are considered important amino acids in transport of energy substrates, redox balance, and in DNA methylation while the protein adiponectin is known for its anti-inflammatory and anti-apoptotic function. In this study, we aimed to investigate the effect of methionine and choline on mice testis when fed with a methionine choline deficient diet (MCDD) as well as the protective effect of adiponectin on mice testis. Materials and Methods: This study comprised of 25 mice, which were divided into three groups: Control (n=5); M1 (n=10 that were fed with MCDD for three weeks) and M2 (n=10 that were fed with MCDD for three weeks and in the third week were administered with daily injections of adiponectin for one week). Results: The present study revealed MCDD caused a significant reduction in body weight and increase in the incidence of apoptosis where P value was 0.001; caspase-3 expression was higher than that of Bcl2 in group M1. Adiponectin therapy in the last week showed the potential to restore body weight, reduce apoptotic rate, and the expression of Bcl2 which was higher than that of caspase-3. Conclusion: A diet lacking in methionine and choline not only significantly reduced body weight in mice, but also increased the apoptosis rate of spermatogenic cells. Adiponectin therapy in MCDD fed mice reduced the apoptotic rate and restored spermatogenesis.

Adiponectin accumulation in the retinal vascular endothelium and its possible role in preventing early diabetic microvascular damage

Adiponectin (APN), a protein abundantly secreted from adipocytes, has been reported to possess beneficial effects on cardiovascular diseases in association with its accumulation on target organs and cells by binding to T-cadherin. However, little is known about the role of APN in the development of diabetic microvascular complications, such as diabetic retinopathy (DR). Here we investigated the impact of APN on the progression of early retinal vascular damage using a streptozotocin (STZ)-induced diabetic mouse model. Our immunofluorescence results clearly showed T-cadherin-dependent localization of APN in the vascular endothelium of retinal arterioles, which was progressively decreased during the course of diabetes. Such reduction of retinal APN accompanied the early features of DR, represented by increased vascular permeability, and was prevented by glucose-lowering therapy with dapagliflozin, a selective sodium-glucose co-transporter 2 inhibitor. In addition, APN deficiency resulted in severe vascular permeability under relatively short-term hyperglycemia, together with a significant increase in vascular cellular adhesion molecule-1 (VCAM-1) and a reduction in claudin-5 in the retinal endothelium. The present study demonstrated a possible protective role of APN against the development of DR.

Adiponectin protects obesity-related glomerulopathy by inhibiting ROS/NF-\u03baB/NLRP3 inflammation pathway

BackgroundAdiponectin is an adipocytokine that plays a key regulatory role in glucose and lipid metabolism in obesity. The prevalence of obesity has led to an increase in the incidence of obesity-related glomerulopathy (ORG). This study aimed to identify the protective role of adiponectin in ORG.MethodsSmall-interfering RNA (siRNA) against the gene encoding adiponectin was transfected into podocytes. The oxidative stress level was determined using a fluorometric assay. Apoptosis was analyzed by flow cytometry. The expressions of podocyte markers and pyrin domain containing protein 3 (NLRP3) inflammasome-related proteins were measured by qRT-PCR, immunohistochemistry, and Western blot.ResultsPodocytes treated with palmitic acid (PA) showed downregulated expressions of podocyte markers, increased apoptosis, upregulated levels of NLRP3 inflammasome-related proteins, increased production of inflammatory cytokines (IL-18 and IL-1β), and induced activation of NF-κB as compared to the vehicle-treated controls. Decreased adiponectin expression was observed in the serum samples from high fat diet (HFD)-fed mice. Decreased podocin expression and upregulated NLRP3 expression were observed in the kidney samples from high fat diet (HFD)-fed mice. Treatment with adiponectin or the NLRP3 inflammasome inhibitor, MCC950, protected cultured podocytes against podocyte apoptosis and inflammation. Treatment with adiponectin protected mouse kidney tissues against decreased podocin expression and upregulated NLRP3 expression. The knockout of adiponectin gene by siRNA increased ROS production, resulting in the activation of NLRP3 inflammasome and the phosphorylation of NF-κB in podocytes. Pyrrolidine dithiocarbamate, an NF-κB inhibitor, prevented adiponectin from ameliorating FFA-induced podocyte injury and NLRP3 activation.ConclusionsOur study showed that adiponectin ameliorated PA-induced podocyte injury in vitro and HFD-induced injury in vivo via inhibiting the ROS/NF-κB/NLRP3 pathway. These data suggest the potential use of adiponectin for the prevention and treatment of ORG.

