Expression Of Adiponectin Receptors Research Articles

Senescence and adiponectin signaling — Studies in canine testis

BackgroundThe meaning of senescence for tissue physiological and pathological conditions is poorly known. Based on initial reports especially proteins and mechanisms that regulate this process are necessary to be determinate. MethodsThe main aim of the study was to investigate the presence of senescent cells in canine testicular tissue (mixed breed testes; n = 60) in relation to adiponectin signaling. In detail, new information on the senescence cell number, as well as senescence and adiponectin signaling mechanisms in cryptorchid and germ cell tumor testes were provided with the use of immunohistochemical and colorimetric analyses. ResultsComparison of immunohistochemical results, in cryptorchid and tumor testes revealed increased number of senescent cells (p16 and γH2AX markers). Increased expression of adiponectin and adiponectin receptor 1, as well as extracellular signal-activated kinase (ERK1/2) in pathological testes were detected. In addition, decreased cholesterol and increased testosterone levels in tumor testis were found. ConclusionThe present study is the first to demonstrate the presence as well as the differences that exist in senecent cell number in mixed breed dog testes with cryptorchidism and germ cell tumor. Altered expression of adiponectin signaling and ERK1/2 signaling pathways together with altered cholesterol and testosterone levels reflect important senescence role in disturbed functions of canine testis. Moreover, the application of studied here senescence regulating molecules for detection and prevention against pathologies of the male gonad should be furtherly considered.

AdipoRon Protects against Tubular Injury in Diabetic Nephropathy by Inhibiting Endoplasmic Reticulum Stress.

Endoplasmic reticulum (ER) stress has been reported to play a pivotal role in diabetic nephropathy (DN). AdipoRon is a newly developed adiponectin receptor agonist that provides beneficial effects for diabetic mice; however, its underlying mechanism remains to be delineated. Here, we demonstrated increased expression levels of ER stress markers, accompanied by upregulated levels of proinflammatory cytokines and increased expression of collagen I, fibronectin, Bax, and cleaved caspase 3 in the kidneys of db/db mice compared with control mice. Decreased expression of adiponectin receptor 1 (AdipoR1) and phosphorylated 5′AMP-activated kinase (p-AMPK) was also observed in the kidneys of db/db mice. However, these alterations were partially reversed by intragastric gavage with AdipoRon. In vitro, AdipoRon alleviated high-glucose-induced ER stress, oxidative stress, and apoptosis in HK-2 cells, a human tubular cell line. Moreover, AdipoRon restored the expression of AdipoR1 and p-AMPK in HK-2 cells exposed to high-glucose conditions. Additionally, these effects were partially abrogated by pretreatment with AdipoR1 siRNA, but this abrogation was ameliorated by cotreatment with AICAR, an AMPK activator. Furthermore, the effects of AdipoRon were also partially abolished by cotreatment with compound C. Together, these results suggest that AdipoRon exerts favorable effects on diabetes-induced tubular injury in DN by inhibiting ER stress mediated by the AdipoR1/p-AMPK pathway.

Sex- and season-dependent differences in the expression of adiponectin and adiponectin receptors (AdipoR1 and AdipoR2) in the hypothalamic-pituitary-adrenal axis of the Eurasian beaver (Castor fiber L.)

Adiponectin, a product of the Adipoq gene, is an adipocyte-derived protein hormone of the cytokine family and the most abundantly expressed adipokine. Adiponectin and its receptors AdipoR1 and AdipoR2 (collectively referred to as the adiponectin system) are widely expressed in the central nervous system and other tissues, which suggests that this hormone has pleiotropic effects. Adiponectin could also play a role in the modulation of the hypothalamic–pituitaryadrenal (HPA) hormonal regulatory axis. There is a general scarcity of data on the adiponectin system in wild animals where annual changes in reproductive activity are linked with fluctuations in the activity of the HPA axis. The Eurasian beaver (Castor fiber L.) could be an interesting and suitable model for investigating the above processes. We hypothesized that the expression of the adiponectin system in the tissues of the beaver HPA axis is sex- and season-dependent. The study was performed on adult animals harvested during three different stages of reproductive activity: April (‘breeding’), July (‘post-breeding’) and November (‘pre-breeding’). The expression of the adiponectin system was confirmed in all branches (mediobasal hypothalamus, pituitary, adrenal cortex) of the HPA axis in both sexes and during all periods of reproductive activity. The expression of Adipoq, AdipoR1 and AdipoR2 was generally dependent on sex and the period of the reproductive season. The expression of adiponectin system genes was particularly pronounced in the adrenal cortex. These findings suggest that the adiponectin system in the Eurasian beaver could link reproductive processes with stress responses and energy metabolism.

