New advances of adiponectin in regulating obesity and related metabolic syndromes

Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue vascularity.Based on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain cancers.Therefore,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors.The modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic strategies.In order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.

Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

Adiponectin orchestrates testosterone suppression in biological pathways

This current review highlights adiponectin engagement with AdipoR1 and AdipoR2 which subsequently triggers pathways such as AMPK,PPARα,and MAPK,thereby modulating testicular steroidogenesis.Adiponectin's actions on Leydig and adrenal cells inhibit androgen secretion by suppressing the steroidogenic acute regulatory protein(StAR).Given that StAR facilitates cholesterol to testosterone conversion,AMPK inhibits this process by modulating cholesterol transport and suppressing StAR expression through multiple avenues.Furthermore,adiponectin-induced PPARαactivation impedes mitochondrial cholesterol influx,further modulating androgen biosynthesis.The suppressive influence of PPARαon steroidogenic genes,notably StAR,is evident.Collectively,adiponectin signalling predominantly attenuates androgen production,ensuring metabolic and reproductive equilibrium.Imbalances,as seen in conditions like hypogonadism and obesity-related infertility,highlight their crucial roles and potential clinical interventions for reproductive disorders.

Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion

BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass(DJB)surgery is not clear.AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model.METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model.All adipose tissue was weighed and observed under microscope.Use inguinal fat to represent subcutaneous adipose tissue(SAT)and mesangial fat to represent visceral adipose tissue.RNA-sequencing was utilized to evaluate gene expression alterations adipocytes.The hematoxylin and eosin staining,reverse transcription-quantitative polymerase chain reaction,western blot,and enzyme-linked immunosorbent assay were used to study the changes.Insulin resistance was evaluated by immunofluorescence.RESULTS After DJB,whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved.Fat cell volume in both visceral adipose tissue(VAT)and SAT increased.Compared to SAT,VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone(GH)pathway and downstream adiponectin secretion were involved in metabolic regulation.The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased.Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity.CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB,possibly by increasing adiponectin secretion.

Study on the Correlation between Adiponectin and Bone Mineral Density in Postmenopausal Women from Guangxi Zhuang Autonomous Region

Objectives: To explore the relationship between adiponectin (APN) and bone mineral density in this Zhuang ethnic group, thus providing a basis underpinning the prevention and treatment of osteoporosis (OP). Methods: Zhuang women over 50 years old in Guangxi Zhuang Autonomous Region were included in the study. The broadband ultrasound attenuation (BUA) was adopted as the reference to calculate the T value. Quantitative ultrasonic bone density was measured on the right. Body composition measuring instrument was used to measure weight, fat, and muscle mass. Plasma APN level was detected by ELISA and blood lipids were detected by enzymatic method. Results: Plasma APN level was found with significant differences in the normal bone mineral density group, bone mineral density reduction group, and osteoporosis group (P β = −0.176, P = 0.001) when the partial correlation coefficient of APN is −0.210. Elevated APN was an independent risk factor for bone mineral density reduction (OR = 1.191, 95%CI: 1.004 - 1.407, P = 0.04) and OP (OR = 1.1337, 95%CI: 1.137 - 1.572, P Conclusion: Increased APN in postmenopausal women of Zhuang is an independent risk factor for OP. The application of APN in the OP screening and prevention of middle-aged and ageing Zhuang women still needs further research.

Adiponectin as a therapeutic target for diabetic foot ulcer

The global burden of diabetic foot ulcers(DFUs)is a significant public health concern,affecting millions of people worldwide.These wounds cause considerable suffering and have a high economic cost.Therefore,there is a need for effective strategies to prevent and treat DFUs.One promising therapeutic approach is the use of adiponectin,a hormone primarily produced and secreted by adipose tissue.Adiponectin has demonstrated anti-inflammatory and antiatherogenic properties,and researchers have suggested its potential therapeutic applications in the treatment of DFUs.Studies have indicated that adiponectin can inhibit the production of pro-inflammatory cytokines,increase the production of vascular endothelial growth factor,a key mediator of angiogenesis,and inhibit the activation of the intrinsic apoptotic pathway.Additionally,adiponectin has been found to possess antioxidant properties and impact glucose metabolism,the immune system,extracellular matrix remodeling,and nerve function.The objective of this review is to summarize the current state of research on the potential role of adiponectin in the treatment of DFUs and to identify areas where further research is needed in order to fully understand the effects of adiponectin on DFUs and to establish its safety and efficacy as a treatment for DFUs in the clinical setting.This will provide a deeper understanding of the underlying mechanisms of DFUs that can aid in the development of new and more effective treatment strategies.

