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ObjectiveTo investigate the effects of Buyang Huanwutang （BYWHT） on reducing inflammatory injury and improving neurological function after cerebral ischemia-reperfusion in rats via activating the adiponectin （APN） pathway. MethodMale SD rats were randomized into sham， model， BYHWT （16 g·kg-1， twice a day）， and BYHWT + APN inhibitor （GW9662） groups. In the sham group， blood vessels were isolated. The rat model of middle cerebral artery occlusion （MCAO） was established. The rats in the BYHWT+GW9662 group was treated with subcutaneous injection of GW9662 at 4 m·kg-1 30 min before MCAO surgery and BYHWT at 16 g·kg-1 by gavage after MCAO surgery， once in the morning and once in the evening. The immunofluorescence （IF） assay was employed to observe the expression of adiponectin receptor 1 （AdipoR1） and the colocalization of AdipoR1 with neuronal nuclei （NeuN） and ionized calcium binding adaptor molecule 1 （Iba1） in the brain. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the expression of APN in the serum and brain. The balance beam test was carried out to examine the balance ability， and the grasping test to assess the recovery of limb strength. The immunofluorescence assay was used to detect the expression of myeloperoxidase （MPO）. Western blot was employed to determine the expression of tumor necrosis factor-alpha （TNF-α）， interleukin （IL）-1β， IL-6， and IL-10 and in the brain. ResultCompared with the sham group， the modeling promoted the expression of AdipoR1 （P<0.01）， lowered the APN levels in the serum and brain （P<0.05， P<0.01）， increased the score in the balance beam test （P<0.01）， and decreased the grasping strength of forepaw （P<0.01）， which were accompanied with increased MPO， TNF-α， IL-1β， and IL-6 levels （P<0.01） and decreased IL-10 level （P<0.01）. Compared with the model group， BYHWT promoted the expression of AdipoR1 （P<0.01）， elevated APN levels in the serum and brain （P<0.05， P<0.01）， and increased the grasping strength of forepaw （P<0.01）， which were accompanied with lowered MPO， TNF-α， IL-1β， and IL-6 levels （P<0.01） and elevated IL-10 level （P<0.01）. All the above effects were partially blocked by GW9662. ConclusionBYHWT can reduce inflammatory injury and improve neurological function in the rat model of cerebral ischemia-reperfusion by activating the APN pathway.
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@#Adiponectin, an adipocytokine secreted by adipocytes, has emerged as a potential treatment agent for type 2 diabetes. Adiponectin plays a variety of physiological roles in regulating glucolipid metabolism, oxidative stress, inflammatory responses and bone metabolism by binding to its receptors expressed on a variety of cells and tissues. Numerous studies have confirmed the strong association of adiponectin with type 2 diabetes-related periodontitis. Adiponectin can improve systemic insulin resistance by increasing insulin sensitivity and promoting insulin secretion. It improves the periodontal inflammatory response by inhibiting the expression of proinflammatory cytokines induced by Porphyromonas gingivalis lipopolysaccharide and promoting M2-type polarization of macrophages. In addition, adiponectin inhibits osteoclast differentiation and maturation through various pathways, such as Wnt/β-catenin and NF-κ, and promotes osteoblast differentiation to regulate bone metabolism, thus improving periodontal bone resorption and destruction. Therefore, adiponectin is expected to become a therapeutic target for type 2 diabetes-related periodontitis. Due to the physiological characteristics of adiponectin, its clinical application has been somewhat limited. This article reviews the latest research progress on adiponectin in type 2 diabetes-related periodontitis, aiming to elucidate the possible effects of adiponectin on type 2 diabetes-related periodontitis in terms of glycemic control, anti-inflammation and bone metabolism and to provide some opinions on the treatment of this disease and the development of relevant drugs.
