AIM: To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 o...AIM: To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 on the mRNA level. METHODS: Fat fed rats were used as a model for fatty liver disease and bile duct ligation in mice to investigate cirrhotic liver. Expression of AdipoR1 and AdipoR2 mRNA was determined by real time RT-PCR. AdipoR1 protein was analysed by immunoblot. Adiponectin was measured by ELISA. RESULTS: Systemic adiponectin is reduced in fatfed rats but is elevated in mice after bile duct ligation (BDL). Hepatic adiponectin protein is lower in steatotic liver but not in the liver of BE)L-mice when compared to controls. Adiponectin mRNA was not detected in human liver samples or primary human hepatocytes nor in rat liver but recombinant adiponectin is taken up by isolated hepatocytes in-vitro. AdipoR1 mRNA and AdipoR1 protein levels are similar in the liver tissue of control and fat fed animals whereas AdipoR2 mRNA is induced. AdipoR2 mRNA and AdipoR1 mRNA and protein is suppressed in the liver of BDL-mice. CONCLUSION: Our studies show reduced circulating adiponectin in a rat model of fatty liver disease whereas circulating adiponectin is elevated in a mouse model of cirrhosis and similar findings have been described in humans. Diminished hepatic expression of adiponectin receptors was only found in liver cirrhosis.展开更多
In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical role...In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical roles in the pathogenesis of diabetes and metabolic syndrome. Here, we analyzed the endocytosis of adiponectin and adiponectin receptor 1 (AdipoR1) and found that they are both internalized into transferrin-positive compartments that follow similar traffic routes. Blocking clathrin-mediated endocytosis by expressing Eps15 mutants or depleting K^+ trapped AdipoR1 at the plasma membrane, and K^+ depletion abolished adiponectin internalization, indicating that the endocytosis of AdipoR1 and adiponectin is clathrin-dependent. Depletion of K^+ and overexpression of Eps15 mutants enhance adiponectin- stimulated AMP-activated protein kinase phosphorylation, suggesting that the endocytosis of AdipoR1 might down-regulate adiponectin signaling. In addition, AdipoR1 colocalizes with the small GTPase Rab5, and a dominant negative Rab5 abrogates AdipoR1 endocytosis. These data indicate that AdipoR1 is internalized through a clathrin- and Rab5- dependent pathway and that endocytosis may play a role in the regulation of adiponectin signaling.展开更多
[ Objective] To clone and analyze the sequence of Adiponectin receptor 1 ( AdipoR1 ) and receptor 2 (AdipoR2) cDNA of Guangxi Bama mini-pig. [Method] The Adiponectin receptors cDNAs were amplified by RT-PCR using ...[ Objective] To clone and analyze the sequence of Adiponectin receptor 1 ( AdipoR1 ) and receptor 2 (AdipoR2) cDNA of Guangxi Bama mini-pig. [Method] The Adiponectin receptors cDNAs were amplified by RT-PCR using skeletal muscle total RNA as template and then ligated into pMD18-T vector after purification. The recombinant pMD18-T vector was transformed into the E. coil DH5α for identification and sequencing. And the results were compared with the cDNA sequence from other species. [Result] The fragments, 1 128 bp and 1 161 bp in size, were amplified by RT-PCR and respectively consistent with the coding sequence of AdipoR1 gene and AdipoR2 gene. The homology analysis showed that the sequences of AdipoR1 gene and AdipoR2 gene were respectively 99.8% and 99.7% homologous to the sequence of domestic pig reported in GenBank with one base and three base missense mutations correspondingly. [ Conclusion] The AdipoR1 gene and AdipoR2. gene were successfully amplified from Guangxi Bama mini-pig, laying the foundation for the further study of the biological function of AdipoR genes and the design of novel drugs with AdipoR as target.展开更多
Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recog- nized for its therapeutic eff...Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recog- nized for its therapeutic effects on depressive disorders, although knowledge of the underlying mechanisms remains limited. Suppressed hippocampal neurogenesis in adult brains has been regarded, at least partly, contributive to depression, whereas physical exercise that restores neuro- genesis accordingly exerts the anti-depressive action. Several recent publications have suggested the potential role of adiponectin, a protein hormone secreted by peripheral mature adipocytes, in mediating physical exercise-triggered enhancement of hippocampal neurogenesis and alleviation of depression. Here, we briefly review these novel findings and discuss the possibility of counter- acting depression by modulating adiponectin signaling in the hippocampus with interventions including physical exercise and administration of pharmacological agents.展开更多
