Human adipocyte function is impacted by mechanical cues
Fibrosis is a hallmark of human white adipose tissue (WAT) during obesity‐induced chronic inflammation. The functional impact of increased interstitial fibrosis (peri‐adipocyte fibrosis) on adjacent adipocytes remains unknown. Here we developed a novel in vitro 3D culture system in which human adipo...
Saved in:
| Published in | The Journal of pathology Vol. 233; no. 2; pp. 183 - 195 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Chichester, UK
John Wiley & Sons, Ltd
01.06.2014
Wiley Subscription Services, Inc |
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Fibrosis is a hallmark of human white adipose tissue (WAT) during obesity‐induced chronic inflammation. The functional impact of increased interstitial fibrosis (peri‐adipocyte fibrosis) on adjacent adipocytes remains unknown. Here we developed a novel in vitro 3D culture system in which human adipocytes and decellularized material of adipose tissue (dMAT) from obese subjects are embedded in a peptide hydrogel. When cultured with dMAT, adipocytes showed decreased lipolysis and adipokine secretion and increased expression/production of cytokines (IL‐6, G‐CSF) and fibrotic mediators (LOXL2 and the matricellular proteins THSB2 and CTGF). Moreover, some alterations including lipolytic activity and fibro‐inflammation also occurred when the adipocyte/hydrogel culture was mechanically compressed. Notably, CTGF expression levels correlated with the amount of peri‐adipocyte fibrosis in WAT from obese individuals. Moreover, dMAT‐dependent CTGF promoter activity, which depends on β1‐integrin/cytoskeleton pathways, was enhanced in the presence of YAP, a mechanosensitive co‐activator of TEAD transcription factors. Mutation of TEAD binding sites abolished the dMAT‐induced promoter activity. In conclusion, fibrosis may negatively affect human adipocyte function via mechanosensitive molecules, in part stimulated by cell deformation. Published by John Wiley & Sons, Ltd |
|---|---|
| AbstractList | Fibrosis is a hallmark of human white adipose tissue (WAT) during obesity‐induced chronic inflammation. The functional impact of increased interstitial fibrosis (peri‐adipocyte fibrosis) on adjacent adipocytes remains unknown. Here we developed a novel in vitro 3D culture system in which human adipocytes and decellularized material of adipose tissue (dMAT) from obese subjects are embedded in a peptide hydrogel. When cultured with dMAT, adipocytes showed decreased lipolysis and adipokine secretion and increased expression/production of cytokines (IL‐6, G‐CSF) and fibrotic mediators (LOXL2 and the matricellular proteins THSB2 and CTGF). Moreover, some alterations including lipolytic activity and fibro‐inflammation also occurred when the adipocyte/hydrogel culture was mechanically compressed. Notably, CTGF expression levels correlated with the amount of peri‐adipocyte fibrosis in WAT from obese individuals. Moreover, dMAT‐dependent CTGF promoter activity, which depends on β1‐integrin/cytoskeleton pathways, was enhanced in the presence of YAP, a mechanosensitive co‐activator of TEAD transcription factors. Mutation of TEAD binding sites abolished the dMAT‐induced promoter activity. In conclusion, fibrosis may negatively affect human adipocyte function via mechanosensitive molecules, in part stimulated by cell deformation. Published by John Wiley & Sons, Ltd Fibrosis is a hallmark of human white adipose tissue (WAT) during obesity-induced chronic inflammation. The functional impact of increased interstitial fibrosis (peri-adipocyte fibrosis) on adjacent adipocytes remains unknown. Here we developed a novel in vitro 3D culture system in which human adipocytes and decellularized material of adipose tissue (dMAT) from obese subjects are embedded in a peptide hydrogel. When cultured with dMAT, adipocytes showed decreased lipolysis and adipokine secretion and increased expression/production of cytokines (IL-6, G-CSF) and fibrotic mediators (LOXL2 and the matricellular proteins THSB2 and CTGF). Moreover, some alterations including lipolytic activity and fibro-inflammation also occurred when the adipocyte/hydrogel culture was mechanically compressed. Notably, CTGF expression levels correlated with the amount of peri-adipocyte fibrosis in WAT from obese individuals. Moreover, dMAT-dependent CTGF promoter activity, which depends on β1-integrin/cytoskeleton pathways, was enhanced in the presence of YAP, a mechanosensitive co-activator of TEAD transcription factors. Mutation of TEAD binding sites abolished the dMAT-induced promoter activity. In conclusion, fibrosis may negatively affect human adipocyte function via mechanosensitive molecules, in part stimulated by cell deformation. Fibrosis is a hallmark of human white adipose tissue (WAT) during obesity-induced chronic inflammation. The functional impact of increased interstitial fibrosis (peri-adipocyte fibrosis) on adjacent adipocytes remains unknown. Here we developed a novel in vitro 3D culture system in which human adipocytes and decellularized material of adipose tissue (dMAT) from obese subjects are embedded in a peptide hydrogel. When cultured with dMAT, adipocytes showed decreased lipolysis and adipokine secretion and increased expression/production of cytokines (IL-6, G-CSF) and fibrotic mediators (LOXL2 and the matricellular proteins THSB2 and CTGF). Moreover, some alterations including lipolytic activity and fibro-inflammation also occurred when the adipocyte/hydrogel culture was mechanically compressed. Notably, CTGF expression levels correlated with the amount of peri-adipocyte fibrosis in WAT from obese individuals. Moreover, dMAT-dependent CTGF promoter activity, which depends on [beta]1-integrin/cytoskeleton pathways, was enhanced in the presence of YAP, a mechanosensitive co-activator of TEAD transcription factors. Mutation of TEAD binding sites abolished the dMAT-induced promoter activity. In conclusion, fibrosis may negatively affect human adipocyte function via mechanosensitive molecules, in part stimulated by cell deformation. Published by John Wiley & Sons, Ltd [PUBLICATION ABSTRACT] Fibrosis is a hallmark of human white adipose tissue ( WAT ) during obesity‐induced chronic inflammation. The functional impact of increased interstitial fibrosis (peri‐adipocyte fibrosis) on adjacent adipocytes remains unknown. Here we developed a novel in vitro 3D culture system in which human adipocytes and decellularized material of adipose tissue ( dMAT ) from obese subjects are embedded in a peptide hydrogel. When cultured with dMAT , adipocytes showed decreased lipolysis and adipokine secretion and increased expression/production of cytokines ( IL ‐6, G‐ CSF ) and fibrotic mediators ( LOXL2 and the matricellular proteins THSB2 and CTGF ). Moreover, some alterations including lipolytic activity and fibro‐inflammation also occurred when the adipocyte/hydrogel culture was mechanically compressed. Notably, CTGF expression levels correlated with the amount of peri‐adipocyte fibrosis in WAT from obese individuals. Moreover, dMAT ‐dependent CTGF promoter activity, which depends on β 1‐integrin/cytoskeleton pathways, was enhanced in the presence of YAP , a mechanosensitive co‐activator of TEAD transcription factors. Mutation of TEAD binding sites abolished the dMAT ‐induced promoter activity. In conclusion, fibrosis may negatively affect human adipocyte