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This study investigated the effects and mechanisms of 6-gingerol on adipose tissue insulin resistance in naturally aging rats with glycolipid metabolism disorders. Twenty-seven aging male SD rats were randomly divided into a model group(aged, n=9) and two groups treated with 6-gingerol at 0.05 mg·kg~(-1)(G-L, n=9) and 0.2 mg·kg~(-1)(G-H, n=9). Six young rats were randomly assigned to a normal control group(NC). Rats were treated for seven weeks by gavage. Non-esterified fatty acid(NEFA) and insulin content was determined by enzyme-linked immunosorbent assay(ELISA), and adipose tissue insulin resistance index(Adipo-IR) was calculated. HE staining was used to observe the size of adipocytes in epididymal white adipose tissue(eWAT). The gene and protein expression levels of adiponectin receptor 1(AdipoR1), AMP-activated protein kinase α(AMPKα), phosphorylated AMPK(p-AMPKα~(Thr172)), peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α), phosphatidylinositol 3-kinase(PI3 K), protein kinase B(Akt), phosphorylated Akt(p-Akt~(Ser473)), tumor necrosis factor-α(TNF-α), c-Jun N-terminal kinase 1/2(JNK1/2), phosphorylated JNK1/2(p-JNK~(Thr183/Tyr185)), interleukin-1β(IL-1β), and interleukin-6(IL-6) in adiponectin(APN), insulin, and inflammatory factor signaling pathways were detected by Western blot and real-time RCR, respectively. The results showed that 6-gingerol at a high dose could significantly decrease the fasting plasma content of NEFA and insulin and reduce Adipo-IR. Additionally, 6-gingerol at a high dose significantly increased the protein and mRNA expression of APN, AdipoR1, PGC-1α, and PI3 K in eWAT, elevated the relative expression of p-AMPK~(Thr172) and p-Akt~(Ser 473), reduced the protein and mRNA expression of TNF-α, IL-1, and IL-6 in eWAT, and decreased the relative expression of p-JNK1 and p-JNK2. This study reveals that 6-gingerol can improve insulin sensitivity of adipose tissues in aging rats with glycolipid metabolism disorders, and this effect is presumedly achieved by enhancing the PI3 K/Akt signaling pathway, inhibiting adipose tissue inflammation, increasing APN synthesis, enhancing AdipoR1 expression, and activating its downstream AMPK/PGC-1α signaling pathway.
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Animals , Male , Rats , Adipose Tissue , Aging , Catechols , Fatty Alcohols , Insulin Resistance , Rats, Sprague-DawleyABSTRACT
OBJECTIVE@#Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.@*METHODS@#An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins.@*RESULTS@#XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.@*CONCLUSION@#Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.
Subject(s)
Animals , Mice , AMP-Activated Protein Kinases/metabolism , Acetyl-CoA Carboxylase/metabolism , Adiponectin/metabolism , Antidepressive Agents/pharmacology , China , Depression/drug therapy , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Glucose , Hypothalamus/metabolism , Receptors, Adiponectin/metabolismABSTRACT
OBJECTIVE: 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. METHODS: 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. RESULTS: Following modeling, the average escape latency of Morris water maze tests was significantly prolonged (P0.05). CONCLUSION: 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.
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Objective To discuss effects of three different-intensity exercise on oxidative stress and adiponectin/adiponectin receptor1/2 of the liver in obese rats.Methods Thirty-two Sprague-Dawley rats were fed high-lipid fodder and became the obesity model after 16 weeks.Then they were randomly divided into a high-lipid control group (HF),a low-intensity exercise group (HS),a moderate-intensity exercise group (HM) and an exercise group with progressive intensity (HI),each of 8.Another 8 rats were chosen into a normal control group (NC).The speed of treadmill running of group HS and HM was 10m/min and 15m/min respectively,while that of group HI was10m/min for 20 min,followed by another 20min at and still another 20min at 28～30m/min,five days a week for 6 weeks.Six weeks later,the weight,alanine transaminase (ALT),aspartate transaminase (AST),superoxide dismutase (SOD),malondialdehyde (MDA),tumor necrosis factor alpha (TNF-α),interleukin-6 (IL-6),adiponectin receptors1/2,adiponectin,triglyceride (TG),cholesterol (TC),high-density lipoproteincholesterol (HDL-C),low-density lipoproteincholesterol (LDL-C) and free fatty acid (FFA) were tested.Results Compared with group NC,significant increase was observed in the average weight,TG,TC,LDL-C,FFA,ALT,AST,MDA,TNF-α and IL-6 (P＜0.05 or P＜0.01),while significant decrease was found in the average HDL-C,SOD,adiponectin and adiponectin receptors1/2 of group HF (P＜0.05 or P＜0.01).Compared with group HF,there was significant decrease in the average weight,TG,LDL-C,FFA,ALT,MDA,TNF-α and IL-6 (P＜0.05 or P＜0.01),but significant increase in the average SOD,adiponectin,AR1 and AR2 of group HS,HM and HI (P＜0.05 or P＜0.01),and only HDL-C of group HM increased significantly(P＜0.05).Compared with group HS and HI,significant decrease was found in the average FFA and MDA (P＜0.05),while significant increase was found in the average adiponectin and AR2 of group HM (P＜0.05).Conclusion Aerobic exercise can improve abnormal hepatic lipid metabolism and oxidative stress,strengthen free radical scavenging capacity,prevent liver cell inflammation injury and ameliorate liver metabolism disorder of obese rats induced by high-lipid fodder.Moreover,the effect of moderate-intensity exercise is superior to low-intensity exercise or exercise with progressive intensity,whose mechanism may be related to further activating liver adiponectin receptor 2 through increasing serum adiponectin.
