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adipokines regulate mesenchymal stem cell osteogenic differentiation

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World Journal of Stem Cells 2023年第6期15卷 502-513页

作者： Zhong-Hua Xu Chen-Wei Xiong Kai-Song Miao Zhen-Tang Yu Jun-Jie Zhang Chang-Lin Yu Yong Huang Xin-Die Zhou Department of Orthopedics Jintan Hospital Affiliated to Jiangsu UniversityChangzhou 213200Jiangsu ProvinceChina Department of Orthopedics The Affiliated Changzhou Second People’s Hospital of Nanjing Medical UniversityChangzhou 213000Jiangsu ProvinceChina Changzhou Medical Center Nanjing Medical UniversityChangzhou 213000Jiangsu ProvinceChina Department of Orthopedics Gonghe County Hospital of Traditional Chinese MedicineHainan Tibetan Autonomous Prefecture 811800Qinghai ProvinceChina

Mesenchymal stem cells(MSCs)can differentiate into various tissue cell types including bone,adipose,cartilage,and muscle.Among those,osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies.Moreover,the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing.Recently,with the gra-dual recognition of adipokines,the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism,inflammation,immune regulation,energy disorders,and bone homeostasis.At the same time,the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely.Therefore,this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs,emphasizing bone formation and bone regeneration.

关键词： Mesenchymal stem cells adipokines Adipose tissue Osteogenic differentiation Osteogenesis Bone regeneration

Bo′s abdominal acupuncture improves disordered metabolism in obese type 2 diabetic rats through regulating fibroblast growth factor 21 and its related adipokines

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Journal of Traditional Chinese Medicine 2023年第6期43卷 1200-1208页

作者： QIN Xihui PANG Jianli XIONG Guan FENG Jie School of Pharmaceutical Sciences Guangxi Medical UniversityNanning 530021China Department of Endocrinology Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese MedicineNanning 530011China Department of Gynecology and obstetrics the Eighth People’s Hospital of NanningNanning 530007China

OBJECTIVE:To investigate the effect of Bo′s abdominal acupuncture(BOAA)on fibroblast growth factor 21(FGF21)and its related adipokines in type 2 diabetes mellitus(T2DM)rats.METHODS:This study established obese T2DM rat model by high-fat diet(HFD)with a dose of streptozotocin(STZ,30 mg/kg).Obese T2DM rats were randomly subdivided into four groups(n=10):negative,BOAA,conventional acupuncture(COA group)and metformin group(Met group)groups.The biochemical parameters,mRNAs,and proteins were analyzed using enzyme-lined immunoassays kits,quantitative polymerase chain reaction and Western blot.RESULTS:Treatment with BOAA attenuated the histopathological changes in visceral fat and restored the alterations in the levels of body weight,fasting blood glucose(FBG),homeostasis model assessment for insulin resistance(HOMA-IR).BOAA treatment significantly decreased the levels of triglyceride,total cholesterol,low density lipoprotein cholesterol,leptin,and increased the serum levels of high-density lipoprotein cholesterol,fibroblast growth factor 21(FGF21),adiponectin(ADP),peroxisome proliferator-activated receptorγ(PPAR-γ),C-peptide(C-P)in obese T2DM rats.Furthermore,BOAA treatment significantly increased the mRNA expressions of FGF21,ADP,leptin,PPAR-γ,PPAR-αand adenosine 5‘-monophosphate(AMP)-activated protein kinase(AMPK).Besides,BOAA treatment upregulated the protein expressions of fibroblast growth factor receptors3(FGFR3),PPAR-α,extracellular signal-regulated kinase(ERK),phosphorylated ERK(p-ERK),AMPK,p-AMPK,Liver kinase B1(LKB1),phosphorylated LKB1(p-LKB1),acetyl-CoA carboxylase(ACC)and phosphorylated ACC(p-ACC),while downregulated the protein expressions of FGF21 and PPAR-γin visceral fat.CONCLUSIONS:BOAA treatment reduced FBG and body weight,and improved insulin sensitivity through regulating FGF21 signaling pathway and its related adipokine in obese T2DM rats.

关键词： diabetes mellitus type 2 obesity fibroblast growth factors adipokines insulin resistance Bo′s abdominal acupuncture

Role of adipokines in sarcopenia

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Chinese Medical Journal 2023年第15期136卷 1794-1804页

作者： Wenhao Lu Wenjie Feng Jieyu Lai Dongliang Yuan Wenfeng Xiao Yusheng Li Department of Orthopaedics Xiangya HospitalCentral South UniversityChangshaHunan 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Burns and Plastic Surgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China Xiangya School of Medicine Central South UniversityChangshaHunan 410083China.