Background The genes encoding adiponectin receptor 1 (ADIPOR1) and small ubiquitin-like modifier 4 (SUM04) have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two g...Background The genes encoding adiponectin receptor 1 (ADIPOR1) and small ubiquitin-like modifier 4 (SUM04) have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two genes, acting separately or interacting, affect risk of coronary artery disease (CAD) without diabetes. Methods We genotyped 200 CAD patients without diabetes and 200 controls without CAD or diabetes at three single-nucleotide polymorphisms (SNPs) in ADIPOR1 and one SNP in SUM04, which were chosen based on previous studies. Potential associations were also explored between these SNPs and clinical characteristics of CAD without diabetes. Results Risk alleles at three SNPs inADIPOR1 (rs7539542-G, rs7514221-C and rs3737884-G) and the G allele at SNP rs237025 in SUM04 significantly increased risk of CAD without diabetes, with ORs ranging from 1.79 to 4.44. Carriers of any of these four risk alleles showed similar adverse clinical characteristics. Compared with individuals with a CC or GC genotype, those with a GG genotype at rs3737884 were at significantly higher risk of CAD that affected the left anterior descending coronary artery (OR: 6.77, P = 0.009), the right coronary artery (OR: 4.81, P = 0.028) or a relatively large number of vessels (P = 0.04). Individuals carrying a risk allele at one or more of the three SNPs in ADIPOR1 as well as a risk allele at the SNP in SUM04 were at significantly higher risk of CAD without diabetes than individuals not carrying any risk alleles (OR: 5.82, 95% CI: 1.23-27.7, P= 0.013). Conelusions SNPs in ADIPORl and SUMO4 are associated with elevated risk of CAD without diabetes, and SNPs in the two genes may interact to jointly affect disease risk.展开更多
In order to confirm whether the mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were correlated with the serum parameters of glucose and lipid metabolism and to clarify ...In order to confirm whether the mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were correlated with the serum parameters of glucose and lipid metabolism and to clarify the regulation of adiponectin receptor gene expression in diabetic states, serum adiponectin, mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were examined in type 2 diabetic rats. The model of type 2 diabetes was prepared by feeding high fat diet and injecting low dosage of streptozotocin (STZ). The diabetic rats were screened out by oral glucose tolerance test. One group of type 2 diabetic rats received rosiglitazone. The serum adiponectin concentration was detected by using ELISA and mRNA levels were examined by RT-PCR. The serum adiponectin levels and mRNA levels of adiponectin in adipose tissue of type 2 diabetic rats were significantly decreased as compared with the normal control rats (P<0.05, P<0.01 respectively). No siglificant changes were observed in the expression of adiponectin receptor 1 in the skeletal muscle of type 2 diabetic rats. The mRNA levels of adiponectin in adipose tissue were reversely correlated with serum insulin (r=-0.66, P<0.05), triglyceride (r=-0.58, P<0.05), cholesterol (r=-0.49, P<0.05), interleukin-6 (r=-0.49, P<0.05) and tumor necrosis factor (r=-0.43, P<0.05). The expression of adiponectin receptors was not altered in the skeletal muscle of Type 2 diabetic rats. The decreased serum adiponectin was caused by the decreased expression of adiponectin mRNA in adipose tissue rather than the adiponectin receptors in the skeletal muscle, which could be improved by rosiglitazone.展开更多
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 ...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 Pub Med,the Cochrane library,Elsevier,Wiley Online library,China National Knowledge Infrastructure,Wan Fang 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.展开更多
Background:Epidemiologic and genetic studies suggest a link between insulin resistance (IR) and endometrial cancer,and endometrial hyperplasia (EH) is a precancerous stage of endometrial cancer.Adiponectin is an ...Background:Epidemiologic and genetic studies suggest a link between insulin resistance (IR) and endometrial cancer,and endometrial hyperplasia (EH) is a precancerous stage of endometrial cancer.Adiponectin is an adipokine which previously shown to be a risk factor for endometrial cancer.The aim of the study was to develop a rat model of IR and EH and evaluate adiponectin system in circulation and uterus.Methods:This study was a 46-week animal trial from February 2014 to January 2015.Female Sprague-Dawley rats were fed with high-fat diet (HFD) for 40 weeks to induce IR.Followed by ovariectomization,rats were orally administrated to 173-estradiol (E2) for 4 weeks to induce EH and then sacrificed.A total of 36 rats were divided into four groups:E2,HFD,HFD + E2,and control groups.Data were analyzed with Student's t-test,one-way analysis of variance (ANOVA),and Mann-Whitney U-tests.Chi-square was used to evaluate the score of immunohistochemistry.Results:The thickness ofendometrial,glandular epithelium,and myometrium in the HFD-E2 group were higher than the E2 group (F=59.02,F=23.51 and F =12.53,respectively,all P 〈 0.00 1).Plasma adiponectin levels in the E2 group were lower than those in the control group,and the levels in the HFD-E2 group were lower than those in the HFD group (F =13.15,P 〈 0.05).However,after normalized to visceral adipose tissue,compared to the control group,plasma adiponectin levels were decreased in rat with HFD in the absence or presence of E2,respectively (F =6.72,P 〈 0.05).Adiponectin gene (F =10.48,P 〈 0.05) and protein (P 〈 0.05) levels in uterus in the HFD-E2 group were higher than those in the HFD group.Conclusions:This study manifests that IR can effectively modulate EH,which suggests the involvement of energetic metabolism in uterine alternation.The combination effects of IR and EH modulate circulating adiponectin levels.However,adiponectin gene and protein levels in uterus are mainly response to estradiol.展开更多
Obesity-linked type 2 diabetes is one of the paramount causes of morbidity and mortality worldwide,posing a major threat on human health,productivity,and quality of life.Despite great progressmadetowards a better unde...Obesity-linked type 2 diabetes is one of the paramount causes of morbidity and mortality worldwide,posing a major threat on human health,productivity,and quality of life.Despite great progressmadetowards a better understanding of the molecular basis of diabetes,the available clinical counter-measures against insulin resistance,a defect that is central to obesity-linked type 2 diabetes,remain inadequate.Adiponectin,an abundant adipocyte-secreted factor with a wide-range of biological activities,improves insulin sensitivity in major insulin target tissues,modulates inflammatory responses,and plays a crucial role in the regulation of energy metabolism.However,adiponectin as a promising therapeutic approach has not been thoroughly explored in the context of pharmacological intervention,and extensive efforts are being devoted to gain mechanistic understanding of adiponectin signaling and its regulation,and reveal therapeutic targets.Here,we discuss tissue-and cell-specific functions of adiponectin,with an emphasis on the regulation of adiponectin signaling pathways,and the potential crosstalk between the adiponectin and other signaling pathways involved in metabolic regulation.Understanding better just why and how adiponectin and its downstream effector molecules work will be essential,together with empirical trials,to guide us to therapies that target the root cause(s)of type 2 diabetes and insulin resistance.展开更多
Background Endothelial dysfunction is a key event in the onset and progression of atherosclerosis in diabetic patients. Apoptosis may lead to endothelial dysfunction and contribute to vascular complications. However, ...Background Endothelial dysfunction is a key event in the onset and progression of atherosclerosis in diabetic patients. Apoptosis may lead to endothelial dysfunction and contribute to vascular complications. However, no study has addressed apoptosis in human umbilical vein endothelial cells (HUVECs) induced by an intermittent high-glucose media and its association with adiponectin receptor 1 (adipoR1), adipoR2, or adenosine monophosphate (AMP)-activated protein kinase (AMPK). Methods HUVECs were cultured in continuous normal glucose (5.5 mmol/L), continuous high glucose (25 mmol/L), alternating normal and high glucose and mannitol. In the alternating normal and high-glucose media, HUVECs were treated under different conditions. First, cells were transfected with the adipoRl-specific small-interfering RNA (siRNA) and then stimulated with globular adiponectin (gAD). Second, cells were cultured in both gAD and the AMPK activator 5-aminoimidazole-4-carboxamide-l-13-D-ribofuranoside (AICAR). Third, cells were cultured in the AMPK inhibitor adenine-9-13-D-arabino-furanoside (araA), gAD, and in AICAR. Results HUVEC apoptosis increased more significantly in an intermittent high-glucose medium than in a constant high-glucose medium. HUVEC apoptosis induced by an intermittent high-glucose medium was inhibited when the cells were pretreated with 3 pg/ml gAD, which rapidly activated AMPK and adipoR1 in HUVECs. However, adipoR2 was not activated. Conclusions We found that adipoR1, not adipoR2, is involved in mediating intermittent high-concentration glucose- evoked apoptosis in endothelial cells, gAD activated AMPK through adipoR1, leads to the partial inhibition of HUVEC apoptosis. A fluctuating glucose medium is more harmful than a constant high-glucose medium to endothelial cells.展开更多