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AIM:To investigate the protective effect of curcumin analogue L 6H4 on diaphragm of type 2 dia-betic rats.METHODS: SPF male Sprague-Dawley rats ( n=40) were randomly divided into 5 groups: normal control (NC) group, high fat (HF) group, high fat+L6H4 treatment (FT) group, diabetes mellitus (DM) group and DM +L6H4 treatment (DT) group.The rats in the later 4 groups were fed with high-fat diet.After 4 weeks of high-fat diet fee-ding, the rats in DM and DT groups were intraperitoneally injected with streptozotocin to induce type 2 diabetes melliutus. The rats in FT and DT groups were given L6H4 by gavage for 8 weeks.Blood glucose and blood lipid levels were detected biochemically .Fasting serum insulin ( FINS ) level was measured by radioimmunoassay and insulin resistance index (HOMA-IR) was calculated.Serum adiponectin (APN) level was measured by ELISA.The morphological changes of the diaphragm were observed under light and transmission electron microscopes .Lipid deposition and the activity of succinate dehydrogenase (SDH) and NADH-tetrazolium reductase (NADH-TR) were observed by enzyme histochemical staining . The content of malondialdehyde ( MDA) and the activity of superoxide dismutase ( SOD) in the diaphragm were measured by thiobarbituric acid method and hydroxylamine method , respectively .The protein expression of adiponectin receptor 1 ( AdipoR1) in the diaphragm was determined by immunohistochemistry and Western blot .RESULTS:The levels of blood lipids , blood glucose , FINS and HOMA-IR in HF and DM groups were higher than those in NC group , but decreased after L6H4 treatment.The serum APN level in HF and DM groups was lower than that in NC group , but increased after treat-ment with L6H4.The muscle fibers of the diaphragm were shrunk , fat particles accumulated in the muscle fibers , and the mitochondria were slightly swollen in HF and DM groups .The diaphragmatic fibrosis was obvious in DM group .These le-sions were relieved after L6H4 treatment.Compared with NC group, the level of MDA and the activity of SDH and NADH-TR in the diaphragm were increased in HF and DM groups , but decreased after treatment with L 6H4.The activity of SOD and the expression of AdipoR1 in the diaphragm were lower than those in NC group , but increased after L6H4 treatment. CONCLUSION: The curcumin analogue L6H4 exerts a protective effect on diaphragm in type 2 diabetic rats.The strengthened protein expression of AdipoR 1, the increased serum level of APN , and anti-lipid peroxidation may be involved in the process .
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Objective To explore the effects of telmisartan on expression of peroxisome proliferators PPARs activated receptors and adiponectin receptor 2 in rats with nonalcoholic steatohepatitis (NASH).Methods Forty male SD rats were randomized into normal-diet control group (NC,n=15),high fat-diet control group (FC,n=15),and high fat-diet with telmisartan group (FT,n =10).NC group was given standard diet and the other two groups were given high-fat diet.At the end of the 12th week,5 rats which were randomly selected from both the NC and FC groups were given euglycermic hyperinsulinemia clamp to see if fat-liver model of rats with insulin resistance was successfully induced,and rat livers were removed for pathological examination to determine the extents of NASH.Afterwards,rats in the FT group was given telmisartan (5 mg/kg·d) while rats in both the NC and FC groups were given the same volume of 0.9% saline solution by intragastric gavage for another 4 weeks.After glucose infusion rates (GIRs) were obtained by the euglycermic hyperinsulinemia clamp technique at the end of the 16th week,all rats were sacrificed and the body weight was recorded,and serum lipids,aminotransferases and fasting blood glucose were measured.The mRNA expressions of peroxisome proliferator activated receptors (PPARs),adiponectin receptor-2 and angiotensin II type-1 receptor in the liver tissue were assessed by semi-quantitative reverse transcriptase polymerase chain reactions.Results The expressions of PPARα,PPARγ and AdipoR2 mRNA in the liver tissue of FC group were decreased significantly compared with the NC group (P<0.01),and the expression of AT1R mRNA of the liver tissue in FC group was increased significantly compared with NC group (P<0.01).Compared with the FC group,the expressions of PPARα,PPARγ and AdipoR2 mRNA in the FT group were increased (P<0.01).Serum aminotransferases,lipids and fasting blood glucose level in the rats of FC group were increased significantly compared with rats of the NC group (P<0.01),and serum aminotransferases,lipids and fasting blood glucose level in the rats of FT group were greatly improved compared with the FC group.Conclusions Telmisartan can improve glucose and lipid metabolism,stop weight gain,decrease liver index,and alleviate steatosis and inflammation of NASH rats by improving insulin resistance.Telmisartan may play an effective role in the protection of rat liver with NASH.