Altered Brain Adiponectin Receptor Expression in the 5XFAD Mouse Model of Alzheimer's Disease.

Metabolic syndromes share common pathologies with Alzheimer’s disease (AD). Adiponectin, an adipocyte-derived protein, regulates energy metabolism via its receptors, AdipoR1 and AdipoR2. To investigate the distribution of adiponectin receptors (AdipoRs) in Alzheimer’s, we examined their expression in the aged 5XFAD mouse model of AD. In age-matched wild-type mice, we observed neuronal expression of both ARs throughout the brain as well as endothelial expression of AdipoR1. The pattern of receptor expression in the aged 5XFAD brain was significantly perturbed. Here, we observed decreased neuronal expression of both ARs and decreased endothelial expression of AdipoR1, but robust expression of AdipoR2 in activated astrocytes. We also observed AdipoR2-expressing astrocytes in the dorsomedial hypothalamic and thalamic mediodorsal nuclei, suggesting the possibility that astrocytes utilise AdipoR2 signalling to fuel their activated state in the AD brain. These findings provide further evidence of a metabolic disturbance and demonstrate a potential shift in energy utilisation in the AD brain, supporting imaging studies performed in AD patients.

Vascular Protection by Exercise in Obesity: Inflammasome-associated Mechanisms.

The nodlike receptor family pyrin domain containing 3 (NLRP3) inflammasome is a critical player in vascular pathology as it regulates caspase-1-mediated interleukin (IL)-1β processing. Physical activity ameliorates obesity-induced inflammation and vascular dysfunction, but the mechanisms responsible for these positive changes are incompletely understood. Here, the protective effect of physical activity on the inflammasome-associated vascular dysfunction in obesity and its putative mechanisms were investigated. Mice were fed a control low-fat diet (LFD) or a high-fat diet (HFD; 45% of calories from fat) and provided with running wheel access (LF-RUN or HF-RUN) or denied wheel access for our sedentary condition (LF-SED or HF-SED). The NLRP3 inflammasome-associated pathway, including NLRP3, caspase-1, and IL-1β, in mice aorta was examined by RT-qPCR and FLICA and DAB staining. The protein expression of zonula occluden-1 (ZO-1), ZO-2, adiponectin (APN), and adiponectin receptor 1 (AdipoR1) in aortic endothelial cells was determined by immunofluorescence double staining. Intracellular reactive oxidative stress and nitric oxide (NO) production were monitored with fluorescence probes, dihydroethidium, and diaminofluorecein. HFD increased caspase-1 and IL-1β at mRNA and protein levels in endothelial cells of the aorta, and this was attenuated by voluntary running. HFD decreased ZO-1 and ZO-2 expression and reduced APN and AdipoR1 signaling; these were restored by running. The elevated intracellular superoxide (O2) production observed in HF-SED was ameliorated in HF-RUN. Finally, HF-RUN improved NO production in the aorta compared with HF-SED. Our findings suggest that voluntary running ameliorates mechanisms associated with vascular dysfunction by suppressing NLRP3 inflammasome, improving NO production, and reducing oxidative stress. Such benefits of physical activity may be, at least in part, associated with APN-AdipoR1 signaling and tight junction protein expression.

Effects of glucose, insulin, glucagon, LPS and poly (I:C) on adiponectin receptors expression in grass carp (Ctenophcuyngodon idellus)