Boiogito Increases the Synthesis and Secretion of Adiponectin by Promoting Differentiation in Cultured Human Adipocytes

Boiogito (BOT) ameliorates insulin resistance and diabetes in several animal models;however, the underlying mechanisms for these in vivo effects remain unclear. Thiazolidine derivatives, which are peroxisome proliferator-activated receptor γ (PPARγ) agonists for the treatment of type II diabetes, promote adiponectin production by inducing adipocyte differentiation, thereby reducing insulin resistance. This study aimed to evaluate the effect of BOT on adipocyte differentiation using cultured human visceral preadipocytes (HVPAds) compared with the thiazolidine derivative troglitazone (TRG). We investigated the effects of BOT (0.125 - 1 mg/mL) and TRG (10 μM) on the differentiation of adipocytes treated with or without tumor necrosis factor-α (TNF-α: 5 ng/mL). On day 14 of culture, the following adipocyte differentiation marker levels were measured: intracellular lipids, extracellular (i.e., medium) adiponectin, and intracellular differentiation-related genes (PPARγ, CCAAT/enhancer binding protein, adiponectin, differentiation cluster 36, glucose transporter type 4). BOT and TRG increased factors associated with differentiation including lipid, adiponectin, and differentiation-related gene expression levels compared with the controls. The increases in these differentiation markers were inhibited by the PPARγ antagonist GW9662 (20 μM). Furthermore, TNF-α decreased all differentiation marker levels. The decreases in differentiation markers were inhibited by BOT and TRG;however, these inhibitory effects were blocked by GW9662. The results suggest that BOT increases the synthesis and secretion of adiponectin by promoting differentiation similar to TRG. This study is the first to demonstrate that adipocyte differentiation-promoting activity is a mechanism for the beneficial effects of BOT on diabetes and insulin resistance.

Adiponectin and its receptors in rodent models of fatty liver disease and liver cirrhosis

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.

Adiponectin基因剔除LacZ基因敲入小鼠模型的建立

adiponectin是脂肪细胞特异分泌的一种活性蛋白质,具有增加胰岛素敏感性、抗炎及抗动脉硬化等活性.建立adiponectin基因剔除β-半乳糖苷酶基因(LacZ)敲入小鼠模型,可为整体动物水平研究adiponectin基因功能及其表达调控机制等提供理想工具.根据生物信息学方法获得adiponectin基因组序列,设计基因剔除及敲入策略,在adiponectin基因第2和第3号外显子剔除的同时,在其ATG和信号肽序列后顺接LacZ基因完整编码序列,构建完成了Adipo-LacZ-XpPNT基因剔除质粒.通过电穿孔将打靶质粒转入ES细胞,以G418和ganciclovir进行药物筛选,获得药物抗性的ES细胞克隆,PCR和DNA印迹鉴定出正确同源重组克隆.将同源重组的ES细胞克隆注入小鼠囊胚得到嵌合体小鼠,嵌合体小鼠与C57BL/6J小鼠交配产生杂合子小鼠,杂合子间交配获得adiponectin基因剔除LacZ基因敲入纯合子小鼠.经RT-PCR、RNA印迹和ELISA检测证实纯合子小鼠脂肪和血清中adiponectin基因表达呈阴性.RT-PCR、RNA印迹及蛋白质印迹检测发现,LacZ基因在突变小鼠脂肪组织中有特异性表达,其表达谱与内源性adiponectin基因的表达谱一致.但在脂肪组织及外周血中未能检测到LacZ活性,且血清中LacZ蛋白亦呈阴性.由此成功建立了adiponectin基因完全灭活及LacZ基因以内源性adiponectin基因表达谱表达的小鼠模型,为进一步研究该基因功能及其表达调控创造了有利条件.

