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adiponectin restores the obesity-induced impaired immunomodulatory function of mesenchymal stromal cells via glycolytic reprogramming

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Acta Pharmaceutica Sinica B 2024年第1期14卷 273-291页

作者： Duc-Vinh Pham Thi-Kem Nguyen Bao-Loc Nguyen Jong-Oh Kim Jee-Heon Jeong Inho Choi Pil-Hoon Park Department of Pharmacology Hanoi University of PharmacyHanoi 100000Viet Nam College of Pharmacy Yeungnam UniversityGyeongsan 38541Republic of Korea Department of Medical Biotechnology Yeungnam UniversityGyeongsan 38541Republic of Korea Research Institute of Cell Culture Yeungnam UniversityGyeongsan 38541Republic of Korea Department of Precision Medicine School of MedicineSungkyunkwan UniversitySuwon 16419Republic of Korea

Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells(MSC).However,it remains unclear what drives the compromised potency of obese MSC.In this study,we examined the involvement of adiponectin,an adipose tissuederived hormone,in obesity-induced impaired therapeutic function of MSC.Diet-induced obesity leads to a decrease in serum adiponectin,accompanied by impairment of survival and immunomodulatory effects of adipose-derived MSC(ADSC).Interestingly,priming with globular adiponectin(gAcrp)improved the immunomodulatory potential of obese ADSC.Similar effects were also observed in lean ADSC.In addition,gAcrp potentiated the therapeutic effectiveness of ADSC in a mouse model of DSS-induced colitis.Mechanistically,while obesity inhibited the glycolytic capacity of MSC,gAcrp treatment induced a metabolic shift toward glycolysis through activation of adiponectin receptor type 1/p38 MAPK/hypoxia inducible factor-1a axis.These findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.

关键词： adiponectin Adipose-derived stromal cells Colitis Glycolytic induction HIF1a Immunomodulation Mesenchymal stromal cells Obesity

adiponectin as a therapeutic target for diabetic foot ulcer

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World Journal of Diabetes 2023年第6期14卷 758-782页

作者： Mona Mohamed Ibrahim Abdalla Jaiprakash Mohanraj Sushela Devi Somanath Department of Physiology Human Biology DivisionSchool of MedicineInternational Medical UniversityKuala Lumpur 57000Malaysia Department of Biochemistry Human Biology DivisionSchool of MedicineInternational Medical UniversityKuala Lumpur 57000Malaysia Department of Microbiology School of MedicineInternational Medical UniversityKuala Lumpur 57000Malaysia

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.

关键词： Diabetic foot ulcer adiponectin Anti-inflammatory Adipose tissue Antioxidants Wound healing

adiponectin:friend or foe in obesity and inflammation

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Medical Review 2022年第4期2卷 349-362页

作者： Liping Luo Meilian Liu Department of Biochemistry and Molecular Biology University of New Mexico Health Sciences CenterAlbuquerqueNM 87131USA Department of Endocrinology Endocrinology Research CenterXiangya HospitalCentral South UniversityChangshaHunan Province 410008China

adiponectin is an adipokine predominantly produced by fat cells,circulates and exerts insulin-sensitizing,cardioprotective and anti-inflammatory effects.Dysregulation of adiponectin and/or adiponectin signaling is implicated in a number of metabolic diseases such as obesity,insulin resistance,diabetes,and cardiovascular diseases.However,while the insulin-sensitizing and cardioprotective effects of adiponectin have been widely appreciated in the field,the obesogenic and anti-inflammatory effects of adiponectin are still of much debate.Understanding the physiological function of adi-ponectin is critical for adiponectin-based therapeutics for the treatment of metabolic diseases.

关键词： adipogenesis adiponectin inflammation in-sulin sensitivity obesity

adiponectin gene polymorphisms and risk of gestational diabetes mellitus:A meta-analysis

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World Journal of Clinical Cases 2019年第5期7卷 572-584页

作者： Lin-Ting Huang Shi-Lan Wu Xin Liao Shu-Juan Ma Hong-Zhuan Tan Department of Epidemiology and Health Statistics Xiangya School of Public Health Central South University