Adiponectin plays critical roles in energy metabolism and immunity of mammals by binding to its receptors (AdipoR1 and AdipoR2). However, they have not been fully understood in fish. The present study examined the distribution of adiponectin receptors (AdipoRs) mRNA in grass carp, and the changes of their expressions under glucose load, insulin or glucagon stimulation, lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid [poly (I:C)] challenge. As for glucose load, fish were orally administrated with glucose (1.67 mg/g BW) for 1, 3, 6, 12 h. For insulin or glucagon stimulation, the primary hepatocytes of grass carp were incubated with 0, 10, 100, 1000 nM insulin or glucagon for 1, 3, 6, 12 h. In the immune challenge experiment, grass carp were intraperitoneally injected with LPS or poly (I:C) (5 μg/g BW) for 3, 6, 12, 24, 48 h. Finally, AdipoRs mRNA expression in all experiments was detected by Real-time quantitative PCR. The results showed that AdipoRs mRNA was widely expressed in various tissues of grass carp. The adipoR1a mRNA was highly expressed in the brain regions, and the highest level of adipoR2 mRNA was observed in the adipose tissue. Glucose load up-regulated adipoR1b and adipoR2 mRNA expressions in the liver at 6 h post administration and decreased adipoR1a expression in the muscle at 3 h. Insulin significantly enhanced adipoR1b and adipoR2 mRNA expressions in the hepatocytes at 1–12 h, and promoted adipoR1a mRNA expression at 1, 3 and 12 h, while glucagon had little effect on their expressions. LPS and poly (I:C) stimuli induced AdipoRs expression in the liver at 6 and 12 h, and their expressions in the muscle were decreased slightly or remained unchanged. In addition, LPS promoted AdipoRs expression in the kidney and spleen, whereas poly (I:C) only induced adipoR1a mRNA expression in the kidney, and increased adipoR2 mRNA level in the spleen. These results suggest that AdipoRs may act as one of the targets of insulin and immune response in grass carp, but whether they are direct target remains to be further studied.

The protective effect of recombinant globular adiponectin on testis by modulating autophagy, endoplasmic reticulum stress and oxidative stress in streptozotocin-induced diabetic mice

This study was to investigate whether recombinant globular adiponectin produced its protective effect on the testis of diabetic mice by modulating autophagy, endoplasmic reticulum stress and oxidative stress. Male mice were randomly divided into control, diabetic, diabetic treated with low and high dose of adiponectin. Mice were killed at the termination after 4 weeks and 8 weeks of adiponectin treatment. Serum levels of glucose, lipids, testosterone, insulin, LH and FSH were measured. The protein expression of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), Caspase12, Beclin1, microtubule-associated protein light chain 3 (LC3) and p62 was determined by western blotting. The mRNA expression of adiponectin receptor 1 (AdipoR1), p22phox, p47phox, nuclear factor erythroid2-related factor 2 (Nrf2), NAD(P)H-quinone oxidoreductase 1(NQO1), heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) were determined by real-time fluorescence quantitative PCR. The testicular weight, the sperm number and motility, and the serum levels of testosterone and insulin were significantly decreased in diabetic mice (P < 0.05). The expression of Beclin1, LC3, Nrf2, NQO1, HO-1, SOD and AdipoR1 were significantly decreased (P < 0.05), while the expression of GRP78, CHOP, Caspase12, p62, p22phox and p47phox were notably increased in the testes of diabetic mice (P < 0.05). Adiponectin treatment significantly reversed the above-mentioned changes in the testes of diabetic mice, some of which were dose- and time-dependent (P < 0.05). These data suggested that recombinant globular adiponectin may produce the protective effect on the testes of diabetic mice by inducing autophagy and inhibiting ER stress and oxidative stress.

Ghrelin antagonist regulates metabolic hormone receptorsin the hypothalamus of ewes

Abstract This study evaluates the effects of ghrelin antagonist on mRNA abundance for metabolic hormone receptors in feed-restricted ewes. Ewes were randomly assigned to one of three treatments; Control (CO): feed above maintenance energy intake requirements and daily subcutaneous saline infusion; Feed restriction (FR): feed restricted and daily subcutaneous saline infusion; Ghrelin antagonist (GA): feed restricted and daily subcutaneous of 7.5 μg/kg of d -Lys3-GHRP-6. Blood was sampled on days 1, 4, 9, and 13, relative to the start of the experiment, to quantify plasma glucose, NEFA and ghrelin concentrations. At day 13, the hypothalamus was collected to evaluate relative mRNA expression. The CO ewes had lesser plasma NEFA concentration compared with FR and GA ewes. There was a treatment by time interaction for plasma glucose concentration, all treatment started with similar plasma glucose concentration, but at day 13 CO ewes had a greater plasma concentration than FR and GA. Relative mRNA expression for glucagon receptor in GA ewes tended to be lesser compared with CO and FR treated ewes. There were no differences in insulin receptor mRNA relative expression between the groups. Ghrelin receptor mRNA relative expression tended to be greater in the GA compared with the CO treated ewes. There was no effect of GA on leptin receptors. However, there was a tendency toward greater relative expression of leptin receptor mRNA in the FR compared with the CO ewes. Relative expression of adiponectin receptor mRNA was lesser in the GA compared with CO and FR ewes. Cortisol receptor relative mRNA expression was greater in the FR compared with the CO ewes. Restricting dietary intake of ewes change mRNA relative expression of cortisol and leptin receptors in the hypothalamus of ewes. These variations are countered with ghrelin antagonist. Ghrelin antagonist modifies the mRNA relative expression of ghrelin, glucagon and adiponectin receptors. These results suggest that ghrelin could regulates metabolic hormone activity by modifying the relative expression of their receptors mRNA.