function via mechanosensitive molecules, in part stimulated by cell deformation. Published by John Wiley & Sons, Ltd Fibrosis is a hallmark of human white adipose tissue (WAT) during obesity-induced chronic inflammation. The functional impact of increased interstitial fibrosis (peri-adipocyte fibrosis) on adjacent adipocytes remains unknown. Here we developed a novel in vitro 3D culture system in which human adipocytes and decellularized material of adipose tissue (dMAT) from obese subjects are embedded in a peptide hydrogel. When cultured with dMAT, adipocytes showed decreased lipolysis and adipokine secretion and increased expression/production of cytokines (IL-6, G-CSF) and fibrotic mediators (LOXL2 and the matricellular proteins THSB2 and CTGF). Moreover, some alterations including lipolytic activity and fibro-inflammation also occurred when the adipocyte/hydrogel culture was mechanically compressed. Notably, CTGF expression levels correlated with the amount of peri-adipocyte fibrosis in WAT from obese individuals. Moreover, dMAT-dependent CTGF promoter activity, which depends on β1-integrin/cytoskeleton pathways, was enhanced in the presence of YAP, a mechanosensitive co-activator of TEAD transcription factors. Mutation of TEAD binding sites abolished the dMAT-induced promoter activity. In conclusion, fibrosis may negatively affect human adipocyte function via mechanosensitive molecules, in part stimulated by cell deformation.Fibrosis is a hallmark of human white adipose tissue (WAT) during obesity-induced chronic inflammation. The functional impact of increased interstitial fibrosis (peri-adipocyte fibrosis) on adjacent adipocytes remains unknown. Here we developed a novel in vitro 3D culture system in which human adipocytes and decellularized material of adipose tissue (dMAT) from obese subjects are embedded in a peptide hydrogel. When cultured with dMAT, adipocytes showed decreased lipolysis and adipokine secretion and increased expression/production of cytokines (IL-6, G-CSF) and fibrotic mediators (LOXL2 and the matricellular proteins THSB2 and CTGF). Moreover, some alterations including lipolytic activity and fibro-inflammation also occurred when the adipocyte/hydrogel culture was mechanically compressed. Notably, CTGF expression levels correlated with the amount of peri-adipocyte fibrosis in WAT from obese individuals. Moreover, dMAT-dependent CTGF promoter activity, which depends on β1-integrin/cytoskeleton pathways, was enhanced in the presence of YAP, a mechanosensitive co-activator of TEAD transcription factors. Mutation of TEAD binding sites abolished the dMAT-induced promoter activity. In conclusion, fibrosis may negatively affect human adipocyte function via mechanosensitive molecules, in part stimulated by cell deformation. |
| Author | Clément, K Klein, C du Roure, O Lacasa, M Pellegrinelli, V Lacasa, D Rouault, C Heuvingh, J Clément, E Devulder, A |
| Author_xml | – sequence: 1 givenname: V surname: Pellegrinelli fullname: Pellegrinelli, V email: vp332@medschl.cam.ac.uk organization: INSERM, UMR S 1166, Nutriomics Team, Paris, France – sequence: 2 givenname: J surname: Heuvingh fullname: Heuvingh, J organization: PMMH UMR 7636 CNRS/ESPCI/UPMC, Paris, France – sequence: 3 givenname: O surname: du Roure fullname: du Roure, O organization: PMMH UMR 7636 CNRS/ESPCI/UPMC, Paris, France – sequence: 4 givenname: C surname: Rouault fullname: Rouault, C organization: INSERM, UMR S 1166, Nutriomics Team, Paris, France – sequence: 5 givenname: A surname: Devulder fullname: Devulder, A organization: PMMH UMR 7636 CNRS/ESPCI/UPMC, Paris, France – sequence: 6 givenname: C surname: Klein fullname: Klein, C organization: INSERM, UMR S 1166, Nutriomics Team, Paris, France – sequence: 7 givenname: M surname: Lacasa fullname: Lacasa, M organization: Sorbonne Universités, UPMC University of Paris 06, UMR S 1166, ICAN, Paris, France – sequence: 8 givenname: E surname: Clément fullname: Clément, E organization: PMMH UMR 7636 CNRS/ESPCI/UPMC, Paris, France – sequence: 9 givenname: D surname: Lacasa fullname: Lacasa, D organization: INSERM, UMR S 1166, Nutriomics Team, Paris, France – sequence: 10 givenname: K surname: Clément fullname: Clément, K organization: INSERM, UMR S 1166, Nutriomics Team, Paris, France |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24623048$$D View this record in MEDLINE/PubMed |
| BookMark | eNp90MtKxDAUBuAgio6XhS8gBTe6qJ7cm6WoMyMM6kIR3IQ0TTHam02LztvbMqMLQVdZnO8_J_y7aLOqK4fQIYYzDEDOG9O9nDHK5AaaYFAiVokSm2gyzEhMGZY7aDeEVwBQivNttEOYIBRYMkFy3pemikzmm9ouOxflfWU7X1eRD5EvG2M7l0XpMiqdfTGVt6aIbO_CPtrKTRHcwfrdQ4_T64fLeby4m91cXixiy7iUsRXAgEDGU-asSIkxhDGecZdhSBNFrMot5EYlTCpDgIIEhkESQpzgPLF0D52s9jZt_T7c7XTpg3VFYSpX90FjTrgUghA20ONf9LXu22r43agYpooyMaijterT0mW6aX1p2qX-rmQApytg2zqE1uU_BIMe69Zj3Xqse7Dnv6z1nRnr61rji_8SH75wy79X6_uLh_k6Ea8SPnTu8ydh2jctJJVcP93O9HT2DIvpQukr-gWqtJ1c |
| CitedBy_id | crossref_primary_10_1016_j_cmet_2025_02_004 crossref_primary_10_1002_jbio_201600281 crossref_primary_10_3390_ijms20061462 crossref_primary_10_1007_s10911_018_9420_4 crossref_primary_10_1016_j_tibtech_2024_09_017 crossref_primary_10_1007_s11690_017_0553_1 crossref_primary_10_1172_JCI129192 crossref_primary_10_1096_fj_15_276675 crossref_primary_10_1146_annurev_physiol_060721_092930 crossref_primary_10_1152_ajpendo_00297_2015 crossref_primary_10_1152_ajpregu_00257_2017 crossref_primary_10_1002_adbi_201900286 crossref_primary_10_1210_en_2017_00651 crossref_primary_10_1016_j_jtbi_2019_02_017 crossref_primary_10_1038_srep43787 crossref_primary_10_3389_fendo_2020_00629 crossref_primary_10_1016_j_jtbi_2017_06_030 crossref_primary_10_1038_s41598_021_92732_9 crossref_primary_10_3390_ijms242115508 crossref_primary_10_1016_j_actbio_2018_03_021 crossref_primary_10_1016_j_tem_2015_11_002 crossref_primary_10_1038_s41467_024_54224_y crossref_primary_10_2337_db14_0796 crossref_primary_10_2147_IJN_S278189 crossref_primary_10_1016_j_cmet_2017_01_010 crossref_primary_10_1002_oby_21430 crossref_primary_10_1371_journal_pone_0197777 crossref_primary_10_1002_oby_23734 crossref_primary_10_1016_j_ejcb_2022_151221 crossref_primary_10_1016_j_biotechadv_2015_07_005 crossref_primary_10_1016_j_msec_2021_112313 crossref_primary_10_1007_s12024_015_9661_0 crossref_primary_10_1038_nutd_2015_22 crossref_primary_10_1038_s41598_018_22962_x crossref_primary_10_1038_s41598_020_77498_w crossref_primary_10_1172_jci_insight_122289 crossref_primary_10_3233_BIR_190234 crossref_primary_10_1016_j_cell_2021_12_016 crossref_primary_10_1007_s11095_022_03195_0 crossref_primary_10_1016_S0001_4079_19_30458_3 crossref_primary_10_1038_s41430_021_00914_5 crossref_primary_10_1038_s42255_022_00561_5 crossref_primary_10_2337_db15_1122 crossref_primary_10_1007_s11690_017_0555_z crossref_primary_10_1016_j_cmet_2018_02_005 crossref_primary_10_1016_j_bbalip_2018_05_013 crossref_primary_10_3390_biology13060434 crossref_primary_10_1038_ncb3514 crossref_primary_10_1016_j_celrep_2023_112640 crossref_primary_10_1089_neur_2020_0059 crossref_primary_10_3389_fendo_2022_1080383 crossref_primary_10_3390_cells11152310 crossref_primary_10_1080_21623945_2020_1749500 crossref_primary_10_1002_jbio_202000269 crossref_primary_10_1002_jsp2_1229 crossref_primary_10_1172_jci_insight_154940 crossref_primary_10_3390_cells8121507 crossref_primary_10_1007_s11154_021_09662_0 crossref_primary_10_1007_s00125_016_3933_4 crossref_primary_10_1007_s10753_022_01742_w