Sarcopenia is an age-related disease that mainly involves decreases in muscle mass,muscle strength and muscle function.At the same time,the body fat content increases with aging,especially the visceral fat content.Adipose tissue is an endocrine organ that secretes biologically active factors called adipokines,which act on local and distant tissues.Studies have revealed that some adipokines exert regulatory effects on muscle,such as higher serum leptin levels causing a decrease in muscle function and adiponectin inhibits the transcriptional activity of Forkhead box O3(FoxO3)by activating peroxisome proliferators-activated receptor-γcoactivator-1α(PGC-1α)and sensitizing cells to insulin,thereby repressing atrophy-related genes(atrogin-1 and muscle RING finger 1[MuRF1])to prevent the loss of muscle mass.Here,we describe the effects on muscle of adipokines produced by adipose tissue,such as leptin,adiponectin,resistin,mucin and lipocalin-2,and discuss the importance of these adipokines for understanding the development of sarcopenia.

关键词： Sarcopenia adipokines Leptin Adiponectin Lipocalin-2 Visfatin Resistin

The influence of resistance training on adipokines in post-menopausal women:A brief review

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Sports Medicine and Health Science 2022年第4期4卷 219-224页

作者： Tomas Chapman-Lopez Dylan Wilburn Emma Fletcher Kathleen Adair Ahmed Ismaeel Jeffery Heileson Andrew Gallucci LesLee Funderburk Panagiotis Koutakis Jeffrey S.Forsse Department of Health Human Performance and Recreation Baylor UniversityWacoTX76706USA Clinical Muscle Biology Lab Biology DepartmentBaylor UniversityWacoTX76798USA Department of Physiology University of Kentucky780 Rose St.MS508LexingtonKY40536USA Human Sciences and Design Baylor UniversityWacoTX76798USA

The onset of menopause elicits changes in body composition that negatively influence adipokine levels.Consequently,various health risk factors(e.g.,cardiovascular disease,osteoporosis,physical inactivity,obesity,arterial hypertension,hypercholesterolemia,sarcopenia)are influenced by adipokines due to changes in body composition after menopause.Thus,improvements in body composition are considered the primary influencer of adipokines.Though several therapeutic interventions(e.g.,medication,diet,meditation,exercise)are employed to target changes in body composition,resistance training appears to be more effective in positively improving body composition through changes in lean-muscle mass/fat-mass ratio.However,due to the lack of research,very little is known about adipokines'anti/inflammatory response in postmenopausal women after completing resistance training.Most resistance training studies in postmenopausal women have focused on leptin,adiponectin,and resistin,with limited research assessing other adipokines that are important in metabolic regulation and inflammatory processes.Additionally,the consistency of resistance training protocols as an intervention is not standardized or fully recognized.Therefore,the focus of this review is to establish a more comprehensive understanding of the benefits of resistance training on influencing adipokine levels based on changes to total body composition in postmenopausal women.

关键词： adipokines Post-menopause Resistance training Body composition

Exercise training-induced changes in exerkine concentrations may be relevant to the metabolic control of type 2 diabetes mellitus patients:A systematic review and meta-analysis of randomized controlled trials

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Journal of Sport and Health Science 2023年第2期12卷 147-157页

作者： Antonio García-Hermoso Robinson Ramírez-Vélez Javier Díez Arantxa González Mikel Izquierdo Navarrabiomed Public University of Navarra(UPNA)Health Research Institute of Navarra(IdiSNA)University Hospital of NavarraPamplona 310008Spain CIBER of Frailty and Healthy Aging(CIBERFES) Carlos Ⅲ Institute of HealthMadrid 28029Spain Institute for Health Research of Navarra(IDISNA) Pamplona 31008Spain Program of Cardiovascular Diseases Center for Applied Medical ResearchUniversity of NavarraPamplona 31008Spain Centre for Biomedical Research in Cardiovascular Disease Network Carlos Ⅲ Institute of HealthMadrid 28029Spain Departments of Nephrology and Cardiology University of Navarra ClinicPamplona 31008Spain