脂源性分泌因子leptin、resistin、adiponectin、visfatin mRNA在子痫前期患者胎盘组织中表达及意义

目的:探讨子痫前期患者胎盘组织中脂源性分泌因子瘦素(leptin)、抵抗素(resistin)、脂联素(adiponectin)、内脂素(visfatin)mRNA表达水平及其意义。方法:采用RT-PCR方法测定36例正常足月妊娠妇女(A组)、24例轻度子痫前期患者(B组)和17例重度子痫前期患者(C组)胎盘组织中脂源性分泌因子leptin、resistin、adiponectin、visfatin mRNA表达水平。结果:①C组leptin、resistin mRNA表达水平分别为1.361±0.261、1.515±0.177,显著高于B组的0.898±0.201、1.055±0.113和A组的0.559±0.175、0.508±0.119(P<0.05);②C组adiponectin mRNA表达水平为0.222±0.115,显著低于B组的0.776±0.176和A组的1.422±0.193(P<0.05);③C组visfatin基因mRNA表达水平为0.253±0.119,显著低于B组的1.298±0.193和A组的1.308±0.208(P<0.05),B组与A组比较无显著差异(P>0.05)。结论:脂源性分泌因子leptin、resistin、adiponectin、visfatin在子痫前期的发病中有重要作用,可能参与了胰岛素抵抗的病理生理过程。

有氧运动联合KGM对高脂膳食大鼠胰岛素抵抗形成中肝脏Adiponectin/PPARα通路的影响

目的探讨胰岛素抵抗(IR)形成及其运动和KGM干预的机制。方法将6周龄50只雄性SD大鼠随机分为五组:对照组(C组)、高脂饮食组(HF组)、高脂饮食+运动组(HE组)、高脂饮食+葡甘聚糖组(HK组)、高脂饮食+运动训练+葡甘聚糖组(HEK级)。同时将HE、HK、HEK分别进行11 w无负重游泳训练。11 w后测定大鼠空腹血糖(FPG)、空腹胰岛素(FINS)、肝脏胆固醇(TC)、甘油三酯(TG)、脂联素(APN)、APN受体2(AdipoR2)、过氧化物增殖物激活受体α(PPARα)的蛋白含量。结果①HF组大鼠与C组相比,FPG、FINS含量以及胰岛素抵抗指数(HOMAIR)显著升高。②有氧运动和(或)KGM可以降低高脂膳食大鼠FPG水平、FINS以及HOMA-IR,并能显著降低肝脏中TG和TC含量。③与C组相比,HF组大鼠肝脏APN、PPARa含量显著降低,而HF组肝脏AdipoR2含量却升高,而通过双因素方差分析可知,有氧运动和(或)KGM可以显著增加肝脏APN含量和PPARα含量,降低肝脏AdipoR2含量。结论①11 w的高脂饮食可以诱导大鼠IR的形成,而高脂膳食引起的血脂代谢紊乱可能是引起IR产生的重要原因。②有氧运动或补充KGM可能通过改善高脂膳食大鼠肝脏Adiponectin/PPARα信号通路来调节血脂代谢,从而有效预防高脂膳食大鼠IR的形成。同时,有氧运动联合补充KGM对改善高脂大鼠肝脏Adiponectin/PPARα具有交互作用。

Adiponectin Gene Variation -4522C/T Is Associated with Type 2 Diabetic Obesity and Insulin Resistance in Chinese

The authors investigated the possible association of -4522C/T variation of adiponectin gene with coronary heart disease （CHD） and type 2 diabetes mellitus （T2DM）. Genotyping of SNP --4522C/T in 304 patients with CHD, 389 patients with T2DM, and 405 age and sex-matched healthy control subjects was carried out by means of PCR-RFLP approach. No significant difference in the genotype or allele frequencies was found, either between patients with CHD and control subjects, or between patients with T2DM and control subjects. However, in the subgroup analysis, an association of the TAr genotype and T allele with type 2 diabetes combined with obesity （BMI ≥ 25 kg/m2） was found （P = 0.014 and P = 0.034, respectively）. Also the homeostasis model assessment of insulin resistance （HOMA-IR） in T2DM patients with T/T genotype was significantly higher than that in T2DM patients carrying C allele （P = 0.0069）. The authors＇ findings for the first time demonstrated that SNP --4522 in the adiponectin gene was associated with T2DM that combined with obesity and higher insulin resistance index in patients with T2DM. This indicated that the variation might associate with an increased susceptibility to type 2 diabetic obesity and insulin resistance. But -4522C/T polymorphism did not contribute to the susceptibility of CHD.