crossref_primary_10_3390_ijms22052756 crossref_primary_10_1002_advs_202100106 crossref_primary_10_1038_s41419_022_04847_0 crossref_primary_10_1038_s41598_023_31673_x crossref_primary_10_3748_wjg_v25_i15_1797 crossref_primary_10_1111_jvim_16483 crossref_primary_10_1093_asj_sjv170 crossref_primary_10_1038_s41467_018_07453_x crossref_primary_10_1016_j_metabol_2017_10_002 crossref_primary_10_1016_j_actbio_2018_11_048 crossref_primary_10_1136_annrheumdis_2016_210478 crossref_primary_10_20996_1819_6446_2020_02_09 crossref_primary_10_1111_apha_14249 crossref_primary_10_1002_adhm_202300977 crossref_primary_10_4103_JMU_JMU_85_20 crossref_primary_10_1002_jcb_30351 crossref_primary_10_1007_s12079_018_0458_2 crossref_primary_10_1507_endocrj_EJ22_0035 crossref_primary_10_3390_genes11060600 crossref_primary_10_1016_j_bbalip_2024_159470 crossref_primary_10_3390_cancers14215402 crossref_primary_10_1002_ctm2_543 crossref_primary_10_1038_s43856_025_00774_1 crossref_primary_10_1038_s41467_022_33800_0 crossref_primary_10_3390_biom14101223 crossref_primary_10_1080_21623945_2023_2268261 crossref_primary_10_1097_QAD_0000000000002168 crossref_primary_10_3390_cells9010151 crossref_primary_10_1007_s00418_022_02091_3 crossref_primary_10_34133_2021_1412542 crossref_primary_10_1051_medsci_20183405015 crossref_primary_10_1083_jcb_201409063 crossref_primary_10_1002_jcp_31008 crossref_primary_10_3390_cells12222599 crossref_primary_10_1016_j_mad_2021_111522 crossref_primary_10_1111_jocd_16679 crossref_primary_10_1111_cas_15940 crossref_primary_10_1007_s12020_016_1089_0 crossref_primary_10_1080_21623945_2019_1612223 crossref_primary_10_3390_ijms24119276 crossref_primary_10_1038_s41574_024_01071_y crossref_primary_10_1210_jc_2017_00138 |
| Cites_doi | 10.1210/en.2006-0386 10.1111/j.1478-3231.2008.01826.x 10.1210/me.2008-0183 10.1074/jbc.M600214200 10.1152/ajpendo.00329.2010 10.1038/nrm2594 10.1161/01.ATV.18.6.894 10.1158/0008-5472.CAN-08-2997 10.1152/japplphysiol.90584.2008 10.1038/ncb2756 10.1172/JCI45887 10.1210/jc.2013-3253 10.1111/j.1467-789X.2010.00811.x 10.1128/MCB.01300-08 10.1242/jcs.093005 10.1101/gad.1664408 10.1152/ajpcell.00328.2012 10.2337/db10-0585 10.1002/art.24620 10.1128/MCB.00192-09 10.1080/08977190802025602 10.1128/MCB.22.16.5912-5922.2002 10.1016/j.cell.2009.10.027 10.1096/fj.05-5424rev 10.1152/ajpcell.00333.2007 10.1016/j.ceb.2006.08.009 10.1186/gb-2008-9-1-r14 10.1038/nrm2122 10.2337/diabetes.54.8.2277 10.1016/j.cell.2006.02.050 10.1055/s-2003-39070 10.1152/ajpendo.2000.278.6.E1144 10.1210/jc.2009-0947 10.1186/1755-1536-5-S1-S24 10.1152/physiolgenomics.90291.2008 10.1089/tea.2007.0143 10.1159/000262316 10.1038/nrm3416 |
| ContentType | Journal Article |
| Copyright | Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| Copyright_xml | – notice: Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd – notice: Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| DBID | BSCLL AAYXX CITATION CGR CUY CVF ECM EIF NPM 7QP 7QR 7T5 7TK 7TM 7TO 8FD FR3 H94 K9. P64 RC3 7X8 |
| DOI | 10.1002/path.4347 |
| DatabaseName | Istex CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Calcium & Calcified Tissue Abstracts Chemoreception Abstracts Immunology Abstracts Neurosciences Abstracts Nucleic Acids Abstracts Oncogenes and Growth Factors Abstracts Technology Research Database Engineering Research Database AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) Biotechnology and BioEngineering Abstracts Genetics Abstracts MEDLINE - Academic |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Genetics Abstracts Oncogenes and Growth Factors Abstracts Technology Research Database Nucleic Acids Abstracts AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) Chemoreception Abstracts Immunology Abstracts Engineering Research Database Calcium & Calcified Tissue Abstracts Neurosciences Abstracts Biotechnology and BioEngineering Abstracts MEDLINE - Academic |
| DatabaseTitleList | MEDLINE Genetics Abstracts CrossRef MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1096-9896 |
| EndPage | 195 |
| ExternalDocumentID | 3302211311 24623048 10_1002_path_4347 PATH4347 ark_67375_WNG_FGZ0LFL9_D |
| Genre | article Research Support, Non-U.S. Gov't Journal Article |
| GroupedDBID | --- -~X .3N .55 .GA .GJ .Y3 05W 0R~ 10A 123 1KJ 1L6 1OB 1OC 1ZS 29L 31~ 33P 3O- 3SF 3UE 3WU 4.4 4ZD 50Y 50Z 51W 51X 52M 52N 52O 52P 52R 52S 52T 52U 52V 52W 52X 53G 5RE 5VS 66C 702 7PT 8-0 8-1 8-3 8-4 8-5 8UM 930 A01 A03 AAESR AAEVG AAHHS AANLZ AAONW AASGY AAXRX AAZKR ABCQN ABCUV ABEML ABIJN ABJNI ABLJU ABQWH ABXGK ACAHQ ACBWZ ACCFJ ACCZN ACFBH ACGFS ACGOF ACIWK ACMXC ACPOU ACPRK ACSCC ACXBN ACXQS ADBBV ADBTR ADEOM ADIZJ ADKYN ADMGS ADOZA ADXAS ADZMN AEEZP AEIGN AEIMD AENEX AEQDE AEUQT AEUYR AFBPY AFFNX AFFPM AFGKR AFPWT AFRAH AFZJQ AHBTC AHMBA AI. AIACR AITYG AIURR AIWBW AJBDE ALAGY ALMA_UNASSIGNED_HOLDINGS ALUQN AMBMR AMYDB ASPBG ATUGU AVWKF AZBYB AZFZN AZVAB BAFTC BDRZF BFHJK BHBCM BMXJE BROTX BRXPI BSCLL BY8 C45 CS3 D-6 D-7 D-E D-F DCZOG DPXWK DR2 DRFUL DRMAN DRSTM DU5 EBS EJD EMOBN F00 F01 F04 F5P FEDTE FUBAC G-S G.N GNP GODZA GSXLS H.X HBH HF~ HGLYW HHY HHZ HVGLF HZ~ IX1 J0M J5H JPC KBYEO KQQ L7B LATKE LAW LC2 LC3 LEEKS LH4 LITHE LOXES LP6 LP7 LUTES LW6 LYRES M68 MEWTI MK4 MRFUL MRMAN MRSTM MSFUL MSMAN MSSTM MVM MXFUL MXMAN MXSTM N04 N05 N9A NF~ NNB O66 O9- OHT OIG OVD P2P P2W P2X P2Z P4B P4D PALCI PQQKQ Q.N Q11 QB0 QRW R.K RIWAO RJQFR ROL RWI RX1 SAMSI SUPJJ SV3 TEORI UB1 V2E VH1 W8V W99 WBKPD WH7 WHWMO WIB WIH WIJ WIK WJL WOHZO WQJ WRC WUP WVDHM WXI WXSBR X7M XG1 XPP XV2 YQI YQJ ZGI ZXP ZZTAW ~IA ~KM ~WT AAHQN AAIPD AAMNL AANHP AAYCA ACRPL ACYXJ ADNMO AFWVQ ALVPJ AAYXX AEYWJ AGHNM AGQPQ AGYGG CITATION CGR CUY CVF ECM EIF NPM 7QP 7QR 7T5 7TK 7TM 7TO 8FD AAMMB AEFGJ AGXDD AIDQK AIDYY FR3 H94 K9. P64 RC3 7X8 |
| ID | FETCH-LOGICAL-c4577-c604020d5b4ec6b2aa2445d5ed10b892c9fc0fa98479a2030704107222e6558c3 |
| IEDL.DBID | DR2 |
| ISSN | 0022-3417 1096-9896 |
| IngestDate | Fri Jul 11 12:09:30 EDT 2025 Fri Jul 25 12:28:14 EDT 2025 Thu Apr 03 07:01:44 EDT 2025 Tue Jul 01 04:21:12 EDT 2025 Thu Apr 24 23:08:22 EDT 2025 Wed Jan 22 16:28:08 EST 2025 Wed Oct 30 09:51:08 EDT 2024 |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 2 |
| Keywords | fibrosis human obesity 3D culture adipocytes |
| Language | English |
| License | Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c4577-c604020d5b4ec6b2aa2445d5ed10b892c9fc0fa98479a2030704107222e6558c3 |