BACKGROUND adiponectin(ADIPOQ) is an important factor involved in the regulation of both carbohydrate and lipid metabolism. Polymorphisms in the ADIPOQ gene are known to influence an individual's predisposition to metabolic syndrome and type 2 diabetes. Moreover, women with gestational diabetes mellitus(GDM) are at an increased risk of developing type 2 diabetes. Several studies have been conducted previously to assess the association between ADIPOQ polymorphisms and GDM; however, the results of the association are inconclusive.AIM To quantitatively evaluate the association between ADIPOQ +45 T/G, +276 G/T,and-11377 C/G polymorphisms and the risk of GDM.METHODS A systematic search of EMBASE, PubMed, CNKI, Web of Science, and WANFANG DATA was conducted up to October 20, 2018. We calculated merged odds ratios(ORs) with 95% confidence intervals(CIs) using a fixed-effects or random-effects model depending on the between-study heterogeneity to evaluate the association between AIDPOQ +45 T/G, +276 G/T, and-11377 C/G polymorphisms and the risk of GDM. Subgroup analysis was performed by ethnicity. Publication and sensitivity bias analyses were performed to test the robustness of the association. All statistical analyses were conducted using Stata 12.0.RESULTS Nine studies of +45 T/G included 1024 GDM cases and 1059 controls, five studies of +276 G/T included 590 GDM cases and 595 controls, and five studies of-11377 C/G included 722 GDM cases and 791 controls. Pooled ORs indicated that+45 T/G increased GDM risk in Asians(allelic model: OR = 1.47, 95%CI: 1.27-1.70,P = 0.000; dominant model: OR = 1.54, 95%CI: 1.27-1.85, P = 0.000; recessive model: OR=2.00, 95%CI: 1.43-2.85, P = 0.000), not in South Americans(allelic model: OR = 1.21, 95%CI: 0.68-2.41, P = 0.510; dominant model: OR = 1.13, 95%CI:,0.59-2.15, P = 0.710; recessive model: OR = 2.18, 95%CI: 0.43-11.07, P = 0.350).There were no significant associations between +276 G/T(allelic model: OR = 0.88,95%CI: 0.74-1.05, P = 0.158; dominant model: OR = 0.91, 95%CI: 0.65-1.2

关键词： Gestational diabetes mellitus Single nucleotide Polymorphism adiponectin Gene Meta-analysis

Phenotypic changes in the metabolic profile and adiponectin activity during seasonal fattening and hibernation in female Daurian ground squirrels(Spermophilus dauricus)

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Integrative Zoology 2022年第2期17卷 297-310页

作者： Yue REN Shiyi SONG Xinyu LIU Ming YANG College of life Sciences Shenyang Normal UniversityShenyangChina

Seasonal hibernation has provided an opportunity to study animals’phenotypic plasticity in adaptation to changing environment.In the present study focusing on the female Daurian ground squirrel(Spermophilus dauricus)-a well demonstrated seasonal hibernator-we examined their behavioral,morphological,and metabolic changes during fattening,hibernation,and emergence.Our data indicated high levels of food intake,fat deposition,and body mass increases during fattening compared to hibernation.The levels of serum glucose and triglycerides were also higher during fattening than during hibernation and emergence.Interestingly,although squirrels showed signs of obesity and elevated triglycerides in serum during fattening,triglyceride levels in the liver and skeletal muscles remained unchanged.Our data also indicated that adiponectin levels in serum and cerebrospinal fluid were different between fattening and hibernation.Levels of adiponectin receptor 1 in the skeletal muscle remained low during fattening but peaked in late hibernation.In contrast,adiponectin receptor 2 in the liver showed a steady increase during fattening,which was followed by a significant decrease at early hibernation.Our data indicate that adiponectin may play an important role in preventing heterotopic fat accumulation in a receptor-and organ-specific manner,as well as in facilitating the switch from glucose metabolism to lipid metabolism during fattening and hibernation in female Daurian ground squirrels.

关键词： adiponectin fattening hibernation liver metabolic adaptation muscle

adiponectin:a versatile player of innate immunity

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分子细胞生物学报:英文版 2016年第2期8卷 120-128页

作者： Yan Luo Meilian Liu Institute of Metabolism and Endocrinology Metabolic Syndrome Research Centerthe Second Xiangya HospitalCentral South UniversityChangsha 410011China Department of Biochemistry and Molecular Biology University of New Mexico Health Sciences CenterAlbuquerqueNM 87131USA

adiponectin acts as a key regulator of the innate immune system and plays a major role in the progression of inflammation and metabolic disorders.Macrophages and monocytes are representative components of the innate immune system,and their proliferation,plasticity,and polarization are a key component of metabolic adaption.Innate-like lymphocytes such as group 2 innate lymphoid cells(ILC2s),natural killer T(NKT)cells,and gamma delta T(gd T)cells are also members of the innate immune system and play important roles in the development of obesity and its related diseases.adiponectin senses metabolic stress and modulates metabolic adaption by targeting the innate immune system under physiological and pathological conditions.Defining the mechanisms underlying the role of adiponectin in regulating innate immunity is crucial to adiponectin-based therapeutic intervention.