脂连蛋白(adiponectin)对动脉粥样硬化小鼠的治疗作用及其机制

目的研究脂连蛋白(APN)对载脂蛋白E敲除(ApoE^(-/-))的动脉粥样硬化(AS)小鼠的治疗作用及可能机制。方法选取20只雄性ApoE^(-/-)小鼠通过高脂饮食建立AS模型,小鼠随机分为APN处理组及对照组。APN处理组给予腹腔注射重组小鼠APN(25μg/d),对照组给予腹腔注射等量生理盐水,共处理4周。采用HE染色和免疫组织化学染色、ELISA、免疫荧光标记技术、反转录PCR和Western blot分析其治疗作用和机制。结果与对照组相比,APN处理组动脉粥样硬化斑块面积、血管内白细胞介素8(IL-8)及肿瘤坏死因子α(TNF-α)水平均显著降低,血管周围脂肪组织炎症细胞浸润比例显著降低。APN处理组小鼠血管周围脂肪组织M1巨噬细胞标志物CD86及M1巨噬细胞下游促炎介质IL-1β表达均显著小于对照组,而M2巨噬细胞标志物CD206及M2巨噬细胞下游抗炎介质IL-10的水平均显著高于对照组。血管周围脂肪组织磷酸化的信号转导子与转录激活子6(p-STAT6)水平显著高于对照组。结论 APN对AS小鼠具有明确治疗效果,可能是通过激活STAT6信号诱导脂肪组织巨噬细胞M2巨噬细胞极化。

Study on Cloning and Polymorphism of Porcine Adiponectin Promoter

[ Objective] The aim of this study was to provide a basis for study on adiponectin as a candidate gene for fat deposition. [ Method] The promoter sequence of adiponectin was obtained by porcine BAC library screening and primer-walking method. The polymorphisms of adiponectin promoter from 290 pigs, including 5 breeds of Lantang pig, Large spotted pig, Large white pig, Landrace and Duroc, were analyzed with PCR-RFLP. [ Result] At SNP site of adiponectin 5＇-flanking region -1 010 bp （G/A）, GG genotype frequency in Chinese indigenous pigs was significantly higher than that in exotic pigs. At SNP site of adiponectin 5＇-flanking region -394 bp （T/C）, the genotype distribution of Chi- nese indigenous pigs was abundant, while no CC genotype was detected in exotic pigs, and T allele frequency was higher in exotic pigs. [ Conclusion] SNP site mutation of - 1 010 bp （G/A） may lead to changes of the gene transcription level, while SNP site of -394 bp （T/C） properly has no relationship with gene transcription level and fat deposition.

二甲双胍通过调节FGF21/adiponectin轴改善NAFLD大鼠脂代谢紊乱

目的探讨二甲双胍通过调节FGF21/adiponectin轴改善高脂诱导NAFLD大鼠脂代谢紊乱的作用。方法将25只SD大鼠予以高脂饮食喂养8周后,取5只证实NAFLD模型建立;继将剩余20只大鼠分为模型组(HF组)、二甲双胍干预组(HF+M组),每组10只,并继续给予高脂饮食;另取10只普通饮食饲养大鼠作为对照组(NC组)。于灌胃8周末,应用全自动生化分析仪检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆固醇(TC)、三酰甘油(TG)及空腹血糖(FBG);酶免法测定肝脏TG含量、血清胰岛素(FINS)、成纤维细胞生长因子(FGF21)及脂联素(Adiponectin)水平,并计算胰岛素抵抗指数(HOMA-IR);HE染色光镜下观察大鼠肝细胞脂肪变性情况;采用Real-time PCR法检测肝组织FGF21、AMPK mRNA表达及脂肪组织adiponectin mRNA表达。结果与NC组比较,HF组大鼠出现糖脂代谢紊乱及轻度肝功能受损,伴明显胰岛素抵抗、肝脏TG过度沉积及血清Adiponectin水平下降;二甲双胍干预后,可降低HF组大鼠血清TC、TG、FBG、ALT、AST、肝脏TG含量及HOMA-IR(P<0.05),升高血清adiponectin及FGF21水平;HE染色提示肝脏脂肪变较模型组明显好转;与HF组比较,二甲双胍可增加肝脏AMPK-α及FGF21 mRNA表达(P<0.05),而adiponectin mRNA表达无明显变化(P>0.05),但脂肪组织adiponectin mRNA表达明显上调。结论与高脂喂养组比较,二甲双胍可有效减轻高脂诱导大鼠肝脏脂质沉积及外周胰岛素抵抗,推断其机制与二甲双胍通过AMPK途径上调肝脏FGF21 mRNA表达有关,但其并非直接作用于肝细胞,可能是通过刺激脂肪组织adiponectin分泌而发挥降脂及改善胰岛素抵抗的作用。

Adiponectin and its association with insulin resistance and type 2 diabetes

Adiponectin is an adipokine, which is expressed in adipose tissue and is thought to play an important role in glucose metabolism. Hypoadiponectinemia can cause reduction of fatty acid oxidation, decreased glucose uptake in skeletal muscle cells, and increased gluconeogenesis in hepatic cells. The level of plasma glucose can be increased. On the other hand, the decrease of fatty acid oxidation increases the level of free fatty acid （FFA）, which increases the insulin resistance, and then decreases the glucose uptake, which ultimately causes increased plasma glucose and type 2 diabetes （T2D）. This review describes the process from hypoadiponectinemia to T2D and the genesis of hypoadiponectinemia at a molecular level.

