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第十二届全国免疫学学术大会

作者： Fang Sijie Huang Yazhuo Zhong Sisi Li Yangyang Li Dan Zhou Huifang Li Bin Fan Xianqun Shanghai Ninth People's Hospital Shanghai JiaoTong University School of Medicine Shanghai Institute of Immunology Shanghai JiaoTong University School of Medicine

Context:Th17 cells are correlated with many human autoimmune disorders including Graves’ disease,and may play key roles in the pathogenesis of Graves’ orbitopathy(GO).Objective:To study the phenotype of Th17 cells in patients with GO and healthy subjects,investigate the fibrosis and adipogenesis in orbital fibroblasts(OFs) modulated by IL-17 A,and determine the interaction between Th17 cells and OFs.Design/Setting/Participants:Blood samples and orbital tissues from GO patients and healthy controls were collected.Main Outcome Measures:We conducted multi-color flow cytometry,immunohistochemical and immunofluorescent stainings,Western blotting,Pathscan intracellular signaling assay,Luminex and enzyme-linked immunosorbent assays,and protein mass spectrum.Results:IFN-γ and IL-22-expressing Th17 cells are increased in GO patients,which are positively related to clinical activity score.Costimulatory molecules are highly expressed in GO orbits and the majority of GO OFs are CD90.IL-17 A promotes TGF-β-induced fibrosis in CD90 OFs while impedes 15-d-PGJ-induced adipogenesis in CD90OFs.Th17 cells promote pro-inflammatory cytokine secretion in both CD90 and CD90OFs.Meanwhile,both CD90 and CD90OFs contribute to Th17 cell differentiation through prostaglandin E production,which can be attenuated by indomethacin.Furthermore,Th17 cells up-regulate costimulatory molecule expression on OFs.Conclusion:Our findings unravel the pathogenicity of IL-17 A in the initiation and progression of GO.In-depth interpretation of the molecular basis of OFs delineated by CD90 and Th17-OF interaction will help to afford a novel approach to better therapeutic strategies for GO.

关键词： Graves’ orbitopathy Thl7 cell fibrosis adipogenesis

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Cold-induced beige adipogenesis alter lipid metabolism and expression of inflammatory adipokines

Cold-induced beige adipogenesis alter lipid metabolism and e...

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中国生理学会第24届全国会员代表大会暨生理学学术大会

作者：贾如 Xiao Luo Yuxiang Wang Chang Lu Ke Li Caixia Lin Jianqun Yan 西安交通大学 Department of Physiology and Pathophysiology Xi'an Jiaotong University Health Science Center

Two types of adipose tissue are present in mammals,white and brown（WAT and BAT）.While WAT is an energy storage depot,BAT dissipates energy via the mitochondrialuncoupling protein UCP1,defending against hypothermia and obesity.Recently,UCP1 expressing adipocytes with a different lineage to classical brown adipocytes have been found in WAT.These adipocytes have been named beige cell or brown in white（brite）cells and they become more prominent upon prolonged stimulation by cold or beta3-adrenergic receptor agonists that increase intracellular cyclic AMP.Beige cells may represent a therapeutic target to counteract obesity.Although the gene expression of beige cells has been reported to be distinct from those of BAT or WAT,it remains unclear whether the expression of inflammatory adipokines is changed in beige cells.It also has not been well documented whether the body fat composition and lipid metabolism in these mice are altered during cold-induced beige adipogenesis.In this study,using C57BL/6J male mice,we demonstrated that 5-day cold exposure increased food intake dramatically（2.5-fold increase;P＜0.001;n=10）.Of interest,there was no significant differences in body weight and fat percentage between cold and control groups.The unchanged fat percentage was evident in the visceral and subcutaneous depots.However,the amount of interscapular BAT was significantly increase in cold-exposed relative to control mice（P＜0.05;n=10）.Furthermore,the size of both inguinal WAT and interscapular BAT was reduced in the cold-exposed mice,and the cells acquired a multilocular appearance（determined by HE staining）.The m RNA and protein expression of brown markers also indicated that the beige adipogenesis was happend in subcutaneous WAT.Notably,the lipid metabolism was improved in cold-exposed mice during beige adipogenesis.Although the blood glucose was unexpected increase,the circulating levels of both triglycerides and cholesterol decreased substantially in cold-exposed mice compared with control mice（P＜0.01;n=10）.Interestly,the ex

关键词： Beige cell Inflammatory adipokines Cold-induced Lipid matabolism adipogenesis

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A fast and highly efficient hiPSCs-Adipocytes differentiation method:patient specific cell models for adipogenesis and obesity research

A fast and highly efficient hiPSCs-Adipocytes differentiatio...