Protective role of adiponectin against testicular impairment in high-fat diet/streptozotocin-induced type 2 diabetic mice

Type 2 diabetes (T2D) is the most common endocrine and metabolic disorder, leading to reproductive impairments and infertility in male. Our recent study showed crucial role of adiponectin in the regulation of testicular functions, and the circulating level of adiponectin declines in diabetes. The current study thus aimed to examine the efficacy of adiponectin in improving testicular dysfunction in high-fat diet/streptozotocin-induced T2D mice. T2D was induced in pre-pubertal mice fed with high-fat diet for ∼10 weeks followed by a single dose of streptozotocin. T2D mice showed presence of increased body mass, hyperglycemia, hyperinsulinemia, insulin resistance, increased oxidative stress, and declined serum testosterone compared to vehicle-treated control mice. The spermatogenic, steroidogenic, metabolic, and antioxidative parameters were evaluated in T2D mice treated with adiponectin for both two and four weeks. The exogenous administration of adiponectin to T2D mice showed enhanced serum testosterone and expression of testicular steroidogenic markers proteins, insulin receptor and GLUT8 proteins, increase in intra-testicular concentrations of glucose and lactate and activity of LDH and antioxidant enzymes compared to the levels in untreated T2D mice. This suggests that treatment of adiponectin effectively improves testicular functions by increasing expression of insulin receptor-mediated increased transport of energy substrate (glucose and lactate) and a marked reduction in oxidative stress are the possible mechanism by which adiponectin effectively improves testicular function in T2D mice.

Adiponectin Suppresses Human Pancreatic Cancer Growth through Attenuating the β-Catenin Signaling Pathway.

Adipokines are emerging as a link between obesity and obesity-related cancers, including pancreatic cancer. Adiponectin is an abundant adipokine with pleiotropic beneficial roles in metabolic disorders. Low adiponectin levels are commonly observed in human obesity and have been associated with increased pancreatic cancer risk in prospective epidemiologic studies. Here, we investigated the direct effect of adiponectin on human pancreatic cancer in vitro and in vivo. Our results showed that adiponectin treatment significantly inhibited the proliferation of human pancreatic cancer cells. Knockdown of adiponectin receptors completely eliminated the antiproliferation effect of adiponectin and markedly promoted the growth of human pancreatic cancer xenografts in nude mice. Further analysis revealed that adiponectin blocked the phosphorylation/inactivation of GSK-3β, suppressed the intracellular accumulation of β-catenin, reduced the expression of cyclin D1, and consequently caused cell cycle accumulation at the G0-G1 phase in pancreatic cancer cells. Adiponectin-mediated attenuation of cell proliferation was abrogated by the GSK-3β inhibitor. In addition, a microarray analysis revealed that adiponectin also downregulated the expression of TCF7L2, a coactivator of β-catenin, at the transcriptional level in pancreatic cancer cells. These results indicated that the protective role of adiponectin against human pancreatic cancer might be attributed to its attenuating effect on the β-catenin signaling pathway. Taken together, our findings support a causal link between hypoadiponectinemia and increased pancreatic cancer risk, and suggest that activating adiponectin signaling could be a novel therapeutic strategy for obesity-related pancreatic cancer.

Inflammation and Vascular Calcification Causing Effects of Oxidized HDL are Attenuated by Adiponectin in Human Vascular Smooth Muscle Cells.

The role of oxidized high- density lipoprotein (oxHDL) and the protective effects of adiponectin in terms of vascular calcification is not well-established. This study was conducted to investigate the effects of oxHDL with regard to inflammation and vascular calcification and to determine the protective role of adiponectin in attenuating the detrimental effects of oxHDL. Cell viability, mineralization, and calcification assays were conducted to optimize the concentration of oxHDL. Then, human vascular smooth muscle cells (HAoVSMCs) were incubated with β-glycerophosphate, HDL, oxHDL, adiponectin, or the combination of oxHDL with adiponectin for 24 h. Protein expression of IL-6, TNF-α, osterix, RUNX2, ALP, type 1 collagen, osteopontin, osteocalcin, WNT-5a, NF-ĸβ(p65), cAMP and STAT-3 were measured by ELISA kits. OxHDL induced vascular calcification by promoting the formation of mineralization nodules and calcium deposits in HAoVSMCs. This was accompanied by an increased secretion of IL-6, osterix, WNT-5a and NF-ĸβ (p65). Interestingly, these detrimental effects of oxHDL were suppressed by adiponectin. Besides, incubation of adiponectin alone on HAoVSMCs showed a reduction of inflammatory cytokines, osteoblastic markers (RUNX2, osterix and osteopontin), WNT-5a and NF-ĸβ (p65). This study exhibits the ability of oxHDL in inducing inflammation and vascular calcification and these detrimental effects of oxHDL can be attenuated by adiponectin.