CoQ10 exerts hepatoprotective effect in fructose-induced fatty liver model in rats.

Excess dietary sugar is associated with deleterious metabolic effects, liver injury, and coenzyme-Q10 (CoQ10) deficiency. This study investigates the ability of CoQ10 to protect against fructose-induced hepatic damage. Rats were fed tap water or 30% fructose for 12weeks with or without CoQ10 (10mg/kg, po). An additional group of rats were allowed to feed on either water or 30% fructose for 12weeks, followed by four weeks of treatment with either the vehicle or CoQ10. Fructose-fed rats showed lower CoQ10 levels, increased systolic pressure, increased body weight, higher liquid consumption, decreased food intake and hyperglycemia. Fructose-fed rats also showed deteriorated serum and liver lipid profiles, impaired liver function tests and oxidative status, and lower expression of adiponectin receptor 1 and 2 along with higher GLUT-2 levels. Furthermore, following fructose treatment, tyrosine kinase-PI3K pathway was inhibited. Additionally, there was an increase in the levels of apoptotic markers and serum visfatin and a decrease in the levels of adiponectin and soluble receptor of the advanced glycated end product. Consequently, several histopathological changes were detected in the liver. Concurrent or three months post-exposure administration of CoQ10 in fructose rats significantly reversed or attenuated all the measured parameters and hepato-cytoarchitecture alterations. This study suggests CoQ10 supplement as a possible prophylaxis or treatment candidate for fructose-induced liver injury.

Adiponectin stimulates glucose uptake in mouse blastocysts and embryonic carcinoma cells

Preimplantation embryos are sensitive to maternal hormones affecting embryonic signal transduction and metabolic functions. We examined whether adiponectin, the most abundantly secreted adipokine, can influence glucose transport in mouse embryonic cells. In mouse blastocysts full-length adiponectin stimulated glucose uptake, while no effect of globular adiponectin was found. Full-length adiponectin stimulated translocation of GLUT8 glucose transporter to the cell membrane; we did not detect significant changes in the intracellular localization of GLUT4 glucose transporter in adiponectin-treated blastocysts. To study adiponectin signaling in detail, we used embryoid bodies formed from mouse embryonic carcinoma cell (ECC) line P19. We confirmed the expression of adiponectin receptors in these cells. Similar to mouse blastocysts, full-length adiponectin, but not globular adiponectin, stimulated glucose uptake in ECC P19 embryoid bodies. Moreover, full-length adiponectin stimulated AMPK and p38 MAPK phosphorylation. These results indicate that besides AMPK, p38 MAPK is a potential target of adiponectin in mouse embryonic cells. AMPK inhibitor did not influence the adiponectin-stimulated p38 MAPK phosphorylation, indicating independent action of these two signaling pathways. In mouse embryos adiponectin acts as a hormonal regulator of glucose uptake, which becomes especially important in phases with reduced levels of circulating insulin. Our results suggest that adiponectin maintains the glucose supply for early embryos under hypoinsulinaemic conditions, for example, in mothers suffering from type 1 diabetes mellitus.

Tectorigenin attenuates diabetic nephropathy by improving vascular endothelium dysfunction through activating AdipoR1/2 pathway

Diabetic nephropathy (DN), a kind of microvascular complication, is a primary cause of end-stage renal disease worldwide. However, therapeutic drugs for DN treatment are still in lack. The glomerular endothelium is essential to maintain selective permeability of glomerular filtration barrier and glomerular vasculature function. Growing evidences show that endothelial dysfunction or injury is the initial stage of vascular damage in DN, which can be induced by hyperglycemia, lipotoxicity, and inflammation. Therefore, to improve the function of vascular endothelium in kidney is a key point for treatment of DN. As a plant isoflavone, tectorigenin (TEC) has attracted considerable attention due to its anti-proliferative and anti-inflammatory functions. However, whether TEC could inhibit the DN development remains unknown. In this study, we examined the effects of TEC on DN development in db/db mice, a type of genetic defect diabetic mice that can spontaneously develop into severe renal dysfunction. Intriguingly, TEC treatment restored diabetes-induced glucose and lipid metabolic disorder; and improved the deterioration of renal function, particularly the renal endothelium function in db/db mice. Additionally, TEC inhibited the renal inflammation via reducing macrophages infiltration and M1 polarization. Moreover, TEC inhibited lipopolysaccharide (LPS)-induced endothelial injury and M1 polarization in vitro. Mechanistically, TEC partially restored the reduction in expression of adiponectin receptor 1/2 (AdipoR1/2), pi-LKB1, pi-AMPKα, and PPARα in vitro and in vivo. Noteworthy, these beneficial pharmacological activities mediated by TEC were significantly attenuated after AdipoR1/2 knockdown by siRNA, indicating that AdipoR1/2 plays a critical role in protection against DN. Collectively, these results suggested that TEC have a potently effect for retarding type 2 diabetes–associated DN.