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Objective:To evaluate the effects of rosiglitazone (ROS) on the expression of adiponectin receptors (AdipoR1 and AdipoR2) mRNA in gingival tissue and inflammatory factors,and on the potential of bone loss in the rats with experimental periodontitis.Methods:10 male Sprague-Dawley rats without treatment were used as the controls;40 were used for the creation of periodontis models and then treated by rosiglitazone at 0(periodontitis control),1,3,10 mg/kg(low,median and high dose groups) respectively 1/d for 4 weeks.RT-PCR was used to examine the expression of AdipoR1 and AdipoR2 mRNA in gingiva tissue.Levels of gingival TNF-α,MMP-9 and plasma adiponectin was measured by ELISA.CEJ-A was measured for the evaluation of alveolar bone loss by standard digital photographs.Results:The expression levels of gingival AdipoRl and AdipoR2 mRNA in periodontitis group is lower than that in the control group(P ＜ 0.01).The concentration of plasma adiponectin had no significant difference between control group and periodontitis group(P ＞ 0.05).The concentration of gingival TNF-α,MMP-9 in periodontitis group was significantly higher than that in control group (P ＜ 0.01).Compared with periodontitis group,ROS treatment increased the expression levels of AdipoR1 mRNA(P ＜ 0.05)and decreased the concentration of TNF-α in gingival tissue.Median and high dose treatment increased the expression levels of AdipoR2 (P ＜ 0.01) and the concentration of plasma adiponectin(P ＜ 0.05),decreased the concentration of MMP-9 in gingival tissue (P ＜ 0.01)and the alveolar bone loss(P ＜ 0.01).Conclusion:Rosiglitazone treatment may reduce inflammatory response and suppress the bone resorption probably through up-regulation of the expression of adiponectin receptors and decrease of the concentration of TNF-α,MMP-9 in gingival tissue.
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Objective To probe the new mechanism of simvastatin on high-fat diet-induced kidney dam-age. Methods Female SD rats were subjected to a standard control diet(SCD)or high-fat diet(HFD)for 20 weeks,then the HFD group was randomly divided into HFD group and HFD group with simvastatin treatment (HFD+ST,10mg·kg-1·d-1 )for another 8 weeks. The expression of adiponectin,adiponectin receptors R1 and R2, Adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK),peroxisome proliferator-activated receptorα(PPARα),glucose regulated protein 78(GRP78)and GADD153(CHOP)in kidney were assessed respective-ly. Results Body weight and serum lipid levels in HFD group significantly increased ,expression of adiponectin and its receptors significantly down-regulated. Phosphorylation of AMPKα and PPARα expression decreased,and expression of GRP78 and CHOP up-regulated significantly. Above indexes in simvastatin treatment groups improved significantly. Conclusion Simvastatin can improve high-fat induced kidney damages ,probably by increasing expression of adiponectin and its receptors ,decreasing endoplasmic reticulum stress.