Background:This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription.Methods:A systematic search for relevant studies was performed in 3 databases.Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included:adiponectin,apelin,brain-derived neurotrophic factor,fetuin-A,fibroblast growth factor-21,follistatin,ghrelin,interleukin(IL)-6,IL-8,IL-10,IL-15,IL-18,leptin,myostatin,omentin,resistin,retinol-binding protein 4,tumor necrosis factor-α,and visfatin.Results:Forty randomized controlled trials were selected for data extraction(n=2160).Exercise training induces changes in adiponectin,fetuin-A,fibroblast growth factor-21,IL-6,IL-10,leptin,resistin,and tumor necrosis factor-a levels but has no significant effects on apelin,IL-18,and ghrelin compared to controls.Physical exercise training favored large and positive changes in pooled exerkines(i.e.,an overall effect size calculated from several exerkine s)(Hedge’s g=1.02,95%confidence interval(95%CI):0.76-1.28),which in turn were related to changes in glycated hemoglobin(mean difference(MD)=-0.81%,95%CI:-0.95%to-0.67%),fasting glucose(MD=-23.43 mg/dL,95%CI:-30.07 mg/dL to-16.80 mg/dL),waist circumference(MD=-3.04 cm,95%CI:-4.02 cm to-2.07 cm),and body mass(MD=-1.93 kg,95%CI:-2.00 kg to-1.86 kg).Slightly stronger effects were observed with aerobic,resistance,or high-intensity interval protocols at moderate-to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per session.Conclusion:Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.

关键词： adipokines Exercise training Hepatokines Myokines

Modified Linggui Zhugan Decoction Ameliorates Glycolipid Metabolism and Inflammation via PI3K-Akt/m TOR-S6K1/AMPK-PGC-1α Signaling Pathways in Obese Type 2 Diabetic Rats

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Chinese Journal of Integrative Medicine 2022年第1期28卷 52-59页

作者： SUN Jia-pan SHI Lin WANG Fang QIN Jian KE Bin Department of Traditional Chinese Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou(510080)China Department of Traditional Chinese Medicine Zhujiang Hospital of Southern Medical UniversityGuangzhou(510280)China Department of Oncology the First Affiliated HospitalSun Yat-sen UniversityGuangzhou(510080)China Department of Traditional Chinese Medicine the Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen(518107)Guangdong ProvinceChina Department of VIP Ward Sun Yat-sen University Cancer CenterGuangzhou(510060)China

Objective: To investigate the protective effects of modified Linggui Zhugan Decoction(MLZD), a traditional Chinese medicine formula, on obese type 2 diabetes mellitus(T2 DM) rats. Methods:Fifty Sprague-Dawley rats were randomly divided into 5 groups by a random number table, including normal, obese T2 DM(ob-T2 DM), MLZD low-dose [MLDZ-L, 4.625 g/(kg·d)], MLZD middle-dose [MLD-M,9.25 g/(kg·d) ] and MLZD high-dose [MLD-H, 18.5 g/(kg·d)] groups,10 rats in each group. After 4-week intervention, blood samples and liver, pancreas, muscle tissues were collected to assess the insulin resistance(IR), blood lipid, adipokines and inflammation cytokines. The alteration of phosphatidylinositol 3 kinase(PI3 K)-protein kinase B(PKB or Akt)/the mammalian target of rapamycin(mTOR)-ribosome protein subunit 6 kinase 1(S6 K1)/AMP-activated protein kinase(AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC-1α) pathways were also studied. Results: MLZD dose-dependently reduced fasting blood glucose,fasting insulin, homeostasis model of assessment for IR index and increased insulin sensitive index compared with ob-T2 DM rats(Padipokines and inflammatory cytokines were observed with a raised level of adiponectin and a reduced level of leptin, resistin, tumor necrosis factor-α and interleukin-6(P<0.05 or P<0.01). MLZD regulated the PI3 K-Akt/mTOR-S6 K1/AMPK-PGC-1α pathways and restored the tissue structure of liver and pancreas(P<0.05 or P<0.01). Conclusions: MLZD ameliorated glycolipid metabolism and inflammation, which may be attributed to the regulation of PI3 K-Akt/mTOR-S6 K1/AMPK-PGC-1α pathways.

关键词： Chinese medicine obesity type 2 diabetes mellitus glycolipid metabolism adipokines inflammation

Protective Roles of Shilajit in Modulating Resistin,Adiponectin,and Cytokines in Rats with Non-alcoholic Fatty Liver Disease

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Chinese Journal of Integrative Medicine 2022年第6期28卷 531-537页

作者： Baran Ghezelbash Nader Shahrokhi Mohammad Khaksari Gholamreza Asadikaram Maryam Shahrokhi Sara Shirazpour Physiology Research Center Kerman University of Medical SciencesKerman***Iran Endocrinology and Metabolism Research CenterKerman University of Medical SciencesKerman***Iran Department of Biochemistry School of MedicineKerman University of Medical SciencesKerman***Iran Department of Medical Science School of DentistryShiraz University of Medical SciencesShiraz713414336Iran Department of Physiology and Pharmacology Faculty of MedicineKerman University of Medical SciencesKerman***Iran