Adiponectin inhibits the differentiation and maturation of osteoclasts via the mTOR pathway in multiple myeloma.

The present study sought to investigate the correlation between adipose cytokines (visfatin, leptin and adiponectin) and markers of multiple myeloma bone disease, and to determine the effects and mechanism of action of adiponectin on the differentiation and maturation of osteoclasts in multiple myeloma (MM). The levels of visfatin, leptin and adiponectin were measured. Their association with the indices of myeloma tumor load and bone disease were analyzed. Reverse transcription-quantitative PCR was used to detect the expression of receptor activator of nuclear factor-κB ligand (RANKL), osteoclast associated Ig-like receptor (OSCAR), tartrate-resistant acid phosphatase (TRAP) and Cathepsin K genes. Flow cytometry was used to detect the expression of adiponectin receptor 1 (AdipoR1) and the phosphorylation of the mechanistic target of rapamycin kinase (mTOR) pathway-associated proteins mTOR and eukaryotic translation initiation factor 4E-binding protein (4EBP1). There were no significant correlations among leptin, visfatin and the indexes of myeloma tumor load and bone disease. Serum adiponectin levels were significantly lower in patients with newly diagnosed multiple myeloma compared with healthy volunteers (12.37±3.13 vs. 13.80±0.95; P<0.05). The number of mature osteoclasts in the adiponectin group was lower compared with in the control group. Adiponectin also inhibited the mRNA expression of the osteoclast-associated factors RANKL, OSCAR, TRAP and Cathepsin K. Comparison between the non-adiponectin group and the adiponectin group revealed that adiponectin increased the expression of AdipoR1 on the surface of osteoclast precursor cells (26.21±4.27% vs. 29.86±6.23%; P<0.05) and reduced the expression of phosphorylated (p-)mTOR (7.89±1.00% vs. 5.91±1.26%; P<0.05) and p-4EBP1 (26.78±5.00% vs. 22.49±4.24%; P<0.05). The p-mTOR and p-4EBP1 levels in the adiponectin + MHY1485 (an mTOR signaling pathway-specific agonist) group were significantly higher compared with those in the adiponectin group. It was revealed that adiponectin may inhibit osteoclast differentiation and maturation via the mTOR pathway. In conclusion, adiponectin inhibits the differentiation and maturation of osteoclasts by increasing the expression of AdipoR1 and reducing the phosphorylation levels of mTOR and 4EBP1 in patients with MM.

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.

The metabolic and vascular protective effects of olive (Olea europaea L.) leaf extract in diet-induced obesity in mice are related to the amelioration of gut microbiota dysbiosis and to its immunomodulatory properties