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第十三届江浙沪儿科学术会议暨2016年浙江省医学会儿科...

作者： Chenbo Ji Yuhui Ni Yaping Zhao Xianwei Cui Lianghui You Xing Wang Jiwu Wang Xirong Guo Nanjing Maternity and Child Health Care Hospital

Obesity epidemic is a growing global health threat.So far there is no safe and effective way to prevent obesity,as weight loss does not simply depend on diet or physical exercises.Obesity is characterized by an excessive accumulation of adipose tissue,therefore understanding the biological features of adipocytes is one of the keys to find the cure for obesity.Several in vitro models,such as 3 T3-L1,primary preadipocytes or some adult multipotent stem cells,contribute to our understanding of adipogenesis and the mechanisms of obesity.However,they are either murine origin cell lines,or primary cells withlimited expansion,which caused many contradictory results.In present study,we developed an improved method to get human induced pluripotent stem cells(hiPSCs)drived mesenchymal stem cells(MSCs) with high capacity of adipocyte differention(80-95%efficiency) after one day adipocyte differentiation treatments.The gene expression signatures of the adipocytes differentiated from the hiPSCs-MSCs is highly similar to primary mature adipocytes,with sensitive insulin response and function of adipokines secretion.Our previous study demonstrated that C10 orf116 and miR-148 a facilitated adipogenesis in primary preadipocyte or MSCs.We use these two factors to test the application of our newly developed hiPSCsMSCs-Adipocyte model in adipogenesis research.In addition,by comparing iPSCs lines from donors with different body mass index(BMI),we found the efficiency of adipogenic differention were highly related to BMI of the donors.In conclusion,this hiPSCs-MSCs-Adipocyte model we developed is fast,highly efficient,and with patient specific genetic background,which should be a great tool for adipogenesis research and other obesity mechanism or clinical research.

关键词： hiPSCs adipogenesis Obesity

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GSK3β activity that can be regulated by AICAR via stimulated AKT in preadipocytes is involved in the regulation of adipogenesis, glucose metabolism and insulin action in adipocytes

GSK3β activity that can be regulated by AICAR via stimulate...

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中国生物化学与分子生物学会2016年全国学术会议

作者： Li Wang Lijun Di Metabolomics Core Faculty of Health Sciences University of Macau Faculty of Health Sciences University of Macau

adipogenesis is a tightly regulated cellular differentiation process and the understanding of mechanism and manipulation of adipogenesis might contribute to a reduction in the burden of obesity and diabetes.Multiple transcription factors and signaling pathways are involved in the regulation of adipogenesis.Here we report that in preadipocytes,AMP-activated protein kinase activator,5-aminoimidazole-4-carboxamide ribonucleoside(AICAR)can activate AMPK to increase GSK3β

关键词： AICAR GSK3 AKT adipogenesis Glucose uptake

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Leucine signaling in the pathogenesis of type 2 diabetes and obesity

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World Journal of Diabetes 2012年第3期3卷 38-53页

作者： Bodo C Melnik Department of Dermatology Environmental Medicine and Health TheoryUniversity of Osnabrück