Adiponectin,an adipokine synthesized by adipose tissue,has garnered significant attention in biomedical investigations.Research on its implications suggests that reduced adiponectin levels in the bloodstream might ser...Adiponectin,an adipokine synthesized by adipose tissue,has garnered significant attention in biomedical investigations.Research on its implications suggests that reduced adiponectin levels in the bloodstream might serve as a potential predisposing factor for several types of cancers,including gastric cancer.Although many studies on adiponectin levels in gastric cancer patients have been reported,its predictive role as a biomarker remains controversial.Moreover,the significance of adiponectin receptor expression as a prognostic factor in gastric cancer tissues varies across different research studies,and the precise mechanism by which adiponectin influences the initiation and advancement of gastric cancer remains to be fully elucidated.Furthermore,the anti-inflammatory and postoperative anti-infective effects of adiponectin are worth further investigation.Based on existing studies,it is commonly suggested that in the presence of low adiponectin levels,the stomach might be vulnerable to stimulation or damage from certain carcinogens,promoting gastric cancer development and progression.Considering its complex systemic effects and high serum concentration,adiponectin might serve as a homeostasis regulator and not necessarily as an anti-cancer factor.In this review,we explore the current research available on adiponectin in relation to gastric cancer and discuss its role and corresponding receptors involved in gastric cancer.展开更多
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.Xiaoy...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.展开更多
OBJECTIVE: To investigate the effects of the Traditional Chinese Medicine Qishan granules(TCM Qishan) on glucose and lipid metabolism, plasma adiponectin, and insulin resistance(IR) in a rat model of prediabetes.METHO...OBJECTIVE: To investigate the effects of the Traditional Chinese Medicine Qishan granules(TCM Qishan) on glucose and lipid metabolism, plasma adiponectin, and insulin resistance(IR) in a rat model of prediabetes.METHODS: A prediabetic rat model was established by high-fat diet-feeding. Sugar-free Qishan granules, rosiglitazone, or no treatment were then administered for 10 weeks, after which body mass,fasting blood glucose(FBG), 2-h postprandial blood glucose(2 hPG), hemoglobin A1c(HbA1c),fasting insulin(FINS), 2-h postprandial insulin(2hINS), plasma adiponectin(APN), plasma lipids,and free fatty acids(FFA), and liver pathology, were assessed.RESULTS: The mean mass of the rats treated with various doses of TCM Qishan was significantly lower(P < 0.01) than that of the prediabetic control rats, and that of the rats treated with a high dose of TCM Qishan was significantly lower(P < 0.01) than that of those treated with rosiglitazone. Metabolic indexes and IR were similarly improved by TCM Qishan and rosiglitazone treatment, with FBG, 2hPG,HbA1c, FINS, 2hINS, plasma triglyceride(TG), and FFA levels being significantly lower(P < 0.01), and APN concentration being significantly higher, in both of these treatment groups, than those of the prediabetic control group. The plasma total cholesterol and low-density lipoprotein-cholesterol concentrations of the treatment groups were also significantly lower(P < 0.05 and P < 0.01, respectively)than those of the prediabetic control group, but there were no significant differences in high-density lipoprotein-cholesterol concentrations. A high dose of TCM Qishan was slightly more effective than rosiglitazone at reducing TG concentration.The prediabetic control rats demonstrated severe hepatic steatosis, and the high dose of TCM Qishan significantly ameliorated this.CONCLUSION: TCM Qishan significantly reduces weight gain, ameliorates defects in glucose and lipid metabolism, and increases insulin sensitivity and plasma APN concentration in prediabetic rats. The effect of TCM Qishan on body mass was superior to that of rosiglitazone, and its other effects were of similar magnitude.展开更多
基金Supported by a grant from the Deutsche Forschungsgemeinschaft (BU 1141/3-2)
文摘AIM: To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 on the mRNA level. METHODS: Fat fed rats were used as a model for fatty liver disease and bile duct ligation in mice to investigate cirrhotic liver. Expression of AdipoR1 and AdipoR2 mRNA was determined by real time RT-PCR. AdipoR1 protein was analysed by immunoblot. Adiponectin was measured by ELISA. RESULTS: Systemic adiponectin is reduced in fatfed rats but is elevated in mice after bile duct ligation (BDL). Hepatic adiponectin protein is lower in steatotic liver but not in the liver of BE)L-mice when compared to controls. Adiponectin mRNA was not detected in human liver samples or primary human hepatocytes nor in rat liver but recombinant adiponectin is taken up by isolated hepatocytes in-vitro. AdipoR1 mRNA and AdipoR1 protein levels are similar in the liver tissue of control and fat fed animals whereas AdipoR2 mRNA is induced. AdipoR2 mRNA and AdipoR1 mRNA and protein is suppressed in the liver of BDL-mice. CONCLUSION: Our studies show reduced circulating adiponectin in a rat model of fatty liver disease whereas circulating adiponectin is elevated in a mouse model of cirrhosis and similar findings have been described in humans. Diminished hepatic expression of adiponectin receptors was only found in liver cirrhosis.