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AIM:To investigate the protective effect of curcumin analogue L 6H4 on diaphragm of type 2 dia-betic rats.METHODS: SPF male Sprague-Dawley rats ( n=40) were randomly divided into 5 groups: normal control (NC) group, high fat (HF) group, high fat+L6H4 treatment (FT) group, diabetes mellitus (DM) group and DM +L6H4 treatment (DT) group.The rats in the later 4 groups were fed with high-fat diet.After 4 weeks of high-fat diet fee-ding, the rats in DM and DT groups were intraperitoneally injected with streptozotocin to induce type 2 diabetes melliutus. The rats in FT and DT groups were given L6H4 by gavage for 8 weeks.Blood glucose and blood lipid levels were detected biochemically .Fasting serum insulin ( FINS ) level was measured by radioimmunoassay and insulin resistance index (HOMA-IR) was calculated.Serum adiponectin (APN) level was measured by ELISA.The morphological changes of the diaphragm were observed under light and transmission electron microscopes .Lipid deposition and the activity of succinate dehydrogenase (SDH) and NADH-tetrazolium reductase (NADH-TR) were observed by enzyme histochemical staining . The content of malondialdehyde ( MDA) and the activity of superoxide dismutase ( SOD) in the diaphragm were measured by thiobarbituric acid method and hydroxylamine method , respectively .The protein expression of adiponectin receptor 1 ( AdipoR1) in the diaphragm was determined by immunohistochemistry and Western blot .RESULTS:The levels of blood lipids , blood glucose , FINS and HOMA-IR in HF and DM groups were higher than those in NC group , but decreased after L6H4 treatment.The serum APN level in HF and DM groups was lower than that in NC group , but increased after treat-ment with L6H4.The muscle fibers of the diaphragm were shrunk , fat particles accumulated in the muscle fibers , and the mitochondria were slightly swollen in HF and DM groups .The diaphragmatic fibrosis was obvious in DM group .These le-sions were relieved after L6H4 treatment.Compared with NC group, the level of MDA and the activity of SDH and NADH-TR in the diaphragm were increased in HF and DM groups , but decreased after treatment with L 6H4.The activity of SOD and the expression of AdipoR1 in the diaphragm were lower than those in NC group , but increased after L6H4 treatment. CONCLUSION: The curcumin analogue L6H4 exerts a protective effect on diaphragm in type 2 diabetic rats.The strengthened protein expression of AdipoR 1, the increased serum level of APN , and anti-lipid peroxidation may be involved in the process .
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Numerous epidemiological studies have studied the association of adiponectin (ADIPOQ) gene and adiponectin receptor (ADIPOR) gene polymorphisms with risk of colorectal cancer (CRC),but the outcomes were incomplete and inconsistent.Therefore,we conducted a meta-analysis to assess the associations systematically.All eligible case-control studies published up to Jan.2015 were searched from PubMed,the Cochrane library,Elsevier,Wiley Online library,China National Knowledge Infrastructure,WanFang data and Chongqing VIP.Effect sizes of odds ratio (OR) and 95％ confidence interval (95％CI) were calculated by using a fixed-or random-effect model.Twelve case-control studies including 6141 cases and 7398 controls were selected.Significant differences in the distributions of allele frequency with CRC risk were directly present in ADIPOQ variants rs2241766,rs1501299 and ADIPOR variant rs1342387.In stratified analysis for different populations,significant differences were present in ADIPOQ variant rs822396 for Ashkenazi Jewish,in ADIPOQ variant rs1501299 and ADIPOR variant rs1342387 for Chinese and in ADIPOQ variant rs 2241766 for Ashkenazi Jewish and Chinese.In addition,the factors correlated with insulin resistance had synergistic effect with ADIPOQ variants rs2241766 T/G and rs1501299 G/T on risk of CRC.ADIPOQ variants rs2241766 T/G,rs1501299 G/T and ADIPOR variant ADIPOR rs1342387 G/A had a population specific correlation with CRC risk,which may be mediated by insulin resistance.And large well-designed studies are still needed for further evaluation of rs822396 and rs1063538,especially for their interaction and combined effect in the correlation with CRC risk.