| Notes | ark:/67375/WNG-FGZ0LFL9-D istex:71322AEA4B9537AB986FE4418EDE5B44399A83E3 ArticleID:PATH4347 Appendix S1. Supplementary materialFrom WAT extracellular matrix to dMAT. (A) Photomicrographs from OCT imaging of non-digested material of adipose tissue (MAT) obtained from subcutaneous adipose tissue (SAT) sample of obese subject before (left photomicrograph) and after (right photomicrographs) the decellularization process. During this process, adipocytes (*) surrounded by collagen fibres, and other cells composing WAT are eliminated without alterations of the collagen fibre structure. Scale bars = 500 µm and 100 µm. (B) Observation of dMAT by immunofluorescence analysis using antibodies directed against type I, III collagen (red, Cy3-conjugated anti-rabbit IgG) and type VI collagen (green, Cy2-conjugated anti-mouse IgG) (scale bar = 100 µm) and second harmonic generation, SHG (scale bar = 50 µm). (C) Observation of obese SAT by immunofluorescence analysis. Diversity of collagens were determined using antibodies directed against type I, III, IV collagen (green, Cy2-conjugated anti-rabbit IgG), type V, type VI, XVIII collagen (red, Cy3-conjugated anti-mouse IgG) and FN (green, Cy2-conjugated anti-mouse IgG). Nuclei were stained with DAPI. Scale bar = 100 µm. (D) Observation of fibrotic depots extracted from obese SAT by OCT imaging and immunofluorescence microscopy using antibodies directed against type I (red, Cy3-conjugated anti-rabbit IgG) and type VI collagen (green, Cy2-conjugated anti-mouse IgG). The BMI of the obese subject was 48; age 46 years3D culture of human unilocular adipocytes, tissue microstructure and maintenance of viable mature adipocytes. (A) Experimental procedure of human mature adipocyte culture in the 3D hydrogel. Mature adipocytes were isolated from SAT of lean subjects and embedded in the peptidic hydrogel. The photograph shows floating hydrogel, containing unilocular adipocytes in culture media. (B) Comparison of insulin response between floating adipocytes (2D) and adipocytes cultured for 24 h into the hydrogel (3D). Insulin response was evaluated by insulin (10 nm) stimulation of serine473 phosphorylation of Akt (pS473Akt) for 10 min. A representative western blot is presented among three separate experiments. (C) Comparison of LDH activity (cytotoxicity), lipolytic activity (glycerol release) and leptin secretion between 24 h floating adipocytes (2D, white bars) and adipocytes cultured for 24 h into the hydrogel (3D, black bars). Data are mean ± SEM of five separate experiments from lean SAT. **p < 0.01, ***p < 0.001, 2D adipocytes versus 3D adipocytes. (D) Metabolic and secretory functions of human adipocytes from lean SAT were followed for 7 days (d) in the 3D setting. Lipolytic activity was evaluated by glycerol release after isoproterenol stimulation (1 μm) for 4 h. Leptin secretion was measured by ELISA assay. Data are mean ± SEM of six separate experiments. AU, arbitrary unitsAnalysis of adipocyte flattening in culture with obese dMAT. (A) Observation of a 100 µm section of the hydrogel by OCT imaging containing unilocular adipocytes from lean SAT with dMAT. The transverse view (higher panel) shows organization of collagen fibres in the 3D setting. Scale bar = 50 µm. Adipocytes were reconstructed in 3D to appreciate dMAT-induced changes in the adipocyte morphology (lower panel). A representative 3D adipocyte reconstruction is presented among 26 analyses. (B) Histogram of the flattening measured in two dimensions for adipocytes in 3D culture without dMAT (blue bars) and with dMAT (red bars) (n > 500 adipocytes)Lipolytic activity of adipocytes cultured with obese dMAT in the 3D hydrogel. (A) Representative experiment of dose-dependent effects of dMAT on glycerol release in basal (white line) and stimulated conditions, isoproterenol (1 μm) (black line, Iso) from lean adipocytes cultured for 3 days in the 3D setting, corresponding to a representative experiment of three independent experiments (R2= 0.9267, basal conditions, and R2 = 0.9064, β-adrenergic stimulated conditions). *p < 0.05. (B) Dose-dependent effects of dMAT on adipocyte cytotoxicity corresponding to a representative experiment of three independent experiments. Adipocyte cytotoxycity was evaluated by LDH activity after 3 days in the 3D culture model. The SAT of lean subjects (mean BMI = 23.05 ± 0.38 kg/m2) was used to prepare adipocytes and SAT of obese subjects (mean BMI = 45.2 ± 1.5 kg/m2) to prepare dMATMetabolic and secretory functions of adipocytes submitted to mechanical deformation and cultured with obese dMAT in the 3D hydrogel. (A) Scheme of the set-up used to apply controlled deformation in a multi-well plate. The set-up allows the application of increasing deformation in the one direction of the plate, whereas the other direction is used to test reproducibility. (B-D) Effects of the mechanical constraints on adipocyte cytotoxicity (B) and secretion of leptin (C) and adiponectin (D), which were evaluated for each deformation from 0% to 50%. Adipocyte cytotoxycity was evaluated by LDH activity and the leptin and adiponectin secretions were measured using an ELISA after 3 days in the 3D setting. Data are presented as mean ± SEM of five independent experiments. NS, not significant. (E) The heat map with graded shades from green to red represents the secretion level (significant levels > 10 pg/ml) of 14 cytokines and chemokines screened by Multiplex analysis. Brace identifies the seven showing the highest secretion level. (F) Significant changes in the secretions of inflammatory molecules (IL-6 and G-CSF) by adipocytes in the 3D setting with dMAT (AD + dMAT, black bars) submitted to a mechanical deformation (50%, AD + DEF, grey bars) or cultured with dMAT under mechanical deformation (AD + dMAT + DEF, dark grey bars), compared to adipocytes cultured alone (control AD, white bars). The results are presented as the fold differences over the control. Data are presented as mean ± SEM of three independent experiments. *p < 0.05, AD versus AD + dMAT or AD + DEF or AD + dMAT + DEF. The SAT of lean subjects (mean BMI = 23.05 ± 0.38 kg/m2) was used to prepare adipocytes and SAT of obese subjects (mean BMI = 45.2 ± 1.5 kg/m2) to prepare dMATMetabolic and secretory functions of adipocytes cultured with dMAT from SAT of lean subjects (BMI 22.6 ± 0.7, n = 12) in the 3D setting. (A) ELISA analysis of the secretion of leptin, adiponectin and IL-6 by adipocytes cultured alone (AD, white bars) or with dMAT prepared from SAT of lean subjects (0.05 mg/ml, AD + dMAT, black bars) in the 3D setting. (B) Lipolytic activity was evaluated by the glycerol release from either adipocytes cultured alone (AD) or with dMAT prepared from SAT of lean subjects (0.05 mg/ml, AD + dMAT) in the 3D setting. Glycerol release was measured in the basal (white bars) or stimulated conditions (isoproterenol, 1 μm; black bars, Iso) for 4 h. Data are presented as mean ± SEM of four independent experiments. ns, not significant. The SAT of lean subjects was used to prepare adipocytes and dMAT (mean BMI = 23.05 ± 0.38 kg/m2 and mean BMI = 22.6 ± 0.7 kg/m2, respectively)Role of β1-integrin in mediating alterations of adipocytes induced by obese dMAT. ELISA analysis of leptin and adiponectin secretion by adipocytes in the 3D setting with dMAT (AD + dMAT, black bars) compared to either adipocytes cultured alone (control AD, white bars). Adipocytes were treated with IgG1 or β1-integrin neutralizing antibody (ab β1-int). Data are presented as mean ± SEM of five independent experiments. *p < 0.05, AD versus AD + dMAT, ns, not significant. The SAT of lean subjects (mean BMI = 23.05 ± 0.38 kg/m2) was used to prepare adipocytes and SAT of obese subjects (mean BMI = 45.2 ± 1.5 kg/m2) to prepare dMATEffect of obese dMAT on kinase phosphorylation profile, actin cytoskeleton remodelling and gene expression. (A) Cell lysates prepared from four independent experiments of adipocytes cultured for 30 min in the 3D hydrogel alone (control, AD) or exposed to dMAT (AD + dMAT) or 50% mechanical deformation (AD + DEF) were pooled and analysed for the phosphorylation of different kinases using the Human Phospho-Kinase Antibody Array Kit, as described in Materials and methods: (1) TOR; (2) Src; (3) Hck; (4) EGFR; (5) CREB; (6) Lyn; (7) Yes; (8) Chk-2; (9) PRAS-40; (10) ERK 1/2; (11) MSK 1/2; (12) HSP27; (13) FAK; (14) AMPKα2; (15) STAT2; (16) STAT6; (17) GSK-3α/β; (18) AKT (S473); (19) STAT5a; (20) STAT5b; (21) STAT5a/b; (22) AKT (T308); (23) P70 S6K (T389); (24) p70 S6K (T421/S424); (25) STAT3; (26) HSP60; (27) P53 (S46); (28) p53 (S15); (29) RSK 1/2/3; (30) c-jun. PC, positive control; NC, negative control. (B) Human preadipocytes isolated from SAT of lean subjects (BMI: 24 kg/m2) were differentiated in the 3D hydrogel for 7 days with (dMAT) or without dMAT (control) and examined by confocal microscopy for actin staining (red, phalloidin-AlexaFluor 546); scale bar = 50 µm. (C) A heat map representation of the mRNA expression of several genes involved in metabolism, ER stress, inflammation and ECM remodelling, as quantified using real-time PCR and normalized to 18S in adipocytes cultured alone (control AD) or with dMAT in the 3D culture model (AD + dMAT). Graded shades from green to red represent the fold differences between the control adipocytes and AD + dMAT. Data are presented as mean ± SEM of six independent experiments. #, mechanosensitive genes. (D) LOX gene expressions was quantified by real-time PCR and normalized to 18S in adipocytes isolated from SAT of lean subjects. Results are expressed as fold differences between adipocytes cultured in the 3D hydrogel for 3 days alone (AD, white bar), with dMAT (AD + dMAT, black bar) or submitted to compression (AD + DEF, grey bar). Data are represented as mean ± SEM of five separate experiments. ns, non significant. The SAT of lean subjects (mean BMI = 23.05 ± 0.38 kg/m2) was used to prepare adipocytes and SAT of obese subjects (mean BMI = 45 No conflicts of interest were declared. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| PMID | 24623048 |
| PQID | 1524139346 |
| PQPubID | 1006392 |
| PageCount | 13 |
| ParticipantIDs | proquest_miscellaneous_1525766224 proquest_journals_1524139346 pubmed_primary_24623048 crossref_primary_10_1002_path_4347 crossref_citationtrail_10_1002_path_4347 wiley_primary_10_1002_path_4347_PATH4347 istex_primary_ark_67375_WNG_FGZ0LFL9_D |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | June 2014 |
| PublicationDateYYYYMMDD | 2014-06-01 |
| PublicationDate_xml | – month: 06 year: 2014 text: June 2014 |
| PublicationDecade | 2010 |
| PublicationPlace | Chichester, UK |
| PublicationPlace_xml | – name: Chichester, UK – name: England – name: Bognor Regis |
| PublicationTitle | The Journal of pathology |
| PublicationTitleAlternate | J. Pathol |
| PublicationYear | 2014 |
| Publisher | John Wiley & Sons, Ltd Wiley Subscription Services, Inc |
| Publisher_xml | – name: John Wiley & Sons, Ltd – name: Wiley Subscription Services, Inc |
| References | Pasarica M, Gowronska-Kozak B, Burk D, et al. Adipose tissue collagen VI in obesity. J Clin Endocrinol Metab 2009; 94: 5155-5162. Phanish MK, Winn SK, Dockrell MEC. Connective tissue growth factor (CTGF, CCN2) - a marker, mediator and therapeutic target for renal fibrosis. Nephron Exp Nephrol 2010; 114: e83-92. Ingber DE. Cellular mechanotransduction: putting all the pieces together again. FASEB J Off Publ Fed Am Soc Exp Biol 2006; 20: 811-827. Ponticos M, Holmes AM, Shi-wen X, et al. Pivotal role of connective tissue growth factor in lung fibrosis: MAPK-dependent transcriptional activation of type I collagen. Arthritis Rheum 2009; 60: 2142-2155. Zhao B, Kim J, Ye X, et al. Both TEAD-binding and WW domains are required for the growth stimulation and oncogenic transformation activity of yes-associated protein. Cancer Res 2009; 69: 1089-1098. Wang S, Nagrath D, Chen PC, et al. Three-dimensional primary hepatocyte culture in synthetic self-assembling peptide hydrogel. Tissue Eng A 2008; 14: 227-236. Khan T, Muise ES, Iyengar P, et al. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol Cell Biol 2009; 29: 1575-1591. Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest 2011; 121: 2094-2101. Cancello R, Henegar C, Viguerie N, et al. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 2005; 54: 2277-2286. Divoux A, Tordjman J, Lacasa D, et al. Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes 2010; 59: 2817-2825. Halder G, Dupont S, Piccolo S. Transduction of mechanical and cytoskeletal cues by YAP and TAZ. Nat Rev Mol Cell Biol 2012; 13: 591-600. De Winter P, Leoni P, Abraham D. Connective tissue growth factor: structure-function relationships of a mosaic, multifunctional protein. Growth Factors Chur 2008; 26: 80-91. Chun TH, Hotary KB, Sabeh F, et al. A pericellular collagenase directs the three-dimensional development of white adipose tissue. Cell 2006; 125: 577-591. Lipson KE, Wong C, Teng Y, et al. CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis. Fibrogen Tissue Repair 2012; 5(suppl 1): S24. Divoux A, Clément K. Architecture and the extracellular matrix: the still unappreciated components of the adipose tissue. Obes Rev Off J Int Assoc Study Obes 2011; 12: e494-503. Gressner OA, Gressner AM. Connective tissue growth factor: a fibrogenic master switch in fibrotic liver diseases. Liver Int Off J Int Assoc Study Liver 2008; 28: 1065-1079. Halberg N, Khan T, Trujillo ME, et al. Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue. Mol Cell Biol 2009 ; 29: 4467-4483. Calvo F, Ege N, Grande-Garcia A, et al. Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat Cell Biol 2013; 15: 637-646. Henegar C, Tordjman J, Achard V, et al. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol 2008; 9: R14. Zeisberg M, Kalluri R. Cellular mechanisms of tissue fibrosis. 1. Common and organ-specific mechanisms associated with tissue fibrosis. Am J Physiol Cell Physiol 2013; 304: C216-225. Wang N, Tytell JD, Ingber DE. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol 2009; 10: 75-82. Mammoto A, Mammoto T, Ingber DE. Mechanosensitive mechanisms in transcriptional regulation. J Cell Sci 2012; 125: 3061-3073. Keophiphath M, Achard V, Henegar C, et al. Macrophage-secreted factors promote a profibrotic phenotype in human preadipocytes. Mol Endocrinol 2009; 23: 11-24. Levental KR, Yu H, Kass L, et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 2009; 139: 891-906. Taleb S, Cancello R, et al. Cathepsin s promotes human preadipocyte differentiation: possible involvement of fibronectin degradation. Endocrinology 2006; 147: 4950-4959. Tan JTM, McLennan SV, Song WW, et al. Connective tissue growth factor inhibits adipocyte differentiation. Am J Physiol Cell Physiol 2008; 295: C740-751. Peterson JM, Pizza FX. Cytokines derived from cultured skeletal muscle cells after mechanical strain promote neutrophil chemotaxis in vitro. J Appl Physiol (Bethesda, MD, 1985) 2009; 106: 130-137. Spencer M, Yao-Borengasser A, Unal R, et al. Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activation. Am J Physiol Endocrinol Metab 2010; 299: E1016-1027. Larsen M, Artym VV, et al. The matrix reorganized: extracellular matrix remodeling and integrin signaling. Curr Opin Cell Biol 2006; 18: 463-471. Parton RG, Simons K. The multiple faces of caveolae. Nat Rev Mol Cell Biol 2007; 8: 185-194. Abdennour M, Reggio S, Le Naour G, et al. Association of adipose tissue and liver fibrosis with tissue stiffness in morbid obesity: links with diabetes and BMI loss after gastric bypass. J Clin Endocrinol Metab 2014; jc20133253. Horowitz JF, Klein S. Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women. Am J Physiol Endocrinol Metab 2000; 278: E1144-1152. Zhao B, Ye X, Yu J, et al. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev 2008; 22: 1962-1971. Chaqour B, Yang R, Sha Q. Mechanical stretch modulates the promoter activity of the profibrotic factor CCN2 through increased actin polymerization and NF-κB activation. J Biol Chem 2006; 281: 20608-20622. Klein S, de Fougerolles AR, Blaikie P, et al. α5β1 integrin activates an NF-κB-dependent program of gene expression important for angiogenesis and inflammation. Mol Cell Biol 2002; 22: 5912-5922. Yang R, Amir J, Liu H, Chaqour B. Mechanical strain activates a program of genes functionally involved in paracrine signaling of angiogenesis. Physiol Genom 2008; 36: 1-14. Okada M, Matsumori A, Ono K, et al. Cyclic stretch upregulates production of interleukin-8 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in human endothelial cells. Arterioscler Thromb Vasc Biol 1998; 18: 894-901. Gesta S, Lolmède K, Daviaud D, et al. Culture of human adipose tissue explants leads to profound alteration of adipocyte gene expression. Horm Metab Res 2003; 35: 158-163. 2009; 23 2009; 69 2010; 59 2000; 278 2009; 60 2013; 304 2008; 9 2003; 35 2008; 14 2008; 36 2006; 18 2011; 12 2012; 125 2012; 13 2009; 29 2009; 139 1998; 18 2013; 15 2006; 20 2009; 10 2009; 94 2010; 114 2010; 299 2008; 28 2002; 22 2007; 8 2008; 26 2005; 54 2008; 22 2014 2006; 281 2012; 5 2008; 295 2011; 121 2006; 125 2006; 147 2009; 106 e_1_2_8_28_1 e_1_2_8_29_1 e_1_2_8_24_1 e_1_2_8_25_1 e_1_2_8_26_1 e_1_2_8_27_1 e_1_2_8_3_1 e_1_2_8_2_1 e_1_2_8_5_1 e_1_2_8_4_1 e_1_2_8_7_1 e_1_2_8_6_1 e_1_2_8_9_1 e_1_2_8_8_1 e_1_2_8_20_1 e_1_2_8_21_1 e_1_2_8_22_1 e_1_2_8_23_1 e_1_2_8_40_1 e_1_2_8_17_1 e_1_2_8_18_1 e_1_2_8_39_1 e_1_2_8_19_1 e_1_2_8_13_1 e_1_2_8_36_1 e_1_2_8_14_1 e_1_2_8_35_1 e_1_2_8_15_1 e_1_2_8_38_1 e_1_2_8_16_1 e_1_2_8_37_1 e_1_2_8_32_1 e_1_2_8_10_1 e_1_2_8_31_1 e_1_2_8_11_1 e_1_2_8_34_1 e_1_2_8_12_1 e_1_2_8_33_1 e_1_2_8_30_1 |
| References_xml | – reference: Khan T, Muise ES, Iyengar P, et al. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol Cell Biol 2009; 29: 1575-1591. – reference: Parton RG, Simons K. The multiple faces of caveolae. Nat Rev Mol Cell Biol 2007; 8: 185-194. – reference: De Winter P, Leoni P, Abraham D. Connective tissue growth factor: structure-function relationships of a mosaic, multifunctional protein. Growth Factors Chur 2008; 26: 80-91. – reference: Zhao B, Ye X, Yu J, et al. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev 2008; 22: 1962-1971. – reference: Yang R, Amir J, Liu H, Chaqour B. Mechanical strain activates a program of genes functionally involved in paracrine signaling of angiogenesis. Physiol Genom 2008; 36: 1-14. – reference: Levental KR, Yu H, Kass L, et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 2009; 139: 891-906. – reference: Ponticos M, Holmes AM, Shi-wen X, et al. Pivotal role of connective tissue growth factor in lung fibrosis: MAPK-dependent transcriptional activation of type I collagen. Arthritis Rheum 2009; 60: 2142-2155. – reference: Lipson KE, Wong C, Teng Y, et al. CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis. Fibrogen Tissue Repair 2012; 5(suppl 1): S24. – reference: Mammoto A, Mammoto T, Ingber DE. Mechanosensitive mechanisms in transcriptional regulation. J Cell Sci 2012; 125: 3061-3073. – reference: Okada M, Matsumori A, Ono K, et al. Cyclic stretch upregulates production of interleukin-8 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in human endothelial cells. Arterioscler Thromb Vasc Biol 1998; 18: 894-901. – reference: Zhao B, Kim J, Ye X, et al. Both TEAD-binding and WW domains are required for the growth stimulation and oncogenic transformation activity of yes-associated protein. Cancer Res 2009; 69: 1089-1098. – reference: Zeisberg M, Kalluri R. Cellular mechanisms of tissue fibrosis. 1. Common and organ-specific mechanisms associated with tissue fibrosis. Am J Physiol Cell Physiol 2013; 304: C216-225. – reference: Klein S, de Fougerolles AR, Blaikie P, et al. α5β1 integrin activates an NF-κB-dependent program of gene expression important for angiogenesis and inflammation. Mol Cell Biol 2002; 22: 5912-5922. – reference: Horowitz JF, Klein S. Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women. Am J Physiol Endocrinol Metab 2000; 278: E1144-1152. – reference: Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest 2011; 121: 2094-2101. – reference: Gressner OA, Gressner AM. Connective tissue growth factor: a fibrogenic master switch in fibrotic liver diseases. Liver Int Off J Int Assoc Study Liver 2008; 28: 1065-1079. – reference: Tan JTM, McLennan SV, Song WW, et al. Connective tissue growth factor inhibits adipocyte differentiation. Am J Physiol Cell Physiol 2008; 295: C740-751. – reference: Divoux A, Tordjman J, Lacasa D, et al. Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes 2010; 59: 2817-2825. – reference: Larsen M, Artym VV, et al. The matrix reorganized: extracellular matrix remodeling and integrin signaling. Curr Opin Cell Biol 2006; 18: 463-471. – reference: Pasarica M, Gowronska-Kozak B, Burk D, et al. Adipose tissue collagen VI in obesity. J Clin Endocrinol Metab 2009; 94: 5155-5162. – reference: Cancello R, Henegar C, Viguerie N, et al. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 2005; 54: 2277-2286. – reference: Abdennour M, Reggio S, Le Naour G, et al. Association of adipose tissue and liver fibrosis with tissue stiffness in morbid obesity: links with diabetes and BMI loss after gastric bypass. J Clin Endocrinol Metab 2014; jc20133253. – reference: Keophiphath M, Achard V, Henegar C, et al. Macrophage-secreted factors promote a profibrotic phenotype in human preadipocytes. Mol Endocrinol 2009; 23: 11-24. – reference: Phanish MK, Winn SK, Dockrell MEC. Connective tissue growth factor (CTGF, CCN2) - a marker, mediator and therapeutic target for renal fibrosis. Nephron Exp Nephrol 2010; 114: e83-92. – reference: Spencer M, Yao-Borengasser A, Unal R, et al. Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activation. Am J Physiol Endocrinol Metab 2010; 299: E1016-1027. – reference: Halberg N, Khan T, Trujillo ME, et al. Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue. Mol Cell Biol 2009 ; 29: 4467-4483. – reference: Chun TH, Hotary KB, Sabeh F, et al. A pericellular collagenase directs the three-dimensional development of white adipose tissue. Cell 2006; 125: 577-591. – reference: Henegar C, Tordjman J, Achard V, et al. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol 2008; 9: R14. – reference: Ingber DE. Cellular mechanotransduction: putting all the pieces together again. FASEB J Off Publ Fed Am Soc Exp Biol 2006; 20: 811-827. – reference: Halder G, Dupont S, Piccolo S. Transduction of mechanical and cytoskeletal cues by YAP and TAZ. Nat Rev Mol Cell Biol 2012; 13: 591-600. – reference: Chaqour B, Yang R, Sha Q. Mechanical stretch modulates the promoter activity of the profibrotic factor CCN2 through increased actin polymerization and NF-κB activation. J Biol Chem 2006; 281: 20608-20622. – reference: Calvo F, Ege N, Grande-Garcia A, et al. Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat Cell Biol 2013; 15: 637-646. – reference: Taleb S, Cancello R, et al. Cathepsin s promotes human preadipocyte differentiation: possible involvement of fibronectin degradation. Endocrinology 2006; 147: 4950-4959. – reference: Wang S, Nagrath D, Chen PC, et al. Three-dimensional primary hepatocyte culture in synthetic self-assembling peptide hydrogel. Tissue Eng A 2008; 14: 227-236. – reference: Wang N, Tytell JD, Ingber DE. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol 2009; 10: 75-82. – reference: Peterson JM, Pizza FX. Cytokines derived from cultured skeletal muscle cells after mechanical strain promote neutrophil chemotaxis in vitro. J Appl Physiol (Bethesda, MD, 1985) 2009; 106: 130-137. – reference: Gesta S, Lolmède K, Daviaud D, et al. Culture of human adipose tissue explants leads to profound alteration of adipocyte gene expression. Horm Metab Res 2003; 35: 158-163. – reference: Divoux A, Clément K. Architecture and the extracellular matrix: the still unappreciated components of the adipose tissue. Obes Rev Off J Int Assoc Study Obes 2011; 12: e494-503. – volume: 69 start-page: 1089 year: 2009 end-page: 1098 article-title: Both TEAD‐binding and WW domains are required for the growth stimulation and oncogenic transformation activity of yes‐associated protein publication-title: Cancer Res – volume: 36 start-page: 1 year: 2008 end-page: 14 article-title: Mechanical strain activates a program of genes functionally involved in paracrine signaling of angiogenesis publication-title: Physiol Genom – volume: 22 start-page: 1962 year: 2008 end-page: 1971 article-title: TEAD mediates YAP‐dependent gene induction and growth control publication-title: Genes Dev – volume: 29 start-page: 4467 year: 2009 end-page: 4483 article-title: Hypoxia‐inducible factor 1 induces fibrosis and insulin resistance in white adipose tissue publication-title: Mol Cell Biol – volume: 5 start-page: S24 issue: suppl 1 year: 2012 article-title: CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis publication-title: Fibrogen Tissue Repair – volume: 8 start-page: 185 year: 2007 end-page: 194 article-title: The multiple faces of caveolae publication-title: Nat Rev Mol Cell Biol – volume: 9 start-page: R14 year: 2008 article-title: Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity publication-title: Genome Biol – volume: 54 start-page: 2277 year: 2005 end-page: 2286 article-title: Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery‐induced weight loss publication-title: Diabetes – volume: 29 start-page: 1575 year: 2009 end-page: 1591 article-title: Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI publication-title: Mol Cell Biol – volume: 13 start-page: 591 year: 2012 end-page: 600 article-title: Transduction of mechanical and cytoskeletal cues by YAP and TAZ publication-title: Nat Rev Mol Cell Biol – volume: 139 start-page: 891 year: 2009 end-page: 906 article-title: Matrix crosslinking forces tumor progression by enhancing integrin signaling publication-title: Cell – volume: 299 start-page: E1016 year: 2010 end-page: 1027 article-title: Adipose tissue macrophages in insulin‐resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activation publication-title: Am J Physiol Endocrinol Metab – volume: 125 start-page: 577 year: 2006 end-page: 591 article-title: A pericellular collagenase directs the three‐dimensional development of white adipose tissue publication-title: Cell – volume: 18 start-page: 894 year: 1998 end-page: 901 article-title: Cyclic stretch upregulates production of interleukin‐8 and monocyte chemotactic and activating factor/monocyte chemoattractant protein‐1 in human endothelial cells publication-title: Arterioscler Thromb Vasc Biol – volume: 15 start-page: 637 year: 2013 end-page: 646 article-title: Mechanotransduction and YAP‐dependent matrix remodelling is required for the generation and maintenance of cancer‐associated fibroblasts publication-title: Nat Cell Biol – volume: 114 start-page: e83 year: 2010 end-page: 92 article-title: Connective tissue growth factor (CTGF, CCN2) – a marker, mediator and therapeutic target for renal fibrosis publication-title: Nephron Exp Nephrol – volume: 60 start-page: 2142 year: 2009 end-page: 2155 article-title: Pivotal role of connective tissue growth factor in lung fibrosis: MAPK‐dependent transcriptional activation of type I collagen publication-title: Arthritis Rheum – volume: 304 start-page: C216 year: 2013 end-page: 225 article-title: Cellular mechanisms of tissue fibrosis. 1. Common and organ‐specific mechanisms associated with tissue fibrosis publication-title: Am J Physiol Cell Physiol – volume: 28 start-page: 1065 year: 2008 end-page: 1079 article-title: Connective tissue growth factor: a fibrogenic master switch in fibrotic liver diseases publication-title: Liver Int Off J Int Assoc Study Liver – volume: 18 start-page: 463 year: 2006 end-page: 471 article-title: The matrix reorganized: extracellular matrix remodeling and integrin signaling publication-title: Curr Opin Cell Biol – volume: 94 start-page: 5155 year: 2009 end-page: 5162 article-title: Adipose tissue collagen VI in obesity publication-title: J Clin Endocrinol Metab – volume: 278 start-page: E1144 year: 2000 end-page: 1152 article-title: Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women publication-title: Am J Physiol Endocrinol Metab – volume: 106 start-page: 130 year: 2009 end-page: 137 article-title: Cytokines derived from cultured skeletal muscle cells after mechanical strain promote neutrophil chemotaxis publication-title: J Appl Physiol (Bethesda, MD, 1985) – volume: 14 start-page: 227 year: 2008 end-page: 236 article-title: Three‐dimensional primary hepatocyte culture in synthetic self‐assembling peptide hydrogel publication-title: Tissue Eng A – volume: 59 start-page: 2817 year: 2010 end-page: 2825 article-title: Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss publication-title: Diabetes – volume: 20 start-page: 811 year: 2006 end-page: 827 article-title: Cellular mechanotransduction: putting all the pieces together again publication-title: FASEB J Off Publ Fed Am Soc Exp Biol – volume: 35 start-page: 158 year: 2003 end-page: 163 article-title: Culture of human adipose tissue explants leads to profound alteration of adipocyte gene expression publication-title: Horm Metab Res – volume: 26 start-page: 80 year: 2008 end-page: 91 article-title: Connective tissue growth factor: structure–function relationships of a mosaic, multifunctional protein publication-title: Growth Factors Chur – volume: 23 start-page: 11 year: 2009 end-page: 24 article-title: Macrophage‐secreted factors promote a profibrotic phenotype in human preadipocytes publication-title: Mol Endocrinol – volume: 281 start-page: 20608 year: 2006 end-page: 20622 article-title: Mechanical stretch modulates the promoter activity of the profibrotic factor CCN2 through increased actin polymerization and NF‐ B activation publication-title: J Biol Chem – year: 2014 article-title: Association of adipose tissue and liver fibrosis with tissue stiffness in morbid obesity: links with diabetes and BMI loss after gastric bypass publication-title: J Clin Endocrinol Metab – volume: 22 start-page: 5912 year: 2002 end-page: 5922 article-title: 5 1 integrin activates an NF‐ B‐dependent program of gene expression important for angiogenesis and inflammation publication-title: Mol Cell Biol – volume: 147 start-page: 4950 year: 2006 end-page: 4959 article-title: Cathepsin s promotes human preadipocyte differentiation: possible involvement of fibronectin degradation publication-title: Endocrinology – volume: 10 start-page: 75 year: 2009 end-page: 82 article-title: Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus publication-title: Nat Rev Mol Cell Biol – volume: 121 start-page: 2094 year: 2011 end-page: 2101 article-title: Adipose tissue remodeling and obesity publication-title: J Clin Invest – volume: 12 start-page: e494 year: 2011 end-page: 503 article-title: Architecture and the extracellular matrix: the still unappreciated components of the adipose tissue publication-title: Obes Rev Off J Int Assoc Study Obes – volume: 125 start-page: 3061 year: 2012 end-page: 3073 article-title: Mechanosensitive mechanisms in transcriptional regulation publication-title: J Cell Sci – volume: 295 start-page: C740 year: 2008 end-page: 751 article-title: Connective tissue growth factor inhibits adipocyte differentiation publication-title: Am J Physiol Cell Physiol – ident: e_1_2_8_18_1 doi: 10.1210/en.2006-0386 – ident: e_1_2_8_13_1 doi: 10.1111/j.1478-3231.2008.01826.x – ident: e_1_2_8_17_1 doi: 10.1210/me.2008-0183 – ident: e_1_2_8_27_1 doi: 10.1074/jbc.M600214200 – ident: e_1_2_8_8_1 doi: 10.1152/ajpendo.00329.2010 – ident: e_1_2_8_24_1 doi: 10.1038/nrm2594 – ident: e_1_2_8_34_1 doi: 10.1161/01.ATV.18.6.894 – ident: e_1_2_8_20_1 doi: 10.1158/0008-5472.CAN-08-2997 – ident: e_1_2_8_35_1 doi: 10.1152/japplphysiol.90584.2008 – ident: e_1_2_8_40_1 doi: 10.1038/ncb2756 – ident: e_1_2_8_4_1 doi: 10.1172/JCI45887 – ident: e_1_2_8_33_1 doi: 10.1210/jc.2013-3253 – ident: e_1_2_8_3_1 doi: 10.1111/j.1467-789X.2010.00811.x – ident: e_1_2_8_10_1 doi: 10.1128/MCB.01300-08 – ident: e_1_2_8_25_1 doi: 10.1242/jcs.093005 – ident: e_1_2_8_30_1 doi: 10.1101/gad.1664408 – ident: e_1_2_8_2_1 doi: 10.1152/ajpcell.00328.2012 – ident: e_1_2_8_7_1 doi: 10.2337/db10-0585 – ident: e_1_2_8_15_1 doi: 10.1002/art.24620 – ident: e_1_2_8_32_1 doi: 10.1128/MCB.00192-09 – ident: e_1_2_8_16_1 doi: 10.1080/08977190802025602 – ident: e_1_2_8_26_1 doi: 10.1128/MCB.22.16.5912-5922.2002 – ident: e_1_2_8_39_1 doi: 10.1016/j.cell.2009.10.027 – ident: e_1_2_8_23_1 doi: 10.1096/fj.05-5424rev – ident: e_1_2_8_36_1 doi: 10.1152/ajpcell.00333.2007 – ident: e_1_2_8_37_1 doi: 10.1016/j.ceb.2006.08.009 – ident: e_1_2_8_5_1 doi: 10.1186/gb-2008-9-1-r14 – ident: e_1_2_8_38_1 doi: 10.1038/nrm2122 – ident: e_1_2_8_6_1 doi: 10.2337/diabetes.54.8.2277 – ident: e_1_2_8_19_1 – ident: e_1_2_8_11_1 doi: 10.1016/j.cell.2006.02.050 – ident: e_1_2_8_21_1 doi: 10.1055/s-2003-39070 – ident: e_1_2_8_31_1 doi: 10.1152/ajpendo.2000.278.6.E1144 – ident: e_1_2_8_9_1 doi: 10.1210/jc.2009-0947 – ident: e_1_2_8_14_1 doi: 10.1186/1755-1536-5-S1-S24 – ident: e_1_2_8_28_1 doi: 10.1152/physiolgenomics.90291.2008 – ident: e_1_2_8_22_1 doi: 10.1089/tea.2007.0143 – ident: e_1_2_8_12_1 doi: 10.1159/000262316 – ident: e_1_2_8_29_1 doi: 10.1038/nrm3416 |
| SSID | ssj0009955 |
| Score | 2.4587796 |
| Snippet | Fibrosis is a hallmark of human white adipose tissue (WAT) during obesity‐induced chronic inflammation. The functional impact of increased interstitial... Fibrosis is a hallmark of human white adipose tissue ( WAT ) during obesity‐induced chronic inflammation. The functional impact of increased interstitial... Fibrosis is a hallmark of human white adipose tissue (WAT) during obesity-induced chronic inflammation. The functional impact of increased interstitial... |
| SourceID | proquest pubmed crossref wiley istex |
| SourceType | Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 183 |
| SubjectTerms | 3D culture Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism Adipocytes Adipocytes, White - metabolism Adipocytes, White - pathology Adipokines - genetics Adipokines - metabolism Amino Acid Oxidoreductases - genetics Amino Acid Oxidoreductases - metabolism Binding Sites Cell Shape Cells, Cultured Collagen - metabolism Connective Tissue Growth Factor - genetics Connective Tissue Growth Factor - metabolism Fibrosis Gene Expression Regulation Granulocyte Colony-Stimulating Factor - genetics Granulocyte Colony-Stimulating Factor - metabolism human obesity Humans Hydrogels Integrin beta1 - genetics Integrin beta1 - metabolism Interleukin-6 - genetics Interleukin-6 - metabolism Lipolysis Mechanotransduction, Cellular Obesity - genetics Obesity - metabolism Obesity - pathology Obesity - physiopathology Phosphoproteins - genetics Phosphoproteins - metabolism Promoter Regions, Genetic Rodents Time Factors Transcription Factors Transfection |
| Title | Human adipocyte function is impacted by mechanical cues |
| URI | https://api.istex.fr/ark:/67375/WNG-FGZ0LFL9-D/fulltext.pdf https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fpath.4347 https://www.ncbi.nlm.nih.gov/pubmed/24623048 https://www.proquest.com/docview/1524139346 https://www.proquest.com/docview/1525766224 |
| Volume | 233 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3rSxwxEB9EQfql79a1tqRFpF_23NtNsgn9JK3nUVRElEophLwOxHon3h2of70z-xLFQvHbws5mk5lJ5pfH_AKwLpyymeJFGtA7Uu76KlUomkqM9cVohDFUUXLy3r4cHvOfJ-JkAb61uTA1P0S34EY9oxqvqYNbN928Iw2lG3t7vOCUSU5ntQgQHd5RR2ktRMcUzvtlyyqU5Zvdl_di0RKp9eoxoHkft1aBZ_AC_rRVrs-bnPXmM9fzNw_YHJ_YppfwvAGkbKv2oFewEMevYXmv2XJ_A2W1zM9sOL2Y-OtZZBQJyZrsdMrqHMsYmLtm55GSiMnmzGPD3sLxYPvo-zBtbltIPRdlmXqZ0VwyCMejly63FiO_CCKGfuaUzr0e-WxkNYYzbfNqrOA4d0R8EaVAixbvYHE8GccVYE7JEEpXaiyKR-2wqMwitFDC4vDQDwl8bfVufENFTjdi_DU1iXJuSBGGFJHAl070oubfeExoozJeJ2Evz-jAWinMr_0dM9j5ne0OdrX5kcBaa13T9NWpQQSDkVwXXCbwuXuNvYy2Tuw4TuaVDE7MJOKdBN7XXtH9LOeSVtYVtqqy7b_raQ62job0sPr_oh_gGWI0Xp9OW4PF2eU8fkQcNHOfKoe_BTgVAQU |
| linkProvider | Wiley-Blackwell |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3daxQxEB9qC9oXv7WrVaOI-LLXvd0km4AvxXo99e4QuWIRJOTroFTvSnsH1r_emf0qlQri28LOZpPMTOaXSfILwEvhlM0UL9KA1pFy11epQtFUYqwvZjOMoYoOJ48ncnjAPxyKwzV4056FqfkhuoQbeUY1XpODU0J654I1lK7s7fGCl9dgg270Jub8vc8X5FFaC9FxhfN-2fIKZflO9-mlaLRBHfvzKqh5GblWoWdwC761la53nBz3VkvX87_-4HP831bdhpsNJmW7tRHdgbU4vwvXx82q-z0oq0w_s-HoZOHPl5FRMCSFsqMzVh-zjIG5c_Yj0jliUjvz2LL7cDB4N307TJsLF1LPRVmmXmY0nQzC8eily63F4C-CiKGfOaVzr2c-m1mNEU3bvBouOE4fEWJEKVCpxQNYny_mcQuYUzKE0pUai-JROywqs4gulLA4QvRDAq_bjje-YSOnSzG-m5pHOTfUEYY6IoEXnehJTcFxldCrSnudhD09pj1rpTBfJvtmsP81Gw1G2uwlsN2q1zTuemYQxGAw1wWXCTzvXqOj0eqJncfFqpLBuZlEyJPAw9osup_lXFJyXWGrKuX-vZ7m0-50SA-P_l30GdwYTscjM3o_-fgYNhGy8Xqz2jasL09X8QnCoqV7Wln_b0aKBSE |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3raxQxEB9qC8Uvvh-rVVcR8cte93aTbIKfiuf21OtRpMVShJDXQqneHe0dWP96Z_ZVKhXEbws7m01mJplfHvMLwGtupUklyxOP3pEwO5SJRNFEYKzPqwpjqKTk5L2pGB-yT0f8aA3edbkwDT9Ev-BGPaMer6mDL3y1fUkaSjf2DljOihuwwUSq6N6G0ZdL7iilOO-pwtmw6GiF0my7__RKMNogvf68DmleBa515Clvw7euzs2Bk9PBamkH7tcfdI7_2ag7cKtFpPFO40J3YS3M7sHmXrvnfh-Kep0_Nv5kMXcXyxBTKCRzxifncZNkGXxsL-IfgbKIyeixw4Y9gMPyw8H7cdJet5A4xosicSKlyaTnlgUnbGYMhn7uefDD1EqVOVW5tDIK45kyWT1YMJw8IsAIgqNJ84ewPpvPwmOIrRTeF7ZQWBQLymJRqUFsIbnB8WHoI3jb6V27loucrsT4rhsW5UyTIjQpIoJXveiiIeC4TuhNbbxewpyd0om1guuv011d7h6nk3Ki9CiCrc66uu2s5xohDIZylTMRwcv-NXYz2jsxszBf1TI4MxMIeCJ41HhF_7OMCVpal9iq2rZ_r6fe3zkY08OTfxd9AZv7o1JPPk4_P4WbiNdYc1JtC9aXZ6vwDDHR0j6vff83MykD0A |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Human+adipocyte+function+is+impacted+by+mechanical+cues&rft.jtitle=The+Journal+of+pathology&rft.au=Pellegrinelli%2C+V&rft.au=Heuvingh%2C+J&rft.au=du+Roure%2C+O&rft.au=Rouault%2C+C&rft.date=2014-06-01&rft.pub=John+Wiley+%26+Sons%2C+Ltd&rft.issn=0022-3417&rft.eissn=1096-9896&rft.volume=233&rft.issue=2&rft.spage=183&rft.epage=195&rft_id=info:doi/10.1002%2Fpath.4347&rft.externalDBID=10.1002%252Fpath.4347&rft.externalDocID=PATH4347 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0022-3417&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0022-3417&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0022-3417&client=summon |