文摘In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical roles in the pathogenesis of diabetes and metabolic syndrome. Here, we analyzed the endocytosis of adiponectin and adiponectin receptor 1 (AdipoR1) and found that they are both internalized into transferrin-positive compartments that follow similar traffic routes. Blocking clathrin-mediated endocytosis by expressing Eps15 mutants or depleting K^+ trapped AdipoR1 at the plasma membrane, and K^+ depletion abolished adiponectin internalization, indicating that the endocytosis of AdipoR1 and adiponectin is clathrin-dependent. Depletion of K^+ and overexpression of Eps15 mutants enhance adiponectin- stimulated AMP-activated protein kinase phosphorylation, suggesting that the endocytosis of AdipoR1 might down-regulate adiponectin signaling. In addition, AdipoR1 colocalizes with the small GTPase Rab5, and a dominant negative Rab5 abrogates AdipoR1 endocytosis. These data indicate that AdipoR1 is internalized through a clathrin- and Rab5- dependent pathway and that endocytosis may play a role in the regulation of adiponectin signaling.
基金Supported by Guangxi Science Foundation (0542025)~~
文摘[ Objective] To clone and analyze the sequence of Adiponectin receptor 1 ( AdipoR1 ) and receptor 2 (AdipoR2) cDNA of Guangxi Bama mini-pig. [Method] The Adiponectin receptors cDNAs were amplified by RT-PCR using skeletal muscle total RNA as template and then ligated into pMD18-T vector after purification. The recombinant pMD18-T vector was transformed into the E. coil DH5α for identification and sequencing. And the results were compared with the cDNA sequence from other species. [Result] The fragments, 1 128 bp and 1 161 bp in size, were amplified by RT-PCR and respectively consistent with the coding sequence of AdipoR1 gene and AdipoR2 gene. The homology analysis showed that the sequences of AdipoR1 gene and AdipoR2 gene were respectively 99.8% and 99.7% homologous to the sequence of domestic pig reported in GenBank with one base and three base missense mutations correspondingly. [ Conclusion] The AdipoR1 gene and AdipoR2. gene were successfully amplified from Guangxi Bama mini-pig, laying the foundation for the further study of the biological function of AdipoR genes and the design of novel drugs with AdipoR as target.
基金supported by Hong Kong Health and Medical Research FundLeading Talents of Guangdong(2013)+3 种基金Programme of Introducing Talents of Discipline to Universities(B14036)Project of International,as well as Hong Kong,Macao&Taiwan Science and Technology Cooperation Innovation Platform in Universities in Guangdong Province,China(2013gjhz0002)grants to Jinan University Guangdong-Hong Kong-Macao Cooperation and Innovation Center for Tissue Regeneration and RepairState Key Laboratory of Pharmaceutical Biotechnology,Hong Kong SAR,China
文摘Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recog- nized for its therapeutic effects on depressive disorders, although knowledge of the underlying mechanisms remains limited. Suppressed hippocampal neurogenesis in adult brains has been regarded, at least partly, contributive to depression, whereas physical exercise that restores neuro- genesis accordingly exerts the anti-depressive action. Several recent publications have suggested the potential role of adiponectin, a protein hormone secreted by peripheral mature adipocytes, in mediating physical exercise-triggered enhancement of hippocampal neurogenesis and alleviation of depression. Here, we briefly review these novel findings and discuss the possibility of counter- acting depression by modulating adiponectin signaling in the hippocampus with interventions including physical exercise and administration of pharmacological agents.