Objective:To evaluate the effect of Shilajit,a medicine of Ayurveda,on the serum changes in cytokines and adipokines caused by non-alcoholic fatty liver disease(NAFLD).Methods:After establishing fatty liver models by feeding a high-fat diet(HFD)for 12 weeks,35 Wistar male rats were randomly divided into5 groups,including control(standard diet),Veh(HFD+vehicle),high-dose Shilajit[H-Sh,HFD+250 mg/(kg·d)Shilajit],low-dose Shilajit[L-Sh,HFD+150 mg/(kg·d)Shilajit],and pioglitazone[HFD+10 mg/(kg·d)pioglitazone]groups,7 rats in each group.After 2-week of gavage administration,serum levels of glucose,insulin,interleukin1 beta(IL-1β),IL-6,IL-10,tumor necrosis factor-alpha(TNF-α),adiponectin,and resistin were measured,and insulin resistance index(HOMA-IR)was calculated.Results:After NAFLD induction,the serum level of IL-10 significantly increased and serum IL-1β,TNF-αlevels significantly decreased by injection of both doses of Shilajit and pioglitazone(P<0.05).Increases in serum glucose level and homeostasis model of HOMA-IR were reduced by L-Sh and H-Sh treatment in NAFLD rats(P<0.05).Both doses of Shilajit increased adiponectin and decreased serum resistin levels(P<0.05).Conclusion:The probable protective role of Shilajit in NAFLD model rats may be via modulating the serum levels of IL-1β,TNF-α,IL-10,adipokine and resistin,and reducing of HOMA-IR.

关键词： non-alcoholic fatty liver disease Shilajit adipokines cytokines glucose insulin dietary supplement Ayurvedic medicine

Pathophysiology of obesity and its associated diseases

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药学学报:英文版 2023年第6期13卷 2403-2424页

作者： Xin Jin Tingting Qiu Li Li Rilei Yu Xiguang Chen Changgui Li Christopher G.Proud Tao Jiang School of Medicine and Pharmacy Ocean University of China and Laboratory for Marine Drugs and BioproductsQingdao National Laboratory for Marine Science and TechnologyQingdao 266100China Shandong Provincial Key Laboratory of Metabolic Diseases Qingdao Key Laboratory of GoutAffiliated Hospital of Qingdao University Medical CollegeQingdao UniversityQingdao 266100China Lifelong Health Theme South Australian Health and Medical Research InstituteNorth TerraceAdelaide SA 5000Australia College of Marine Life Sciences Ocean University of ChinaQingdao 266100China Shandong Laboratory of Yantai Drug Discovery Bohai Rim Advanced Research Institute for Drug DiscoveryYantai 264117China

The occurrence of obesity has increased across the whole world. Many epidemiological studies have indicated that obesity strongly contributes to the development of cancer, cardiovascular diseases, type 2 diabetes, liver diseases and other disorders, accounting for a heavy burden on the public and on health-care systems every year. Excess energy uptake induces adipocyte hypertrophy, hyperplasia and formation of visceral fat in other non-adipose tissues to evoke cardiovascular disease, liver diseases. Adipose tissue can also secrete adipokines and inflammatory cytokines to affect the local microenvironment,induce insulin resistance, hyperglycemia, and activate associated inflammatory signaling pathways. This further exacerbates the development and progression of obesity-associated diseases. Although some progress in the treatment of obesity has been achieved in preclinical and clinical studies, the progression and pathogenesis of obesity-induced diseases are complex and unclear. We still need to understand their links to better guide the treatment of obesity and associated diseases. In this review, we review the links between obesity and other diseases, with a view to improve the future management and treatment of obesity and its co-morbidities.

关键词： Obesity Cardiovascular disease Liver disease Insulin resistance adipokines Inflammation MNK Lipid accumulation

Intestinal microbiota in the treatment of metabolically associated fatty liver disease

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World Journal of Clinical Cases 2022年第31期10卷 11240-11251页

作者： Ji-Shuai Wang Jin-Chun Liu Shanxi Medical University Taiyuan 030001Shanxi ProvinceChina Department of Gastroenterology The First Hospital of Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina

Metabolically associated fatty liver disease (MAFLD) is a common cause ofchronic liver disease, the hepatic manifestation of metabolic syndrome. Despitethe increasing incidence of MAFLD, no effective treatment is available. Recentresearch indicates a link between the intestinal microbiota and liver diseases suchas MAFLD. The composition and characteristics of the intestinal microbiota andtherapeutic perspectives of MAFLD are reviewed in the current study. Animbalance in the intestinal microbiota increases intestinal permeability andexposure of the liver to adipokines. Furthermore, we focused on reviewing thelatest "gut-liver axis" targeted therapy.

关键词： Intestinal microbiota Metabolically associated fatty liver disease Gut-liver axis adipokines Therapy