IntroductionMany studies have showed the beneficial effects of the olive (Olea europaea) leaf extract (OLE) in experimental models of metabolic syndrome, which have been ascribed to the presence of phenolic compounds, like oleuropeoside. This study evaluated the effects of a chemically characterized OLE in high fat diet (HFD)-induced obesity in mice, describing the underlying mechanisms involved in the beneficial effects, with special attention to vascular dysfunction and gut microbiota composition. MethodsC57BL/6J mice were distributed in different groups: control, control-treated, obese and obese-treated with OLE (1, 10 and 25 mg/kg/day). Control mice received a standard diet, whereas obese mice were fed HFD. The treatment was followed for 5 weeks, and animal body weight periodically assessed. At the end of the treatment, metabolic plasma analysis (including lipid profile) as well as glucose and insulin levels were performed. The HFD-induced inflammatory status was studied in liver and fat, by determining the RNA expression of different inflammatory mediators by qPCR; also, different markers of intestinal epithelial barrier function were determined in colonic tissue by qPCR. Additionally, flow cytometry of immune cells from adipose tissue, endothelial dysfunction in aortic rings as well as gut microbiota composition were evaluated. Faecal microbiota transplantation (FMT) to antibiotic-treated mice fed with HFD was performed. ResultsOLE administration reduced body weight gain, basal glycaemia and insulin resistance, and showed improvement in plasma lipid profile when compared with HFD-fed mice. The extract significantly ameliorated the HFD-induced altered expression of key adipogenic genes, like PPARs, adiponectin and leptin receptor, in adipose tissue. Furthermore, the extract reduced the RNA expression of Tnf-α, Il-1β, Il-6 in liver and adipose tissue, thus improving the tissue inflammatory status associated to obesity. The flow cytometry analysis in adipose tissue corroborated these observations. Additionally, the characterization of the colonic microbiota by sequencing showed that OLE administration was able to counteract the dysbiosis associated to obesity. The extract reversed the endothelial dysfunction observed in the aortic rings of obese mice. FMT from donors HFD-OLE to recipient mice fed an HFD prevented the development of obesity, glucose intolerance, insulin resistance and endothelial dysfunction. ConclusionOLE exerts beneficial effects in HFD-induced obesity in mice, which was associated to an improvement in plasma and tissue metabolic profile, inflammatory status, gut microbiota composition and vascular dysfunction.

Effect of moxibustion at "Shenque" (CV8) and "Zusanli" (ST36) on expression of adiponectin and adiponectin receptor in Alzheimer's disease rats

To observe the effect of moxibustion on serum adiponectin content, and expression of adiponectin and adiponectin receptor in adipose tissue in Alzheimer's disease (AD) rats, so as to explore its mechanism underlying improvement of AD. Fifty male SD rats were randomly divided into control, model, Shenque (CV8), Zusanli (ST36) and CV8＋ST36 groups (n＝10 in each group). The AD model was established by intraperitoneal injection of D-galactose (400 mg•kg－1•d－1) for 5 weeks and scopolamine hydrobromide (3 mg •kg－1•d－1) for 2 weeks. Moxibustion was applied to CV8, ST36 and CV8＋ST36 respectively for 3 moxa-cones every time, once daily for 5 weeks. Morris water maze tests were used to assess the rats' learning-memory ability. The contents of serum adiponectin were assayed using ELISA, and the expression of adiponectin and adiponectin receptor in the adipose tissue was detected by quantitative real-time PCR and Western blot, separately. Following modeling, the average escape latency of Morris water maze tests was significantly prolonged (P<0.05), the content of serum adiponectin and the expression level of adiponectin mRNA in adipose tissue were significantly decreased (P<0.01), the expression of adiponectin receptor protein significantly decreased in the model group relevant to the control group (P<0.01). After the intervention, the average escape latency was significantly shortened (P<0.05), the decreased serum adiponectin content and adiponectin mRNA expression, and the decreased adiponectin receptor protein expression in adipose tissue were all reversed in the 3 treatment groups (P<0.01，P<0.05). No significant differences were found among the three moxibustion groups in the above indexes (P>0.05). Moxibustion at CV8, ST36 and CV8＋ST36 is effective in up-regulating serum adiponectin content，adiponectin mRNA expression and adiponectin receptor protein expression in adipose tissue, which may provide evidence for clinical election of acupoints.

Regular Swimming Exercise Attenuated Neuroma Pain in Rats: Involvement of Leptin and Adiponectin

Accumulating evidence demonstrates the beneficial effects of physical exercise on pain conditions; however, the underlying mechanisms are not understood thoroughly. The purpose of the present study was to investigate the effects of regular swimming exercise on neuroma pain and the possible roles of adipokines (leptin and adiponectin) in the pain behaviors modulated by exercise. The results showed that 5 weeks of regular swimming exercise relieved pain behaviors in a rat model of neuroma pain and normalized the dysregulation of circulating leptin and adiponectin in plasma induced by nerve injury. Moreover, regular swimming exercise reversed the altered expressions of leptin receptor and adiponectin receptor 1 in neuroma. In addition, the administration of exogenous leptin to the neuroma site dampened the effects of regular swimming exercise on neuroma pain and adiponectin administration alleviated the neuroma pain in the non-exercised neuroma rats. These findings indicate that leptin and adiponectin might be involved in mediating the beneficial effects of exercise on neuroma pain. PerspectivePerspective: Identifying which endogenous processes are activated by specific exercise regimes would likely reveal novel therapeutic targets for the treatment of neuropathic pain. The current study suggests that adipokines might be involved in pain behaviors modulated by exercise and thus presents them as potential targets for pain management.