Epidemiological evidence points to increased dairy and meat consumption,staples of the Western diet,as major risk factors for the development of type 2 diabetes(T2D).This paper presents a new concept and comprehensive review of leucine-mediated cell signaling explaining the pathogenesis of T2D and obesity by leucine-induced over-stimulation of mammalian target of rapamycin complex 1(mTORC1).mTORC1,a pivotal nutrient-sensitive kinase,promotes growth and cell proliferation in response to glucose,energy,growth factors and amino acids.Dairy proteins and meat stimulate insulin/insulin-like growth factor 1 signaling and provide high amounts of leucine,a primary and independent stimulator for mTORC1 activation.The downstream target of mTORC1,the kinase S6K1,induces insulin resistance by phosphorylation of insulin receptor substrate-1,thereby increasing the metabolic burden of β-cells.Moreover,leucine-mediated mTORC1-S6K1-signaling plays an important role in adipogenesis,thus increasing the risk of obesity-mediated insulin resistance. High consumption of leucine-rich proteins explains exaggerated mTORC1-dependent insulin secretion, increased β-cell growth and β-cell proliferation promoting an early onset of replicative β-cell senescence with subsequent β-cell apoptosis.Disturbances of β-cell mass regulation with increased β-cell proliferation and apoptosis as well as insulin resistance are hallmarks of T2D,which are all associated with hyperactivation of mTORC1.In contrast,the anti-diabetic drug metformin antagonizes leucine-mediated mTORC1 signaling.Plant-derived polyphenols and flavonoids are identified as natural inhibitors of mTORC1 and exert anti-diabetic and anti-obesity effects.Furthermore,bariatric surgery in obesity reduces increased plasma levels of leucine and other branched-chain amino acids.Attenuation of leucine-mediated mTORC1 signaling by defining appropriate upper limits of the daily intake of leucine-rich animal and dairy proteins may offer a great chance for the prevention of T2D and obesity,as well as

关键词： adipogenesis Dairy proteins Diabetes Leucine Meat Mammalian target of rapamycin com- plex 1 Obesity

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Distinction of white,beige and brown adipocytes derived from mesenchymal stem cells

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World Journal of Stem Cells 2014年第1期6卷 33-42页

作者： Anna Park Won Kon Kim Kwang-Hee Bae Research Center for Integrated Cellulomics KRIBB Department of Biological Sciences Korea Advanced Institute of Science and Technology

Adipose tissue is a major metabolic organ, and it has been traditionally classified as either white adipose tissue(WAT) or brown adipose tissue(BAT). WAT and BAT are characterized by different anatomical locations, morphological structures, functions, and regulations. WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold- or diet-induced thermogenesis. Recently, brownlike adipocytes were discovered in WAT. These brownlike adipocytes that appear in WAT are called beige or brite adipocytes. Interestingly, these beige/brite cells resemble white fat cells in the basal state, but they respond to thermogenic stimuli with increased levels of thermogenic genes and increased respiration rates. In addition, beige/brite cells have a gene expressionpattern distinct from that of either white or brown fat cells. The current epidemic of obesity has increased the interest in studying adipocyte formation(adipogenesis), especially in beige/brite cells. This review summarizes the developmental process of adipose tissues that originate from the mesenchymal stem cells and the features of these three different types of adipocytes.

关键词： White adipocytes Brown adipocytes Beige/ brite adipocytes Mesenchymal stem cells adipogenesis Thermogenesis Browning

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EVI1 Mediated Stimulation of 3T3-L1 Preadipocyte Differentiation Is CtBP Dependent

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Yangtze Medicine 2017年第3期1卷 133-147页

作者： M. J. Ireland M. Al-Hasan J. A. Craft A. Graham C. Bartholomew Department of Life Sciences School of Health & Life Sciences Glasgow Caledonian University City Campus Glasgow Scotland

Myelodysplasia syndrome 1 (MDS1) and Ecotropic viral integration site 1 (EVI1) complex (MECOM) locus encode multiple isoforms of the EVI1 protein that are essential for normal vertebrate development and when inappropriately expressed play a significant role in malignancy and in particular leukaemias. However, the function of individual EVI1 isoforms is not fully understood. Recently, EVI1 or PRDM3, which is structurally closely related to the brown adipose tissue determining factor PRDM16, was shown to be required for differentiation of adipocytes. In this study, we show that 3T3-L1 preadipocytes sustain expression of all Evi1 isoforms examined, including Mds1-Evi1, Evi1FL, Evi1Δ324, Evi1FL + 9 and Evi1Δ105 throughout the adipogenesis differentiation programme. We also show that differentiation markers are enhanced by enforced expression of either Evi1, Evi1FL + 9 or Evi1Δ105 isoforms. Interestingly 3T3-L1 differentiation markers are also moderately enhanced by enforced expression of Evi1Δ324, which lacks part of the N-ter-minal zinc finger domain (ZF1), demonstrating a biological activity for this particular isoform. Enforced expression of an Evi1 mutant lacking C-terminal binding protein (CtBP) co-repressor protein binding activity fails to stimulate 3T3-L1 differentiation markers and may have dominant negative activity, causing partial inhibition of this developmental programme. These studies show that multiple EVI1 isoforms are expressed in adipocytes and can stimulate adipogenic markers in a manner that is partially independent of the ZF1 DNA binding domain but fully dependent upon interaction with co-repressor CtBP proteins.