基金Acknowledgments This study was funded by the National Natural Science Foundation of China (81570323, 30972709, 81061120527, 81241082) and the 12th Five-Year National Program of the Ministry of Scientific Technology (2012BAI10B01). We thank Liu M and Zhou L from Beijing Hospital for providing experimental data, the nurses from Beijing Anzhen Hospital for collecting specimens, and the study volunteers.
文摘Background The genes encoding adiponectin receptor 1 (ADIPOR1) and small ubiquitin-like modifier 4 (SUM04) have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two genes, acting separately or interacting, affect risk of coronary artery disease (CAD) without diabetes. Methods We genotyped 200 CAD patients without diabetes and 200 controls without CAD or diabetes at three single-nucleotide polymorphisms (SNPs) in ADIPOR1 and one SNP in SUM04, which were chosen based on previous studies. Potential associations were also explored between these SNPs and clinical characteristics of CAD without diabetes. Results Risk alleles at three SNPs inADIPOR1 (rs7539542-G, rs7514221-C and rs3737884-G) and the G allele at SNP rs237025 in SUM04 significantly increased risk of CAD without diabetes, with ORs ranging from 1.79 to 4.44. Carriers of any of these four risk alleles showed similar adverse clinical characteristics. Compared with individuals with a CC or GC genotype, those with a GG genotype at rs3737884 were at significantly higher risk of CAD that affected the left anterior descending coronary artery (OR: 6.77, P = 0.009), the right coronary artery (OR: 4.81, P = 0.028) or a relatively large number of vessels (P = 0.04). Individuals carrying a risk allele at one or more of the three SNPs in ADIPOR1 as well as a risk allele at the SNP in SUM04 were at significantly higher risk of CAD without diabetes than individuals not carrying any risk alleles (OR: 5.82, 95% CI: 1.23-27.7, P= 0.013). Conelusions SNPs in ADIPORl and SUMO4 are associated with elevated risk of CAD without diabetes, and SNPs in the two genes may interact to jointly affect disease risk.
文摘In order to confirm whether the mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were correlated with the serum parameters of glucose and lipid metabolism and to clarify the regulation of adiponectin receptor gene expression in diabetic states, serum adiponectin, mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were examined in type 2 diabetic rats. The model of type 2 diabetes was prepared by feeding high fat diet and injecting low dosage of streptozotocin (STZ). The diabetic rats were screened out by oral glucose tolerance test. One group of type 2 diabetic rats received rosiglitazone. The serum adiponectin concentration was detected by using ELISA and mRNA levels were examined by RT-PCR. The serum adiponectin levels and mRNA levels of adiponectin in adipose tissue of type 2 diabetic rats were significantly decreased as compared with the normal control rats (P<0.05, P<0.01 respectively). No siglificant changes were observed in the expression of adiponectin receptor 1 in the skeletal muscle of type 2 diabetic rats. The mRNA levels of adiponectin in adipose tissue were reversely correlated with serum insulin (r=-0.66, P<0.05), triglyceride (r=-0.58, P<0.05), cholesterol (r=-0.49, P<0.05), interleukin-6 (r=-0.49, P<0.05) and tumor necrosis factor (r=-0.43, P<0.05). The expression of adiponectin receptors was not altered in the skeletal muscle of Type 2 diabetic rats. The decreased serum adiponectin was caused by the decreased expression of adiponectin mRNA in adipose tissue rather than the adiponectin receptors in the skeletal muscle, which could be improved by rosiglitazone.
基金supported by National Natural Science Foundation of China(No.81301691)the first Young Talents Foundation of Hubei Province(No.2014)+2 种基金Hubei Province Health and Family Planning Scientific Research Project(No.WJ2017Q023 and No.WJ2017M113)the Fundamental Research Funds for the Central Universities(No.2015LC029)Natural Science Foundation of Hubei Province(No.2016CFB356)
文摘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 Pub Med,the Cochrane library,Elsevier,Wiley Online library,China National Knowledge Infrastructure,Wan Fang 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.
基金This work was supported by a grant from the National Natural Science Foundation of China (No. 81272870).