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Objective To explore the relationship between genetic polymorphisms of ADIPOR2 with serum APN level ,inti‐ma‐media thickness(IMT)and atherothrombosis cerebral infarction risk .Methods The case control study was adopted ,300 patients with atherothrombosis cerebral infarction in our hospital from September 2009 to September 2014 were selected as the observation group ,meanwhile contemporaneous 300 individuals undergoing the physical examination were selected as the control group .The clinical data in all the subjects were collected and performed the carotid arterial examination ,the serum APN level was detected ,the rs12342 polymorphism of ADIPOR2 gene was detected .The genetic polymorphisms of ADIPOR2 were compared between the two groups and its relationship with serum APN and IMT was analyzed .Results The probability for suffering from atherothrombosis cerebral infarction in the AA genotype was increased compared with the GG genotype ,the difference was statistically significant (OR=1 .903 ,95% CI:1 .092-2 .703 ,P=0 .011) .Compared with the control group ,the IM T values in various subgenotype groups of the observation group were elevated ,while the APN levels were decreased ,the differences were statistically significant ( P<0 .01) .Compared with the genotype GG ,the IM T values in the genotype AA and AG were increased and APN levels were de‐creased ,the differences were statistically significant (P<0 .01) .Conclusion Genetic polymorphisms of ADIPOR2 maybe a genetic locus for the pathogenesis of Chinese Han people of atherothrombosis cerebral infarction .
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Objective To investigate the role of adiponectin (ADP) and its receptors (ADR) in pati ents with primary gouty arthritis (GA).Methods Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of plasma ADP in 88 GA and 80 healthy controls (NC).Real time quantitative polymerase chain reaction (RT-qPCR) was employed to study the expression of ADR1 and ADR2 mRNA in peripheral blood mononuclear cells (PBMCs).The biochemical indicator of TG,HDL,LDL,VLDL,apoA1,apoB100 and uric acid (UA) were detected at the same time.T test,Spearman's correlations and regression analysis were used for statistical analysis.Results The concentration of plasma ADP was significantly lower in GA than that in NC [(6±7) μg/ml,(8±6) μg/ml,t=-3.71,P＜0.01 ],the expression of ADR1 and ADR2 mRNA in GA (ADR1:0.09±0.08,ADR2:0.0122±0.0164) was significantly increased when compared to the NC (ADR1:0.05±0.03,ADR2:0.0054±0.0024) (t=2.71,2.35,P＜0.05).In the GA patients,the level of ADP was negatively correlated with the lymphocytes count (LY) and UA (r=-0.32,-0.36,P＜0.05),and it was positively correlated with ESR and LDL level (r=0.31,0.39,P＜0.05).The expression of ADR1 mRNAwas negatively correlated with TG (r=-0.43,P＜0.05 ),but positivdy correlated with ESR and CRP level (r=0.45,0.57,P＜0.05).The expression of ADR2 mRNA was negatively correlated with glucose and UA(r=-0.50,-0.59,P＜0.05).Conclusion Altered expression of ADP and its receptors may be involved in thepathogenesis of gouty inflammation.
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Objective To study the effects and mechanisms of resveratrol (Resv) on the expression of adiponectin receptors ( AdipoR1 and AdipoR2 ) in rat mesangial cells (MCs) cultured in intermittent high glucose medium.Methods The MCs cultured in normal glucose ( 5.6 mmol/L) medium were transfected by the plasmid vector of the FoxO1 short hairpin RNAs ( FoxO1 shRNA ),and then cultured in intermittent high glucose medium (5.6mmol/L or 30 mmol/L,alternately every 8 hours ) and resveratrol ( Resv 20 μmol/L).The MCs cultured in normal glucose (5.6 mmol/L) medium served as normal glucose control group (NG),and the MCs exposed to iutermittent high glucose medium were divided into five groups:intermittent high glucose group (IHG),IHG+Resv group,IHG+FoxO1 shRNA group,IHG+ Resv + FoxO1 shRNA group,IHG + Negative control group ( shNC ),each group was cultured for 72 h.The level of reactive oxygen species (ROS) was assessed by Fluorescence microplate reader.The mRNA levels of Sirt1,Foxo1,AdipoR1,and AdipoR2 were assessed by RT-RCR.The protein levels of FoxO1,phosphorylation FoxO1 ( p-FoxO1 ),AdipoR1,and AdipoR2 were assessed by Western blotting.Results ( 1 )Compared with NG,intermittent high glucose significantly decreased the mRNA expression of Sirt1,but markedly increased the level of p-FoxO1.Furthermore,the mRNA and protein expression levels of AdipoR1 were obviously decreased while the level of ROS was enhanced in IHG ( all P＜0.05 ).(2) Compared with IHG,the mRNA and protein expression levels of FoxO1 and AdipoR1 were inhibited,but the level of ROS was enhanced in group IHG+FoxO1 shRNA ( all P＜0.05 ).( 3 ) Compared with IHG,after treating with Resv,the mRNA expression level of Sirtl was increased,whereas the level of p-FoxO1 was decreased.Moreover,the mRNA and protein levels of AdipoR1 was increased while the level of ROS was lowered in group IHG+Resv (all P＜0.05 ).(4) Compared with group IHG+Resv,the mRNA and protein levels of FoxO1 and AdipoR1 were inhibited,but the level of ROS was increased in group IHG+Resv+FoxO1 shRNA (all P＜O.05).(5) In addition,the mRNA and protein expression level of AdipoR2 showed no significant difference among these groups ( P＞0.05 ).Conclusion ( 1 ) Resveratrol significantly increases the expression of AdipoR1 in MCs induced by intermittent high glucose.( 2 ) FoxO1 plays an important role in regulating the expression of AdipoR1 by resveratrol.