High adiponectin levels in lean Arab women compared to Asian women.

Adiponectin has been recognized as a potent regulator of metabolism possessing anti-inflammatory and anti-atherogenic functions and inversely associated with increasing incidents of type 2 diabetes and obesity. In this study, we investigated the changes in adiponectin level of 193 Arab and 132 Asian women were compared. Overall, Arab women had statistically significant higher levels of adiponectin 17.84 (1.047) μg/mL than Asians 12.87 (1.049) μg/mL. In conclusion, our data demonstrates that Arab women poses high adiponectin level compared to Asians and the protective role of adiponectin in Arab women against metabolic disorders requires further attention.

A study on rat cardiovascular injury induced by intermittent hypoxia and the protective role of adiponectin

To observe the effect of chronic intermittent hypoxia (CIH) on rat cardiac function and blood pressure, and the protective role of adiponectin (Ad). A total of 24 male Wistar rats were randomly and equally divided into 3 groups: normal control group (NC group), chronic intermittent hypoxygen group (CIH group) and CIH+Ad group. Normal air breathing for NC group and CHI for CIH and CIH+Ad groups were conducted for 28 days. In addition, rats in CIH+Ad group were given intravenous adiponectin at a dosage of 20 µg each time, once a week for successive 4 weeks. The results of echocardiography, blood pressure, plasma adiponectin, endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) were compared among the three groups after 28 days. HE stain showed that the myocardial cells of CIH rats were damaged by CIH. Compared with NC group, rats in CIH group presented with a greater heart/body weight ratio (0.070 ± 0.008 vs. 0.057 ± 0.009, P < 0.05) and systolic blood pressure [(132 ± 4) vs. (123 ± 6) mmHg(1 mmHg = 0.133 kPa), P < 0.05] and a lower LVEF [(70.3 ± 4.1)% vs. (84.1 ± 2.5)%, P < 0.05]. Plasma ET-1 was increased while NO(-)(2)/NO(-)(3) and eNOS decreased in CIH group, compared with NC group [(26.2 ± 6.9) ng/L vs. (7.7 ± 2.7) ng/L, (37 ± 9) µmol/L vs. (65 ± 10) µmol/L, (18 ± 5)µg/L vs. (27 ± 6) µg/L, respectively; P < 0.05]. The heart/body weight ratio, blood pressure and LVEF were improved in CIH+Ad group compared with those in CIH group [0.064 ± 0.009 vs. 0.070 ± 0.008, (127 ± 6) mmHg vs. (132 ± 4) mmHg, P > 0.05; (79 ± 7)% vs. (70 ± 4)%, P < 0.05; respectively]. Plasma ET-1 levels in CIH+Ad and CIH groups showed no significant difference, but were significantly lower in NC group. However, rats in CIH+Ad group had a higher NO(-)(2)/NO(-)(3) level than that in CIH group. Bivariate Correlations showed that NO(-)(2)/NO(-)(3) and eNOS were negatively correlated with systolic blood pressure while heart/body weight ratio, LVEDs, ET-1 and NO(-)(2)/NO(-)(3) were negatively correlated with left ventricular ejection fraction. Through xidative stress, ET-1 and NO imbalance and impaired vascular endothelial function, cardiac function could be damaged by CIH in rats, while supplement of extrinsic adiponectin could improve these damages.