文摘Background:Epidemiologic and genetic studies suggest a link between insulin resistance (IR) and endometrial cancer,and endometrial hyperplasia (EH) is a precancerous stage of endometrial cancer.Adiponectin is an adipokine which previously shown to be a risk factor for endometrial cancer.The aim of the study was to develop a rat model of IR and EH and evaluate adiponectin system in circulation and uterus.Methods:This study was a 46-week animal trial from February 2014 to January 2015.Female Sprague-Dawley rats were fed with high-fat diet (HFD) for 40 weeks to induce IR.Followed by ovariectomization,rats were orally administrated to 173-estradiol (E2) for 4 weeks to induce EH and then sacrificed.A total of 36 rats were divided into four groups:E2,HFD,HFD + E2,and control groups.Data were analyzed with Student's t-test,one-way analysis of variance (ANOVA),and Mann-Whitney U-tests.Chi-square was used to evaluate the score of immunohistochemistry.Results:The thickness ofendometrial,glandular epithelium,and myometrium in the HFD-E2 group were higher than the E2 group (F=59.02,F=23.51 and F =12.53,respectively,all P 〈 0.00 1).Plasma adiponectin levels in the E2 group were lower than those in the control group,and the levels in the HFD-E2 group were lower than those in the HFD group (F =13.15,P 〈 0.05).However,after normalized to visceral adipose tissue,compared to the control group,plasma adiponectin levels were decreased in rat with HFD in the absence or presence of E2,respectively (F =6.72,P 〈 0.05).Adiponectin gene (F =10.48,P 〈 0.05) and protein (P 〈 0.05) levels in uterus in the HFD-E2 group were higher than those in the HFD group.Conclusions:This study manifests that IR can effectively modulate EH,which suggests the involvement of energetic metabolism in uterine alternation.The combination effects of IR and EH modulate circulating adiponectin levels.However,adiponectin gene and protein levels in uterus are mainly response to estradiol.
基金supported by grants from the National Institutes of Health (R01 DK102965)the American Diabetes Association (#7-13-BS-043)to L.Q.D.
文摘Obesity-linked type 2 diabetes is one of the paramount causes of morbidity and mortality worldwide,posing a major threat on human health,productivity,and quality of life.Despite great progressmadetowards a better understanding of the molecular basis of diabetes,the available clinical counter-measures against insulin resistance,a defect that is central to obesity-linked type 2 diabetes,remain inadequate.Adiponectin,an abundant adipocyte-secreted factor with a wide-range of biological activities,improves insulin sensitivity in major insulin target tissues,modulates inflammatory responses,and plays a crucial role in the regulation of energy metabolism.However,adiponectin as a promising therapeutic approach has not been thoroughly explored in the context of pharmacological intervention,and extensive efforts are being devoted to gain mechanistic understanding of adiponectin signaling and its regulation,and reveal therapeutic targets.Here,we discuss tissue-and cell-specific functions of adiponectin,with an emphasis on the regulation of adiponectin signaling pathways,and the potential crosstalk between the adiponectin and other signaling pathways involved in metabolic regulation.Understanding better just why and how adiponectin and its downstream effector molecules work will be essential,together with empirical trials,to guide us to therapies that target the root cause(s)of type 2 diabetes and insulin resistance.
文摘Background Endothelial dysfunction is a key event in the onset and progression of atherosclerosis in diabetic patients. Apoptosis may lead to endothelial dysfunction and contribute to vascular complications. However, no study has addressed apoptosis in human umbilical vein endothelial cells (HUVECs) induced by an intermittent high-glucose media and its association with adiponectin receptor 1 (adipoR1), adipoR2, or adenosine monophosphate (AMP)-activated protein kinase (AMPK). Methods HUVECs were cultured in continuous normal glucose (5.5 mmol/L), continuous high glucose (25 mmol/L), alternating normal and high glucose and mannitol. In the alternating normal and high-glucose media, HUVECs were treated under different conditions. First, cells were transfected with the adipoRl-specific small-interfering RNA (siRNA) and then stimulated with globular adiponectin (gAD). Second, cells were cultured in both gAD and the AMPK activator 5-aminoimidazole-4-carboxamide-l-13-D-ribofuranoside (AICAR). Third, cells were cultured in the AMPK inhibitor adenine-9-13-D-arabino-furanoside (araA), gAD, and in AICAR. Results HUVEC apoptosis increased more significantly in an intermittent high-glucose medium than in a constant high-glucose medium. HUVEC apoptosis induced by an intermittent high-glucose medium was inhibited when the cells were pretreated with 3 pg/ml gAD, which rapidly activated AMPK and adipoR1 in HUVECs. However, adipoR2 was not activated. Conclusions We found that adipoR1, not adipoR2, is involved in mediating intermittent high-concentration glucose- evoked apoptosis in endothelial cells, gAD activated AMPK through adipoR1, leads to the partial inhibition of HUVEC apoptosis. A fluctuating glucose medium is more harmful than a constant high-glucose medium to endothelial cells.