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There is a strong support for a role played by adiponectin in the function of ovary and placenta.There is evidence of direct effects of adiponectin on the late stages of folliculogenesis,and additive interactions of adiponectin with insulin and gonadotropins in inducing periovulatory changes in ovarian follicles.Adiponectin has demonstrated a potential effect on ovarian function as well as a possible effect on the formation of placenta,via multiple mechanisms,providing new strategies for the etiology investigation,prevention and treatment of reproductive and related metabolic diseases.
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PURPOSE: Obesity is a risk factor for asthma and type II diabetes. Peroxisome proliferator-activated receptor (PPAR)-gamma has been suggested to regulate inflammatory responses in diabetes and asthma. We investigated whether PPAR-alpha, PPAR-gamma, adiponectin receptors (AdipoR1, AdipoR2), leptin, and tumor necrosis factor (TNF)-alpha are expressed in rat lung tissues and whether the expression differs between obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long Evans Tokushima Otsuka (LETO) rats. MATERIALS AND METHODS: Obese and lean rats were given with a high fat diet or a 30% restricted diet for 32 weeks, and their blood glucose levels and weights were monitored. After 32 weeks, mRNA levels of PPAR-alpha, PPAR-gamma, AdipoR1, AdipoR2, leptin, and TNF-alpha in lung tissues were measured using real time PCR. RESULTS: PPAR-alpha, PPAR-gamma, AdipoR1, AdipoR2, leptin, and TNF-alpha were expressed in both obese and lean rat lung tissues. Increased serum glucose levels on intraperitoneal glucose tolerance testing and a higher weight gain at 32 weeks were observed in OLETF control rats compared to OLETF diet restricted rats. PPAR-gamma expression was markedly elevated in obese control and diet restricted rats compared to lean rats, although PPAR-gamma expression in obese rats was not affected by diet restriction. Leptin was highly expressed in OLETF rats compared to LETO rats. TNF-alpha expression was enhanced in OLETF control rats compared LETO diet restricted rats, and decreased by diet restriction. PPAR-alpha, AdipoR1, and AdipoR2 expression were not significantly different between obese and lean rats. CONCLUSION: PPAR-gamma was highly expressed in the lung tissues of obese rats and may be a novel treatment target for regulating lung inflammation associated with obesity.
Subject(s)
Animals , Male , Rats , Body Weight , Glucose Tolerance Test , Leptin/genetics , Lung/metabolism , Obesity/genetics , PPAR gamma/genetics , RNA, Messenger/metabolism , Rats, Long-Evans , Receptors, Adiponectin/genetics , Tumor Necrosis Factor-alpha/geneticsABSTRACT
Objective: To investigate the correlation of serum adiponectin and hepatic adiponectin receptor (adipoR) expression with pathological changes of the liver in the rats with non-alcoholic fatty liver diseases (NAFLD). Methods: The NAFLD model was induced by an oral administration of high fat diet. The rats were sacrificed at 2, 4, 8, and 12 weeks. ELISA was used to measure the serum adiponectin and other biochemical parameters. The liver index was also examined. AdipoR mRNA expression in the liver were measured by RT-PCR. Liver slices were observed with Sudan III staining, H-E staining and Masson staining for pathological changes. Results: The serum adiponectin in the model group were gradually decreased during the 2nd, 4th 8th and 12th week, and were all significantly lower than those in the control group at corresponding time points (P<0.01). Serum adiponectin level was found negatively correlated with the liver index (r=-0.383, P=0.015) hepatic inflammation scale (r= 0.475, P=0.002), and hepatic fibrosis scale (r=-0.353, P=0.025). The hepatic adipoR1 mRNA expression in the model group was gradually increased (P<0.01 from the 4th week) and adipoR2 mRNA expression was gradually decreased compared with the control group (P<0.01 from the 2nd week). AdipoR2 mRNA expression was negative correlated with liver index(r=-0.431, P=0.006) and hepatic fibrosis scale (r=-0.353, P=0.025). Conclusion: The hepatic adipoR mRNA expression is abnormal in rats with NAFLD; the serum adiponectin level is decreased and negatively correlated with liver inflammation and fibrosis scale, indicating that the decreased serum adiponectin level, pathological hepatic adipoR expression, especially the decreased AdipoR2 expression in the liver may be related to the pathogenesis of NAFLD.