Adiponectin Protects Rat Myocardium against Chronic Intermittent Hypoxia-Induced Injury via Inhibition of Endoplasmic Reticulum Stress

Obstructive sleep apnea syndrome (OSAS) is associated with many cardiovascular disorders such as heart failure, hypertension, atherosclerosis, and arrhythmia and so on. Of the many associated factors, chronic intermittent hypoxia (CIH) in particular is the primary player in OSAS. To assess the effects of CIH on cardiac function secondary to OSAS, we established a model to study the effects of CIH on Wistar rats. Specifically, we examined the possible underlying cellular mechanisms of hypoxic tissue damage and the possible protective role of adiponectin against hypoxic insults. In the first treatment group, rats were exposed to CIH conditions (nadir O2, 5–6%) for 8 hours/day, for 5 weeks. Subsequent CIH-induced cardiac dysfunction was measured by echocardiograph. Compared with the normal control (NC) group, rats in the CIH-exposed group experienced elevated levels of left ventricular end-systolic dimension and left ventricular end-systolic volume and depressed levels of left ventricular ejection fraction and left ventricular fractional shortening (p<0.05). However, when adiponectin (Ad) was added in CIH + Ad group, we saw a rescue in the elevations of the aforementioned left ventricular function (p<0.05). To assess critical cardiac injury, we detected myocardial apoptosis by Terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) analysis. It was showed that the apoptosis percentage in CIH group (2.948%) was significantly higher than that in NC group (0.4167%) and CIH + Ad group (1.219%) (p<0.05). Protein expressions of cleaved caspase-3, cleaved caspase-9, and cleaved-caspase-12 validated our TUNEL results (p<0.05). Mechanistically, our results demonstrated that the proteins expressed with endoplasmic reticulum stress and the expression of reactive oxygen species (ROS) were significantly elevated under CIH conditions, whereas Ad supplementation partially decreased them. Overall, our results suggested that Ad augmentation could improve CIH-induced left ventricular dysfunction and associated myocardial apoptosis by inhibition of ROS-dependent ER stress.

L’adiponectine : une adipokine anti-carcinogène ?

Adipose tissue has long been considered as an « organ » of energy storage. Although many works had previously identified the secretory nature of adipocyte, it was only in 1994, when the leptin gene was cloned, that adipose tissue earned the status of endocrine tissue. It was the first demonstration that an adipose tissue-derived hormone was able to communicate with the central nervous system to control satiety and energy balance. In fact, it is almost at the same time that another major adipokine produced by adipocytes, adiponectin, has been discovered. It took several years to identify the insulin-sensitizing, anti-inflammatory and anti-atherogenic properties of this hormone. More recently, several epidemiological, genetic and experimental findings suggest an anti-carcinogenic role for adiponectin. In this brief review we will present the arguments supporting a protective role of adiponectin in tumor progression, particularly in the context of breast cancer. Adiponectin deficiency commonly observed in obesity may contribute to the natural history of several cancers, as well as the elevation of leptin and other hormonal disturbances associated with excessive adiposity.

Protective Role of Adiponectin in Cardiovascular Disease

This review focuses on the recent findings that adiponectin plays a significant role of in cardiovascular diseases. Adipose tissue functions as an endocrine organ by secreting adipocytokines that can directly affect nearby or remote organs. Adiponectin is an adipocytokine whose concentration is down-regulated in subjects with obesity-related disorders. Low levels of circulating adiponectin appear to associate with the increased prevalence of obesity-linked diseases including atherosclerosis and ischemic heart disease. A number of experimental studies have shown that adiponectin exerts beneficial effects on the cardiovascular system by directly acting on the component cells in the heart and blood vessels. The cardiovascular protection by adiponectin is mediated through its ability to attenuate inflammatory responses and apoptotic activities in the target organs. Thus, adiponectin could represent a therapeutic target molecule for prevention or treatment of cardiovascular diseases.