Uterine perivascular adipose tissue: A novel regulator of uterine artery hemodynamics during normal pregnancy

IntroductionDuring pregnancy, uterine artery (UtA) blood flow increases compared to non‐pregnant state, in part due to reductions in uterine artery tone. The main objective of this study was to determine the role of adipose tissue surrounding UtA (perivascular adipose tissue, PVAT) in pregnancy‐induced changes in UtA blood flow and vasodilatory capacity. We hypothesized that uterine PVAT augments UtA blood flow and potentiates UtA dilatory responses in pregnant rats. Also, we hypothesized that pregnancy induces distinct changes in uterine PVAT morphology and gene expression as compared to other adipose depots.MethodsBlood flow and vascular reactivity were measured in UtA in pregnant and non‐pregnant rats using transonic perivascular probes and wire myography techniques, respectively. Reactivity to acetylcholine (ACh: induces endothelium‐dependent relaxation, 10−9 – 3×10−5 M) and sodium nitroprusside (SNP: induces endothelium‐independent relaxation, 10−11 – 3×10−5 M) was measured in isolated UtA in the presence and absence of PVAT‐conditioned media (PVATmedia, 30‐min incubation). Adipocyte size was determined in hematoxylin and eosin‐stained sections of uterine PVAT and ovarian adipose tissue. Gene expression was determined in uterine and periaortic PVAT using qRT‐PCR.ResultsMaximum and minimum uterine artery blood flow (UBF) were increased in UtA with intact PVAT compared to PVAT‐denuded UtA from pregnant rats (UBFmax (mL/min); denuded: 1.47 ± 0.3 vs. intact: 2.23 ± 0.2, p = 0.01; UBFmin (mL/min); denuded: 0.71 ± 0.1 vs. intact: 1.16 ± 0.1, p = 0.0002). Uterine PVAT had no effect on UBF in non‐pregnant rats (p&gt;0.9). UtA from pregnant and non‐pregnant rats incubated with PVATmedia had reduced sensitivity to ACh compared to UtA controls [Pregnant, pEC50; −PVATmedia: 7.14 ± 0.1 vs. +PVATmedia: 6.38 ± 0.2, p = 0.0006; Non‐pregnant, pEC50; −PVATmedia: 7.01 ± 0.1 vs. +PVATmedia: 6.50 ± 0.1, p = 0.005). PVATmedia had no effect on UtA sensitivity to SNP in either pregnant (p=0.48) or non‐pregnant rats (p = 0.2). Adipocyte area was greater in ovarian adipose tissue from pregnant compared to nonpregnant rats (Area (μm2/unit cell); Non‐pregnant: 563.6 ± 76.6 vs. Pregnant: 857.6 ± 31.0, p = 0.02) but there were no group differences in uterine PVAT morphology (p = 0.6). Expression of uncoupling protein‐1 (UCP‐1) was downregulated (p = 0.02) in aortic PVAT but was unchanged in uterine PVAT (p = 0.4). Expression of peroxisome proliferator‐activated receptor gamma (PPAR‐γ), adiponectin receptor (AdipoR1), and leptin were downregulated in uterine PVAT (p ≤ 0.02) but not in aortic PVAT (p ≥ 0.6).ConclusionsUterine PVAT plays a regulatory role in uterine artery hemodynamics and reactivity during normal pregnancy and has a distinct and differential gene profile as compared to other perivascular depots. Ongoing studies investigate the effects of pregnancy on cross‐talk between PVAT and maternal uterine arteries.Support or Funding InformationUniversity of North Texas Health Science Center Pilot GrantThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Role of Adiponectin in prostate cancer.

ABSTRACTObesity is defined as a chronic and excessive growth of adipose tissue. It has been associated with a high risk for development and progression of obesity-associated malignancies, while adipokines may mediate this association. Adiponectin is an adipose tissue-derived adipokines, with significant anti-diabetic, anti-inflammatory, anti-atherosclerotic and anti-proliferative properties. Plasma adiponectin levels are decreased in obese individuals, and this feature is closely correlated with development of several metabolic, immunological and neoplastic diseases. Recent studies have shown that prostate cancer patients have lower serum adiponectin levels and decreased expression of adiponectin receptors in tumor tissues, which suggests plasma adiponectin level is a risk factor for prostate cancer. Furthermore, exogenous adiponectin has exhibited therapeutic potential in animal models. In this review, we focus on the potential role of adiponectin and the underlying mechanism of adiponectin in the development and progression of prostate cancer. Exploring the signaling pathways linking adiponectin with tumorigenesis might provide a potential target for therapy.