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Objective To investigate the protective effect and possible mechanism of adiponectin (ADPN) and its receptors in diabetic nephropathy (DN). Methods A total of 64 Sprague-Dawley female rats were equally divided into diabetes mellitus (DM) group with streptozotocin(STZ) 60 mg/kg injection, and normal control (NC) group with the same dose of citric acid buffer randomly. At the end of 2, 6, 10 and 12 weeks, weight, fast blood glucose, 24-hour urinary albumin excretion, serum creatinine and serum fast blood insulin were measured. The level of adiponectin in urine and serum was examined by ELISA. The pathological change of kidney tissue was studied by periodic acid-Schiff's staining (PAS) and the expression of adiponectin receptor 1 (adipoR1), adiponectin receptor 2 (adipoR2) was determined by immunohistochemistry.The NRK-52E cells were cultured with 5 mmol/L glucose (control group), 30 mmol/L glucose (high glucose group), 30 mmol/L glucose+different concentrations of adiponectin (1 mg/L, 5 mg/L, 10 mg/L, ADPN groups), respectively. The mRNA expression of monocyte chemoattractant protein 1 (MCP-1) was measured by RT-PCR after 12 h. Results (1)Both in urine and serum, the levels of ADPN in DM group were higher than that in NC group after 6 weeks (P＜0.01) and increased gradually during the whole experiment. (2)Compared with NC group, the expressions of AdipoR1 and AdipoR2 in kidney tissues were elevated gradually in DM group. There was a significant positive correlation of ADPN with AdipoR1 and AdipoR2 in DM group(r=0.666, P＜0.01;r= 0.684, P＜0.01). (3)The expression of MCP-1 increased in high glucose group, but decreased in 1 mg/L, 5 mg/L, 10 mg/L adiponectin group. Conclusions The level of ADPN in urine and serum is positively correlated with its receptors and elevates with the process of diabetic kidney disease. High level of serum adiponectin plays a protective role through the direct action of AdipoR and the alleviation of MCP-1 expression in renal tubules.
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Objective To investigate the expression and significance of adiponectin(Adip) and the it's receptor 1, 2( AdipoR1, AdipoR2) in the pathogenesis of alcoholic liver disease ( ALD). Methods Fifty male Wistar rats were acclimatized for 7 days and then 10 rats were randomly assigned to be control. Others were to develop the rats mod-el of ALD by intragastric alcohol of increasing concentration and volume gradually [30% ～ 60%, 5 ～9 g/(kg · d)] , 8, 8, 8 and 9 rats were sacrificed randomly at the end of 4th, 8th, 12th and 16th week, liver samples and liver homogenate (10% ) were collected respectively. The concentration of triglyceride (TG) in the liver homogenate and the level of adiponectin and tumor necrosis alpha (TNFα) in the serum were measured by bi-ochemical chromatometry and ELISA method respectively. The mRNA and protein expression of Adip, AdipoRl and AdipoR2 in the hepatic tissue were performed by reverse transcription polymerase (RT-PCR) and Western blot. Results The model of rats alchoholic liver disease was developed. With the progress of ALD,the level of TG and TNFα in serum increased and the contention of Adip decreased gradually. The expression of Adip and AdipoR2 mRNA and protein decreased and no significant change was found in the AdipoRl. There is a negative correlationbetween the expression of serum Adip and AdipoR2 in hepatic tissue and the level of serum TNF-α and TG in the liver homogenate. ( r =-0. 98 ～-0. 90, P < 0. 01 ). The expression level of Adip protein was positively correlated with the contents of Adip in the serum ( r = 0. 90, P < 0. 01 ). Conclusion There is a close correlation between the decreased expression of Adip and AdipoR2 and adipose degenaration and inflammation in hepatic tissue.