Alcohol hepatotoxicity: Kupffer cells surface to the top

In this issue of the Archives of Toxicology, Arthur I. Cederbaum from New York Mount Sinai School of Medicine gives a review on cytokine-mediated hepatotoxicity including a state-of-the-art discussion of the involved signalling pathways (An et al. 2012). A key mechanism of alcoholic liver disease is that ethanol consumption increases levels of gut-derived endotoxins to the portal circulation. As a consequence, Kupffer cells are activated through Toll-like receptors, particularly Toll-like receptor 4 (TLR-4). A well-known consequence of TLR-4-mediated activation of Kupffer cells is secretion of tumour necrosis factor alpha (TNF-a), which mediates inflammation and apoptosis. TNF-a signals through two receptors, TNF-a-R1 and TNF-a-R2, which are expressed at higher levels on the hepatocyte membranes compared to all other (non-parenchymal) liver cell types. Therefore, TNF-a is a prototypical cytokine of the Kupffer cell–hepatocyte axis. Cederbaum discusses a number of further mechanisms relevant to alcoholic liver disease, including IL-8 and IL-18, the protective role of adiponectin, AMP-activated protein kinase and transcription factors regulating lipid synthesis, such as SREBPS and sirtuin 1. Hepatotoxicity remains a major reason for drug withdrawal from clinical use (Hewitt et al. 2007; Knobeloch et al. 2012). Therefore, a lot of energy is currently invested into development and improvement of hepatocyte in vitro systems to predict hepatotoxicity (De Kock et al. 2011; Wobus and Loser 2011; Heise et al. 2012; Zellmer et al. 2010; Godoy et al. 2009, 2010a, b; Schumann et al. 2009). However, one of the critical aspects highlighted in the article of Arthur Cederbaum is that hepatocytes may not be the primary ‘sensor’ of hepatotoxicity, but rather react to cytokines released from Kupffer cells. Similar constellations have been reported for other non-parenchymal liver cells, such as sinusoidal endothelial cells and stellate cells (Hoehme et al. 2010; Ding et al. 2010). One of the merits of the current review (An et al. 2012) is that it highlights the role of cell–cell communication between non-parenchymal cells and hepatocytes. The article is a must-read for anyone interested in mechanisms of hepatotoxicity.

Protective role of adiponectin against ethanol-induced gastric injury in mice

Adiponectin is an anti-inflammatory molecule released from adipocytes, and serum adiponectin concentrations are reduced in obesity. We previously reported that gastric erosion occurs in association with obesity and low serum adiponectin levels. In the present study, we examined adiponectin-knockout (APN-KO) mice to elucidate the role of adiponectin in gastric mucosal injury. Gastric injury was induced by oral administration of ethanol in wild-type (WT) and APN-KO mice. Ethanol treatment induced severe gastric injury in APN-KO mice compared with WT mice. In APN-KO mice, increased apoptotic cells and decreased expression of prostaglandin E(2) (PGE(2)) were detected in the injured stomach. We next assessed the effect of adiponectin on the cellular response to ethanol treatment and wound repair in rat gastric mucosal cells (RGM1). Adiponectin induced the expression of PGE(2) and cyclooxygenase 2 (COX-2) in ethanol-treated RGM1 cells. RGM1 cells exhibited efficient wound repair accompanied by increased PGE(2) expression in the presence of adiponectin. Coadministration of adiponectin with celecoxib, a COX-2 inhibitor, inhibited efficient wound repair. These findings indicate that adiponectin has a protective role against ethanol-induced gastric mucosal injury in mice. This effect may be partially mediated by the efficient wound repair of epithelial cells via increased PGE(2) expression.

Protective Role of Adiponectin Against Ethanol Induced Gastric Injury in Mice

19 Adiponectin is an anti-inflammatory molecule released from adipocytes, and serum adiponectin 20 concentrations are reduced in obesity. We previously reported that gastric erosion occurs in 21 association with obesity and low serum adiponectin levels. In the present study, we examined 22 adiponectin-knockout (APN-KO) mice to elucidate the role of adiponectin in gastric mucosal 23 injury. Gastric injury was induced by oral administration of ethanol in wild-type (WT) and 24 APN-KO mice. Ethanol treatment induced severe gastric injury in APN-KO mice compared with 25 WT mice. In APN-KO mice, increased apoptotic cells and decreased expression of prostaglandin 26 E2 (PGE2) were detected in the injured stomach. We next assessed the effect of adiponectin on 27 the cellular response to ethanol treatment and wound repair in rat gastric mucosal cells (RGM1). 28 Adiponectin induced the expression of PGE2 and cyclooxygenase 2 (COX-2) in ethanol-treated 29 RGM1 cells. RGM1 cells exhibited efficient wound repair accompanied by increased PGE2 30 expression in the presence of adiponectin. Co-administration of adiponectin with celecoxib, a 31 COX-2 inhibitor, inhibited efficient wound repair. These findings indicate that adiponectin has a 32 protective role against ethanol-induced gastric mucosal injury in mice. This effect may be 33 partially mediated by the efficient wound repair of epithelial cells via increased PGE2 expression. 34 35

Protective role of adiponectin on endothelial dysfunction induced by AGEs: A clinical and experimental approach