关键词： adiponectin innate immunity macrophage innate-like lymphocyte

Compression loading of osteoclasts attenuated micro RNA-146a-5p expression,which promotes angiogenesis by targeting adiponectin

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Science China(Life Sciences) 2022年第1期65卷 151-166页

作者： Yue Wang Yunfei Zheng Weiran Li Department of Orthodontics Peking University School and Hospital of StomatologyBeijing 100081China

Osteoclastogenesis in alveolar bone induced by compression stress triggers orthodontic tooth movement.Compression stress also stimulates angiogenesis,which is essential for osteoclastogenesis.However,the effects of osteoclastogenesis induced by compression on angiogenesis are poorly understood.In vivo,we found the markers of angiogenesis increased during orthodontic bone remodeling.In vitro,osteoclast-derived exosomes increased proliferation,migration,and tube formation of human umbilical vein endothelial cells(HUVECs),as well as expression of vascular endothelial growth factor and CD31.The promotive effects of exosomes derived from compressed osteoclasts were greater than those derived from osteoclasts without compression.Next,we analyzed changes in the micro RNA transcriptome after compression stress and focused on micro RNA146 a-5 p(mi R-146 a),which was significantly decreased by compression.Transfection of an inhibitor of mi R-146 a stimulated angiogenesis of HUVECs while mi R-146 a mimics repressed angiogenesis.adiponectin(ADP)was confirmed to be a target of mi R-146 a by dual luciferase reporter assay.In HUVECs treated with exosomes,we detected increased ADP which promoted angiogenesis.Knockdown of ADP in HUVECs reduced the promotive effects of exosomes.Our results demonstrate that the decreased mi R-146 a observed in osteoclasts after compression promotes angiogenesis by targeting ADP,suggesting a novel method to interfere with bone remodeling induced by compression stress.

关键词： micro RNA-146a-5p adiponectin angiogenesis compression stress osteoclastogenesis exosomes

adiponectin signaling and function in insulin target tissues

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分子细胞生物学报:英文版 2016年第2期8卷 101-109页

作者： Hong Ruan Lily Q.Dong Department of Pharmacology University of Texas Health Science Center at San Antonio7703 Floyd Curl DriveSan AntonioTX 78229USA Department of Cell and Structural Biology University of Texas Health Science Center at San Antonio7703 Floyd Curl DriveSan AntonioTX 78229USA

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.

关键词： adiponectin insulin resistance cell signaling APPL1 APPL2 adiponectin receptor

adiponectin affects the mechanical responses in strips from the mouse gastric fundus

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World Journal of Gastroenterology 2018年第35期24卷 4028-4035页

作者： Eglantina Idrizaj Rachele Garella Giovanni Castellini Hermine Mohr Natalia S Pellegata Fabio Francini Valdo Ricca Roberta Squecco Maria Caterina Baccari Department of Experimental and Clinical Medicine Section of Physiological Sciences University of Florence Psychiatry Unit Department of Health Sciences University of Florence Institute for Diabetes and Cancer Helmholtz Zentrum München

AIM To investigate whether the adipocytes derived hormone adiponectin(ADPN) affects the mechanical responses in strips from the mouse gastric fundus. METHODS For functional experiments, gastric strips from the fundal region were cut in the direction of the longitudinal muscle layer and placed in organ baths containing KrebsHenseleit solution. Mechanical responses were recorded via force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrical field stimulation(EFS) was applied via two platinum wire rings through which the preparation was threaded. The effects of ADPN were investigated on the neurally-induced contractile and relaxant responses elicited by EFS. The expression of ADPN receptors, Adipo-R1 and Adipo-R2, was also evaluated by touchdown-PCR analysis. RESULTS In the functional experiments, EFS(4-16 Hz) elicited tetrodotoxin(TTX)-sensitive contractile responses. Addition of ADPN to the bath medium caused a reduction in amplitude of the neurally-induced contractile responses(P 0.05). The direct smooth muscle response to methacholine was not influenced by ADPN(P > 0.05). In carbachol precontracted strips and in the presence of guanethidine, EFS induced relaxant responses. Addition of ADPN to the bath medium, other than causing a slight and progressive decay of the basal tension, increased the amplitude of the neurally-induced relaxant responses(P < 0.05). Touchdown-PCR analysis revealed the expression of both Adipo-R1 and Adipo-R2 in the gastric fundus.CONCLUSION The results indicate for the first time that ADPN is able to influence the mechanical responses in strips from the mouse gastric fundus.

关键词： adiponectin adiponectin receptors Gastric motility Nitric oxide Non-adrenergic,non-cholinergic neurotransmission