关键词： MECOM PRDM3 EVI1 Isoforms C-Terminal Binding Proteins adipogenesis

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Effects of the Ratio of Lysine to Digestible Energy Level in the Diet on the Expression and Activity of Transcription Factors Involved in Lipogenesis in Rongchang Pigs

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Journal of Animal Science and Biotechnology 2010年第3期1卷 165-174页

作者： Yuan Lu Xiaolei Yang Defa Li Jingdong Yin Ministry of Agriculture Feed Industry Centre State Key Laboratory of Animal Nutrition China Agricultural University Beijing 100193 China College of Animal Science and Medicine Inner Mongolia Agricultural University Huhehot Inner Mongolia010018 China

This study was conducted to determine the effects of varying the ratio of lysine to digestible energy level On the activity and gene expression of the transcription factors peroxisome proliferator-activated receptor-γ （PPAR-γ） and CCAAT/enhancer-binding protein-or and -β （C/EBP-α and C/EBP-β） to better understand the regulatory mechanisms controlling adipogenesis in fat and muscle tissue of the Rongchang pig. A total of 144 castrated Rongchang pigs weighing approximately 20 kg were used in a 2 ×2 factorial design experiment. Diets were formulated to contain a high （14.22 MJ/kg） or low （13.11 MJ/kg） digesti- ble energy （DE） level. Within each energy level, pigs were fed diets containing a high lysine： DE ratio （0.67,0. 53, or 0. 42） or a low lysine ： DE ratio （0.49,0.38 ,or 0.30） during the periods from 20 to 50 kg, 50 to 80 kg, and 80 kg to slaughter, respectively. Each diet was fed to six replicate pens, each containing nine pigs. When the pigs reached average live weights of 20,35,60, and 90 kg ,one pig from each of the replicates was chosen at random and slaughtered.Samples of back fat and longissimus dorsi muscle were collected for the assessment of transcriptional factor. The results showed that feeding a high DE level significantly increased （ P 〈 0.05 ） the expression of PPAR-T at 60 and 90 kg in muscle and at 35,60, and 90 kg in back fat. Energy level also significantly increased the expression of C/EBP-fl at 35 and 60 kg in both muscle and back fat （ P 〈 0.05 ）. Higher dieta- ry lysine increased the expression of C/EBP-fl in muscle at 35 and 90 kg （ P 〈 0.05）, but decreased the expression in back fat at 35 （P = 0.03 ） and 90 kg （P = 0.09）. The lysine level increased the expression of PPAR-3~ in muscle at 60 kg only. Energy level and lysine content had no significant effects on promote the activity of PPAR-γ, C/EBP-α, or C/EBP-β either in muscle or in back fat at any level of the body weights tested. Collectively, these data indicated that dietary energy density and lysine level were equally important for

关键词： activity adipogenesis digestible energy gene expression lysine pigs transcription factors

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Antioxidant, Enzyme Inhibitory and Anti-Obesity Potential of Sorrel Calyx Extracts in 3T3-L1 Adipocytes

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Food and Nutrition Sciences 2015年第5期6卷 452-465页

作者： E. Mutai R. Sunkara Jorge Vizcarra L. T. Walker M. Verghese Alabama A&M University Normal AL USA