Expression of adiponectin receptors in the brain of adult zebrafish and mouse: Links with neurogenic niches and brain repair.

Adiponectin and its receptors (adipor) have been initially characterized for their role in lipid and glucose metabolism. More recently, adiponectin signaling was shown to display anti-inflammatory effects and to participate in brain homeostasis and neuroprotection. In this study, we investigated adipor gene expression and its regulation under inflammatory conditions in two complementary models: mouse and zebrafish. We demonstrate that adipor1a, adipor1b, and adipor2 are widely distributed throughout the brain of adult fish, in neurons and also in radial glia, behaving as neural stem cells. We also show that telencephalic injury results in a decrease in adipor gene expression, inhibited by an anti-inflammatory treatment (Dexamethasone). Interestingly, adiponectin injection after brain injury led to a consistent decrease (a) in the recruitment of microglial cells at the lesioned site and (b) in the proliferation of neural progenitors, arguing for a neuroprotective role of adiponectin. In a comparative approach, we investigate Adipor1 and Adipor2 gene distribution in the brain of mice and demonstrated their expression in regions shared with fish including neurogenic regions. We also document Adipor gene expression in mice after middle cerebral artery occlusion and lipopolysaccharide injection. In contrast to zebrafish, these inflammatory stimuli do no impact cerebral adiponectin receptor gene expression in mouse. This work provides new insights regarding adipor expression in the brain of fish, and demonstrates evolutionary conserved distribution of adipor with mouse. This is the first report of adipor expression in adult neural stem cells of fish, suggesting a potential role of adiponectin signaling during vertebrate neurogenesis. It also suggests a potential contribution of inflammation in the regulation of adipor in fish.

Adiponectin deficiency has no effect in murine autoimmune myocarditis

BackgroundAdiponectin is a hormone that together with its receptors modulates a number of metabolic processes including gluconeogenesis and lipid catabolism. It belongs to the C1QTNF (complement C1q tumor necrosis factor-related protein) family, which has a variety of members with high amino acid sequence homology and overlapping functions. Concentration of adiponectin in blood is inversely correlated with body fat percentage and cardiac risk factors like blood pressure and CRP (C-reactive protein) level. Studies have identified the existence of a cardiac adiponectin system. However, little is known about the role of this system in the pathogenesis of autoimmune myocarditis. Thus, we have studied the involvement of adiponectin in the development of this autoimmune disorder in a mouse model of experimental autoimmune myocarditis (EAM). MethodsAdiponectin knockout (ko) and wild type (wt) mice were immunized with cardiac troponin I (cTnI) to induce an EAM. To determine the severity of myocardial damage, inflammation and fibrosis were scored after HE and Afog staining and high sensitivity troponin T (hsTnT) level was measured. To detect if changes in specific inflammatory cell numbers could be observed between the genotypes, we performed immunohistochemical staining to detect T lymphocytes, B lymphocytes and macrophages. The level of the humoral immune response was determined through the measurement of cTnI-specific serum IgG autoantibodies. Relative mRNA expression of different cytokines, C1QTNF family members and adiponectin receptors in the heart tissue was analyzed with qPCR. ResultsAnimals immunized with cTnI developed autoimmune myocarditis with a significant deterioration of cardiac parameters compared to the corresponding control group. The adiponectin ko group immunized with cTnI showed a tendency towards increased inflammation, fibrosis, heart-to-body-weight ratio, infiltration pattern of T lymphocytes, B lymphocytes and macrophages, hsTnT concentration, humoral immune response and mRNA expression of interleukin 6 in the heart tissue and decreased weight gain compared to the wt group immunized with cTnI. However, the difference to the wt group treated with cTnI was not significant. The analysis of cardiac mRNA expression of adiponectin receptors and four C1QTNF family members, most suitable for fulfilling the functions of adiponectin in adiponectin ko mice, did not show any significant differences between adiponectin ko and wt group at all. ConclusionOur study reveals that the absence of adiponectin did not lead to a significantly increased impairment of cardiac function and was also unlikely to be compensated by its receptors or other C1QTNF family members in the murine model of EAM. Here, other synergistic or redundant effects might play a role and must be investigated in further studies to understand the role and function of adiponectin in autoimmune myocarditis.