Objective Obesity is characterized by low levels of adiponectin, an adipocytes derived hormone, and by an inflammatory component. Endothelial dysfunction is often found in overweight/obesity, diabetes, and atherosclerosis. Advanced glycation end products (AGEs) induce endothelial dysfunction and are linked to diabetes and increased atherogenicity and inflammation. The aim of the study was to investigate the possible link between adiponectin and N(epsilon)-(carboxymethyl) lysine (CML), the predominant adduct of circulating AGEs in overweight patients, and, in an in vitro model, to test the hypothesis that adiponectin acts as modulator of endothelial dysfunction, induced by AGEs. Results In 108 overweight patients, plasma levels of CML correlated inversely with adiponectin levels. Pre-incubation of human vein endothelial cells (HUVECs) with physiological concentrations of adiponectin, followed by stimulation with AGEs, reduced vascular adhesion molecule-1 (VCAM-1) and E-selectin expression, as assessed by surface enzyme immunoassay. Conclusions Taken together, these findings demonstrate an inverse correlation between CML and adiponectin levels in overweight patients and a protective role of adiponectin on endothelial dysfunction induced by AGEs, suggesting its key role in the treatment of the vascular complications of obesity/metabolic syndrome.

The protective role of adiponectin in pulmonary vascular disease

adiponectin (APN), a 30-kDa multimeric protein exclusively produced by fat cells, reverses insulin resistance (IR) and is independently associated with a reduced risk of type 2 diabetes in apparently healthy individuals ([10][1]). However, in IR states such as obesity and type 2 diabetes, its

Circulating adiponectin levels in relation to melanoma: A case–control study

Aim Melanoma, a malignancy with steadily increasing prevalence, has been associated not only with sun exposure but also with phenotypic characteristics including obesity. Adiponectin, an adipocyte secreted endogenous insulin sensitizer, has been found to play a protective role in several obesity related cancers but has not yet been studied in relation to melanoma. We investigated the association of circulating adiponectin levels with melanoma in Greece, a country with rather low incidence of the disease and high annual sunshine levels. Methods In the context of a case–control study, we studied over a 22-month period 55 patients with incident, histologically confirmed melanoma cases and 165 healthy controls matched for gender and age. Results After controlling for the possible confounding effect of education, body mass index and waist-to-hip ratio in multiple logistic regression analyses, sun sensitive skin type was significantly and positively associated with melanoma risk (OR: 2.48, 95% Confidence Interval: 1.22–5.10, p: 0.01). On the contrary, there was a sizeable, though non-significant, inverse association of serum adiponectin levels with the disease (OR: 0.75, 95% Confidence Interval: 0.52–1.10, p: 0.14). Conclusion A protective role of adiponectin in the development of melanoma cannot be excluded given the presented empirical evidence (25% reduction per one SD of adiponectin) and the direct anti-neoplastic features of the hormone. The results are intriguing enough to point to the need for further investigation.

Adiponectin Deficiency Protects Mice From Chemically Induced Colonic Inflammation

Adiponectin (APN) is an adipokine that regulates insulin sensitivity and is anti-inflammatory in atherosclerosis. The goal of this study was to investigate the role of APN in intestinal inflammation. APN knockout (KO) mice and their wild-type (WT) littermates received dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) to induce intestinal inflammation. Clinical and histologic scores and proliferation of epithelial cells were assessed. Cytokines and APN levels were measured. Expression of APN and heparin binding epidermal growth factor (HB-EGF) was analyzed by immunohistochemistry. Expression of APN and its receptors, HB-EGF, and basic fibroblast growth factor (bFGF) messenger RNA was assessed by reverse-transcription polymerase chain reaction. Association of serum APN with HB-EGF and bFGF was studied by coimmunoprecipitation. APN KO mice are protected from chemically induced colitis; administration of APN restores inflammation. APN is expressed in the colon, luminal APN associates with colonic epithelial cells. In vitro, APN increases production of proinflammatory cytokines from colonic tissue. Expression of colonic APN overlaps with that of bFGF and HB-EGF, which play a protective role in colitis. Circulating APN binds to bFGF and HB-EGF, likely inhibiting their protective activity. Inhibition of EGF receptor signaling, which is required for biologic activity of HB-EGF, restores inflammation in APN KO mice. APN deficiency is associated with protection from chemically induced colitis. APN exerts proinflammatory activities in the colon by inducing production of proinflammatory cytokines and inhibiting bioactivity of protective growth factors. Thus, in colitis, APN exerts an opposite role compared with atherosclerosis.