Hibiscus sabdariffa L. (sorrel) has been widely used in the development of tropical beverages and folk medicine. This study’s objective was to investigate the anti-obesity potential of sorrel calyx extracts (methanol and water) on 3T3-L1 adipocyte cells. Phytochemical content, antioxidant potential as DPPH (1, 1-Diphenyl-2-picrylhydrazyl) radical scavenging activity and ferric reducing antioxidant power (FRAP) and enzyme (α-glucosidase, α-amylase, and pancreatic lipase) inhibitory activities were determined in sorrel methanol extracts (SME) and sorrel water extracts (SWE). Effect of SWE and SME on lipid accumulation, lipolysis and apoptosis were tested in 3T3-L1 adipocyte differentiation and maintenance stage of cells at selected concentrations (200 - 1000 μg/ml) was studied. The total phenolic (GAE mg/100g dry weight) and total flavonoid (mg catechin equi/ 100g dry weight) contents in SME and SWE were 158.31 and 317.27 and 90.77 and 100.08. DPPH% inhibition (IC-50-mg/ml) and FRAP (mmol Fe [II]/100g dry weight) were 0.82 and 0.33 and 1799.13 and 2296.38 for SWE and SME, respectively. SME and SWE inhibited α-glucosidase, α-amylase, and pancreatic lipase activities by more than 40% at 4mg/ml. Significant (p < 0.05) reduction in lipid accumulation and increased glycerol release in 3T3-L1 cells was observed at concentrations ranged from 600 mg/ml of both extracts. Treating cells with SME-1000 μg/ml at differentiation resulted inhibition (p < 0.05) of lipid accumulation by 45% compared to untreated cells. Highest (p < 0.05) (35%) decrease in triglyceride content as well as higher glycerol release was seen in cells exposed to SME at the differentiation stage. Sorrel extracts induced apoptosis in adipocytes at higher concentrations with prominent effect of treating cells at differentiation stage. The results of this study showed effect of sorrel extracts in reduction of lipid accumulation and increase in lipolysis of 3T3-L1 cells.

关键词： Sorrel Phytochemicals adipogenesis Adipocytes Lipolysis Antioxidant

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3,4-Oxo-isopropylidene-shikimic acid promotes adiopkine expression during murine 3T3-L1 fibroblast differentiation into adipocytes

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Journal of Traditional Chinese Medical Sciences 2014年第2期1卷 120-125页

作者： Shifen Dong Naomi Yasui Hiroko Negishi Ming Gao Yukio Yamori Katsumi Ikeda Jianning Sun Department of Pharmacology School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing 100029China School of Pharmacy and Pharmaceutical Sciences Mukogawa Women’s University11-68Nishinomiya 663-8179Japan Institute for World Health Development Mukogawa Women’s University11-68Nishinomiya 663-8179Japan

Objective:3,4-Oxo-isopropylidene-shikimic acid(ISA),a derivative of shikimic acid,has exhibited ameliorative effect on cognitive impairment in experimental animal models of dementia.This study investigated the effect of ISA on lipid accumulation and adipokine secretion during differentiation of 3T3-L1 fibroblasts to adipocytes.Methods:3T3-L1 cells were cultured and treated with ISA(50e800 mM)from days 3e8.Lipid accumulation and triglyceride content were measured.Gene expression of adipokines(adiponectin,leptin,and resistin),CCAAT/enhancer binding protein(C/EBP)b,C/EBP a and peroxisome proliferator-activated receptor g(PPAR g)and PPAR target genes,including adipocyte fatty acid binding protein(aP2)and fatty acid synthase(FAS)were investigated.Results:ISA promoted 3T3-L1 fibroblast differentiation to adipocytes and increased triglyceride content by 26%.On mechanistic levels,ISA increased expressions of C/EBP b,PPAR g,C/EBP a,aP2 and FAS.Moreover,ISA stimulated expressions of adipokines secreted by adipocytes,including adiponectin,leptin,and resistin.Conclusions:These findings demonstrated that ISA promoted adipogenesis by up-regulating expressions of C/EBP b,PPAR g,C/EBP a,aP2 and FAS,and also stimulated adipokines during adipocyte differentiation.Further study should clarify the relationship between stimulation of adipokines and cognitive enhancing effect of ISA.

关键词： 3,4-Oxoisopropylideneshikimic acid 3T3-L1 fibroblasts Adipocytes adipogenesis Adipokines

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