文摘Adiponectin,an adipokine synthesized by adipose tissue,has garnered significant attention in biomedical investigations.Research on its implications suggests that reduced adiponectin levels in the bloodstream might serve as a potential predisposing factor for several types of cancers,including gastric cancer.Although many studies on adiponectin levels in gastric cancer patients have been reported,its predictive role as a biomarker remains controversial.Moreover,the significance of adiponectin receptor expression as a prognostic factor in gastric cancer tissues varies across different research studies,and the precise mechanism by which adiponectin influences the initiation and advancement of gastric cancer remains to be fully elucidated.Furthermore,the anti-inflammatory and postoperative anti-infective effects of adiponectin are worth further investigation.Based on existing studies,it is commonly suggested that in the presence of low adiponectin levels,the stomach might be vulnerable to stimulation or damage from certain carcinogens,promoting gastric cancer development and progression.Considering its complex systemic effects and high serum concentration,adiponectin might serve as a homeostasis regulator and not necessarily as an anti-cancer factor.In this review,we explore the current research available on adiponectin in relation to gastric cancer and discuss its role and corresponding receptors involved in gastric cancer.
基金This work was financially supported by the National Natural Science Foundation of China(No.81904091,No.81973748 and No,82174278)the National Natural Science Foundation of Guang-dong,China(No.2021A1515011212)+2 种基金Province Scientific Research Project of Traditional Chinese Medicine Bureau of Guangdong(No.20202039)Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University.Key.Area Research and Development Program of Guangdong Province(No.20208111100001)Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine.China.
文摘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.
基金Supported by Scientific Research Fund Project of Zhejiang Provincial Administration of traditional Chinese Medicine:Effect and Mechanism of Qishan Formula granule on simple Obesity based on intestinal flora-inflammatory immune Pathway(No.2019ZA083)
文摘OBJECTIVE: To investigate the effects of the Traditional Chinese Medicine Qishan granules(TCM Qishan) on glucose and lipid metabolism, plasma adiponectin, and insulin resistance(IR) in a rat model of prediabetes.METHODS: A prediabetic rat model was established by high-fat diet-feeding. Sugar-free Qishan granules, rosiglitazone, or no treatment were then administered for 10 weeks, after which body mass,fasting blood glucose(FBG), 2-h postprandial blood glucose(2 hPG), hemoglobin A1c(HbA1c),fasting insulin(FINS), 2-h postprandial insulin(2hINS), plasma adiponectin(APN), plasma lipids,and free fatty acids(FFA), and liver pathology, were assessed.RESULTS: The mean mass of the rats treated with various doses of TCM Qishan was significantly lower(P < 0.01) than that of the prediabetic control rats, and that of the rats treated with a high dose of TCM Qishan was significantly lower(P < 0.01) than that of those treated with rosiglitazone. Metabolic indexes and IR were similarly improved by TCM Qishan and rosiglitazone treatment, with FBG, 2hPG,HbA1c, FINS, 2hINS, plasma triglyceride(TG), and FFA levels being significantly lower(P < 0.01), and APN concentration being significantly higher, in both of these treatment groups, than those of the prediabetic control group. The plasma total cholesterol and low-density lipoprotein-cholesterol concentrations of the treatment groups were also significantly lower(P < 0.05 and P < 0.01, respectively)than those of the prediabetic control group, but there were no significant differences in high-density lipoprotein-cholesterol concentrations. A high dose of TCM Qishan was slightly more effective than rosiglitazone at reducing TG concentration.The prediabetic control rats demonstrated severe hepatic steatosis, and the high dose of TCM Qishan significantly ameliorated this.CONCLUSION: TCM Qishan significantly reduces weight gain, ameliorates defects in glucose and lipid metabolism, and increases insulin sensitivity and plasma APN concentration in prediabetic rats. The effect of TCM Qishan on body mass was superior to that of rosiglitazone, and its other effects were of similar magnitude.