透析患者血浆Adiponectin水平和影响因素

目的观察维持性血液透析和腹膜透析患者血浆Adiponectin(ADPN)水平,探讨其相关影响因素。方法选择北京大学第三医院肾内科健康对照组20例,病情稳定的维持性血液透析患者30例,腹膜透析患者30例,ELISA方法测定3组研究对象的空腹血浆ADPN,每例透析患者测定血清白介素IL-6(IL-6)和肿瘤坏死因子(TNF-α),C反应蛋白,前白蛋白,转铁蛋白,血清甘油三酯,总胆固醇,计算KT/V,主观营养综合评估(SGA)透析患者的营养状况。结果①维持性腹膜透析患者血浆adiponectin水平较正常对照组明显升高(P=0.049),较血液透析组明显升高(P=0.007)[(2.335±1.673)mg/LVs(1.442±0.632)mg/LVs(1.256±0.613)mg/L],而血液透析组血浆ADPN水平较正常对照组差异无显著性(P>0.05);②腹膜透析患者体重指数(BMI)≥25kg/m2较BMI<25kg/m2其ADPN水平明显升高(P<0.01),SGA评分营养良好者较营养不良ADPN水平明显升高(P<0.01),多元回归分析ADPN的独立影响因素是BMI,回归方程为Y(ADPN)=-3.451+0.611X1(BMI);③Pearson相关分析表明血液透析患者ADPN水平与年龄负相关(r=-0.478,P=0.01),与透析充分性Kt/V正相关(r=0.518,P=0.016),与SGA评分负相关,但多元线性回归分析表明年龄﹑Kt/V是血液透析患者血浆ADPN水平的独立影响因素,其回归方程为Y(ADPN)=2.263-0.556X1(年龄)+0.403X2(Kt/V);④所有透析患者的血浆ADPN水平与超敏C反应蛋白,IL-6和TNF-α无显著相关,与血清甘油三酯,总胆固醇水平无显著相关。结论肾功能与透析治疗对血浆ADPN的水平调节只起很小的作用,腹膜透析患者的ADPN与体重指数正相关,血液透析患者的ADPN与年龄负相关,与透析充分性正相关。所有透析患者的营养水平与ADPN正相关,但不是独立影响因素,ADPN与透析患者炎症反应和血脂水平亦无明确相关性。

Fat cell-secreted adiponectin mediates physical exercise-induced hippocampal neurogenesis: an alternative anti-depressive treatment?

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.

Adiponectin as a novel biomarker for liver fibrosis

Adiponectin is known to play primary roles in the regulation of systemic glucose homeostasis and lipid metabolism. Interestingly, emerging evidence indicates beneficial effects of adiponectin on liver fibrosis; however, the exact mechanisms of this action remain unclear. Herein, we aimed to summarize the recent findings regarding the role of adiponectin in liver fibrogenesis and update the current comprehensive knowledge regarding usefulness of adiponectin-based treatments in liver fibrosis. Adiponectin has been demonstrated to have an anti-fibrotic action in the liver by blocking the activation of hepatic stellate cellmediated adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptoralpha pathways, which in turn diminish the expression of pro-fibrotic genes. In addition, hyperadiponectinemia was noted in patients with various chronic liver diseases(CLDs)-related liver fibrosis. An increase in circulating adiponectin levels was also found to be associated with the development of liver fibrosis, indicating a role of adiponectin as a non-invasive biomarker for predicting the progression of liver fibrosis. It is therefore reasonable to speculate that adiponectin may be developed as a new therapeutic candidate for the treatment of liver fibrosis. Nonetheless, future observations are still necessary to fully elucidate the extent of the effects of adiponectin onliver fibrotic outcomes, in order to modify adiponectin as an anti-fibrotic therapy that would speed up fibrosis reversal in patients with CLD.

Endocytosis of adiponectin receptor I through a clathrin- and Rab5-dependent pathway

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.